| Late-Breaking Abstracts |
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| 2022年7月2日 11:00～12:00 沖縄コンベンションセンター 展示棟 ポスター会場1
3LBA-037
糖尿病モデルマウスにおける胎児期の自律神経活動評価
Evaluation of autonomic nervous function during fetal stage in diabetes model mice
*笠原 好之(1)、吉田 千尋(1)、木村 芳孝(1)、齋藤 昌利(1)
1. 東北大学大学院医学系研究科
*Yoshiyuki Kasahara(1), Chihiro Yoshida(1), Yoshitaka Kimura(1), Masatoshi Saito(1)
1. Grad Sch Med, Tohoku Univ, Sendai, Japan
Keyword: diabetes, fetal ECG, autonomic nervous system, model mice
Type 2 diabetes is a lifestyle-related disease that causes a variety of diseases such as cerebrovascular and cardiovascular diseases, etc. Although abnormal autonomic nervous system function has been shown to be one of the characteristics of type 2 diabetes, details of when and how changes in autonomic function occur in the high-risk group for type 2 diabetes are not clear. Since the maternal environment and fetal development during the fetal period are known to strongly influence the future disease vulnerability of the fetus, in this study, we evaluated autonomic nervous system activity during fetal period using db mice with mutations in the leptin receptor gene. db mutant mice are known to develop type 2 diabetes after adulthood. Male and female mice with heterozygous db gene were crossed to obtain fetuses of all genotypes, and whether vulnerability to future diabetes could be detected as changes in fetal autonomic activity. To assess fetal autonomic nervous system activity, we used the fetal electrocardiogram (ECG) measurement technique which we developed. By analyzing the power spectrum of the heart rate variability obtained by ECG measurements, high-frequency (HF) and low-frequency (LF) components can be calculated. The HF represents parasympathetic nervous activity, while the LF represents sympathetic and parasympathetic nervous activity; LF/HF represents sympathetic nervous activity. Fetal ECGs of mice of each db genotype were measured to evaluate heart rate, short term variability of heart rate, LF, HF and LF/HF in fetal mice. In this results, there were no difference in these values by db genotype. Thus, at least in the fetal period, there were no changes in autonomic nervous system activity, even in db deficient mice, which are considered to be at high risk for type 2 diabetes. In the future, we plan to examine the hypothesis that more pronounced vulnerability is revealed when pregnant mice are subjected to a nutritional challenge by feeding them a high-fat diet. | | 2022年7月2日 11:00～12:00 沖縄コンベンションセンター 展示棟 ポスター会場1
3LBA-038
TREK作動薬を投与した卵巣摘出ラットにおけるエストラジオールの体温調節反応への影響
Effect of estradiol on thermoregulatory responses in ovariectomized rats administrated TREK agonist
*内田 有希(1)、上條 翔太郎(2)、本間 元康(1)、政岡 ゆり(1)、泉﨑 雅彦(1)
1. 昭和大学医学部生理学講座生体調節機能学部門、2. 昭和大学薬学部基礎医療薬学講座生理学部門
*Yuki Uchida(1), Shotaro Kamijo(2), Motoyasu Honma(1), Yuri Masaoka(1), Masahiko Izumizaki(1)
1. Department of Physiology, Showa University School of Medicine, Shinagawa, Tokyo, Japan, 2. Division of Physiology, Toxicology and Therapeutics, Department of Pharmacology, Showa University, Shinagawa, Tokyo, Japan
Keyword: estradiol, TREK, thermoregulation, cold receptor
INTRODUCTION TWIK-related potassium channels (TREK) have been reported to be new cold receptors. TREK channels are present in sensory neurons with other cold receptors, such as transient receptor potential melastatin 8. We reported that estradiol (E2), one of female hormones, affected thermoregulation in ovariectomized rats via transient receptor potential melastatin 8; however, the effect of E2 on thermoregulatory responses via TREK has not been elucidated. METHODS Ovariectomized rats were implanted a silastic tube with or without E2 (22.3mg) underneath the dorsal skin (E2(+) and E2(−) groups) and data logger (nano tagⓇ, Kissei Comtec) for body temperature (Tb) measurement into peritoneal cavity. After 1 week of recovery, on the day of the experiment, the rats were administered a TREK agonist (Ostruthin Imperatorin, 4.2μg) or vehicle intraperitoneally at 10:00, and measured Tb, activity, skin temperature of the tail (Ttail), and thermoregulatory behavior evaluated by hiding behavior of the tail (Uchida et al., 2012, J Comp Physiol A 198:89-95) for 2 hours at 27ºC. After the experiment, blood was collected, and plasma catecholamine, triiodothyronine, and thyroxine were measured. RESULTS Ostruthin increased Tb in the E2(+) group; however, decreased in the E2(−) group. In the ostruthin group, Tb in the E2(+) group was higher than that in the E2(−) group. Ostruthin did not affect Ttail in the E2(+) group; however, decreased Ttail in the E2(−) group. No significant differences were observed in the activity, duration, onset of tail hiding behavior, plasma catecholamine, triiodothyronine, or thyroxine among the groups. CONCLUSION E2 could increase Tb via TREK channels; however, the activity, Ttail, plasma catecholamine, triiodothyronine, and thyroxine could not affect the response. | | 2022年7月2日 11:00～12:00 沖縄コンベンションセンター 展示棟 ポスター会場1
3LBA-039
タウ/MAP2二重欠損マウスが呈する育児行動障害に対するオキシトシンの効果
Oxytocin rescues maternal childcare behavior dysfunctions in tau/MAP2 double deficient mice
*宮坂 知宏(1,3)、謝 策(1)、上田 晃樹(1)、矢口 花紗音(1)、植田 結稀(1)、佐久間 浩平(1)、堀部 麻子 (1)、原田 彰宏(2)
1. 同志社大学生命医科学部、2. 大阪大学医学系研究科、3. 同志社大学神経変性疾患研究センター
*Tomohiro Miyasaka(1,3), Xie Ce(1), Koki Ueda(1), Kasane Yaguchi(1), Yuki Ueda(1), Kohei Sakuma(1), Asako Horibe(1), Akihiro Harada(2)
1. Faculty of Life and Med Sci, Doshisha Univ, Kyoto, Japan, 2. Grad Sch Med, Osaka Univ, Osaka, Japan, 3. Cent for Res in Neurodegenerative Diseases, Doshisha Univ, Kyoto, Japan
Keyword: Microtubule associated protein, tau, MAP2, oxytocin
Tau/MAP2 family genes, a classical group of microtubule associated proteins (MAPs), are paralog emerged from vertebrate and highly conserved beyond species respectively. Tau and MAP2 proteins are expressed exclusively in nervous system and have functions to promote microtubule assembly and stabilize them. Interestingly, they exhibit a characteristic subcellular compartmentalization, with tau predominantly localized in axon and MAP2 being somatodendritic. No life-threatening abnormalities have been reported in mice deficient in Mapt or Map2 alone. However, they may complementally have a role to unknown biological functions that this family genes should be responsible for. To learn the functional significance of tau/MAP2 family genes, here we developed double knockout (DKO) mice which lack both of Mapt and Map2 genes. Although, Tau/MAP2 DKO mice have born low ratio within siblings than other genotypes, developed without particular developmental anomaly. DKO mice were fertile, however females could not care newborns. This was not found in wild-type and each single gene KO mice. Expression analysis indicated that oxytocin gene expression was reduced only in DKO. Because the oxytocin have been known to responsible for postpartum maternal behaviors, we addressed whether the oxytocin administration improve the behavior of DKO mice. Intranasal administration of oxytocin to peripartum DKO mother mice significantly enhanced nesting, nursing, and retrieving behaviors, and prolonged childcare period. Why do tau and MAP2 act complementarily to the maintenance of oxytocin secretory function despite these distinct intraneuronal distributions? Histopathological analyses revealed that the MAP2 deficient reduced the excitability of oxytocin neurons that can be probed by impaired c-fos staining. On the other hand, tau deficient mice showed the accumulation of oxytocin, which may be caused by the obstruction of axonal transport, in cell body of the neurons. DKO mice showed the phenotype having both of these disabilities, low excitability and reduced axonal transport, in oxytocin neurons. These data suggested that the tau/MAP2 family genes are essential for childcare behavior of mammalian via oxytocin endocrine system. Furthermore, given the distinct distribution of these MAPs, it can be considered that this is an example of indirect complementation to a single biological function by a set of paralog gene products. | | 2022年7月2日 11:00～12:00 沖縄コンベンションセンター 展示棟 ポスター会場1
3LBA-040
カンナビノイドCB2受容体の持つ二面性：レプチンシグナリングを介した末梢神経炎症調節機構に対する影響を中心に
Cannabinoid CB2 receptors have double-side role to the peripheral neuroinflammation: The contribution of leptin signaling
*野崎 千尋(1)、Astrid Markert(2)、柴田 重信(1)、Andreas Zimmer(2)
1. 早稲田大学先進理工学部
*Chihiro Nozaki(1), Astrid Markert(2), Shigenobu Shibata(1), Andreas Zimmer(2)
1. Sch Adv Aci Eng, Waseda university, Tokyo, Japan, 2. Institute of Molecular Psychiatry, University of Bonn, Bonn, Germany
Keyword: Neuroinflammation, CB2 receptors, Leptin signaling, Pain
It is widely known that cannabinoid type 2 (CB2) receptor deficiency enhances neuroinflammation and pain development in the animal model of nerve injury-evoked neuropathic pain. We previously proposed the upregulated leptin signaling at the peripheral nerve as one of the underlying molecular mechanism, as nerve-injured CB2 knockouts displayed robust upregulation of leptin receptors in both injured and non-injured nerve tissue. Those leptin receptors seemed to be expressed on the macrophages which is recruited to the nerve by the tissue injury, indicating the infiltration of leptin receptor-expressing macrophages. Thus, Due to these past results we also hypothesized that lack of CB2 receptor might also enhance the high fat diet (HFD)-induced peripheral neuroinflammation. However, surprisingly, CB2 receptor knockout animals showed the significant resistance to the HFD-induced neuroinflammation. Namely, 5-week feeding of HFD induced substantial hypersensitivity in WT animals, while tactile sensitivity of HFD-fed CB2 knockouts remained intact. In the same animals, we further found the significant upregulation of 1) leptin receptor expression, 2) infiltrated macrophages, 3) chemokine receptor CXCR4 expression, all in peripheral sciatic nerve of HFD-fed WT animals, but not in HFD-fed CB2 knockout mice, as well as standard fat diet (SFD)-fed WT and CB2-knockout controls. Moreover, we also confirmed that leptin receptor deficient animals do not display any hypersensitivity, macrophage infiltration or CXCR4 upregulation in the nerve after the 5-week HFD feeding, suggesting that leptin receptor activation might be one of the upstream key modulators of the HFD-evoked peripheral inflammatory responses. These results together with past examination in the neuropathic pain model suggest that leptin signaling takes major role in the peripheral neuroinflammation development, no matter how inflammation has been evoked. Furthermore, we will propose that CB2 receptors might have the double-sided regulatory role on the leptin signaling by the modulation of leptin receptor expression on the peripheral nerves, to in the end enhance or inhibit the development of neuroinflammation. | | 2022年7月2日 11:00～12:00 沖縄コンベンションセンター 展示棟 ポスター会場1
3LBA-041
神経ペプチドを介した繁殖期依存的な摂食行動の調節機構
Peptidergic neuromodulatory mechanisms for feeding behavior dependent on the reproductive status
*田杭 夕里佳(1)、武田 進吾(1)、和井田 洋世(1)、木村 智貴(2)、神田 真司(3)、武田 洋幸(1)、岡 良隆(1)、馬谷 千恵(1)
1. 東京大学理学系研究科 生物科学専攻、2. 東京大学工学系研究科、3. 東京大学大気海洋研究所
*Yurika Tagui(1), Shingo Takeda(1), Hiroyo Waida(1), Tomoki Kimura(2), Shinji Kanda(3), Hiroyuki Takeda(1), Yoshitaka Oka(1), Chie Umatani(1)
1. Dept Biol Sci, Grad Sch Sci, Univ of Tokyo, Tokyo, Japan, 2. Grad Sch Eng, Univ of Tokyo, Tokyo, Japan, 3. AORI, Univ of Tokyo, Tokyo, Japan
Keyword: feeding behavior, reproduction, neuropeptide
Reproduction and feeding behavior are reported to be correlated with each other, since energy balance was shown to regulate reproductive status (Kauffmann & Rissman, 2004, Hasebe et al., 2016). However, the regulatory mechanisms for feeding behavior dependent on the reproductive status are still unknown. One possible reason is that most of the conventional model animals for such studies do not breed seasonally. Here, we used a teleost medaka, which has advantages for the study of such regulatory mechanisms. Female medaka in reproductive status eat more than those in non-reproductive status (Waida, master’s thesis, 2015). Furthermore, medaka is a seasonal breeder, whose reproductive status can be experimentally controlled by day length (long day (LD): reproductive, short day (SD): non-reproductive). We first conducted whole-brain RNA-sequencing of LD/SD female fish. Among the conventional candidate feeding-related neuropeptides, we identified two kinds of neuropeptides, agouti-related peptide 1 (AgRP1) and neuropeptide Y b (NPYb), both of which showed higher expressions in LD than in SD. Likewise, whole brain RT-qPCR showed that LD fish expressed higher levels of both agrp1 and npyb than the SD fish. On the other hand, fasting for two weeks increased the expression of agrp1 but decreased that of npyb, suggesting that the two peptides are involved in feeding in different manners. Next, to examine which of the two factors, LD-induced sexual maturity or day length, regulates the expressions of the two genes, we used immature juvenile fish and compared their expressions under LD/SD conditions. Here, neither of these genes showed significant difference in the expression levels between LD and SD, suggesting that neither of them is regulated directly by day length. Therefore, to confirm the effect of sexual maturity, we analyzed expression of the two genes in ovariectomized fish (OVX, fish with surgical ablation of the ovary) and compared with that in sham-operated fish (Sham). The OVX fish showed lower agrp1 expression than Sham, while there was no significant difference in npyb expression. Furthermore, the administration of 17β-Estradiol (E2, an ovarian estrogen) to OVX fish increased the expression of agrp1 but not of npyb. We here propose that high E2 level in reproductive status increases the expression of agrp1, which results in facilitation of feeding behavior, whereas the expression level of npyb may simply reflect the nutritional status of the fish. | | 2022年7月2日 11:00～12:00 沖縄コンベンションセンター 展示棟 ポスター会場1
3LBA-042
CRF neurons in the amygdala and IPACL promote wakefulness in mice
*コウ ケイエイ(1,2)、Sheikh Mizanur Rahaman1(1,2)、Noriaki Fukatsu(2,3)、Akihiro Yamanaka(1,2)、Daisuke Ono(1,2)
1. 名古屋大学環境医学研究所、2. 名古屋大学大学院医学系研究科
*chijung hung(1,2), Sheikh Mizanur Rahaman1(1,2), Noriaki Fukatsu(2,3), Akihiro Yamanaka(1,2), Daisuke Ono(1,2)
1. Nagoya U research institute of environment medicine , 2. Nagoya U graduate school of medicine, 3. Department of Systems Biology, Nagoya University Graduate School of Medicine, Nagoya, Japan
Keyword: CRF, sleep, amygdala
Sleep and wakefulness are regulated by several factors, such as stress, physiological illness or environmental noise. Among them, the proportion of insomnia caused by stresses is more than 25%. In our brain, a neuropeptide, corticotropin-releasing factor (CRF) peptide, is involved in stress responses for resisting stress. Previously, we reported that CRF neurons in the paraventricular nucleus (PVN) are contributed to the regulation of wakefulness. Especially, circadian clock-controlled wakefulness is regulated by CRF neurons in the PVN (Ono et al., 2020). Beside the PVN, CRF producing neurons also present in the other brain areas, such as piriform cortex, inferior olivary nucleus bed nucleus of the stria terminalis (BNST), lateral part of the interstitial nucleus of the anterior commissure (IPACL) and amygdala. However, it is unclear whether CRF neurons in these areas are involved in sleep regulation. We firstly focused on CRF neurons in IPACL and amygdala because these two areas are participating in negative emotion, and they may have an influence on sleep. To understand the functional role of CRF neurons in the amygdala and IPACL in sleep and wakefulness, we expressed hM3Dq or hM4Di in CRF neurons in these areas by virus injection and measured electroencephalography (EEG) and electromyography (EMG) to assess vigilant state in theses mice. Activation of CRF neuron in IPACL and amygdala by injection of clozapine N-oxide increased time in wakefulness. Whereas inhibition of these neurons attenuated time in wakefulness. These results indicate that CRF neurons in the amygdala and IPACL play a role in the regulation of wakefulness in mice. | | 2022年7月2日 11:00～12:00 沖縄コンベンションセンター 展示棟 ポスター会場1
3LBA-043
マウスの睡眠覚醒制御におけるSleepy2 familyの役割
The role of Sleepy2 family in sleep/wake regulation in mice
*塚本 拓実(1)、金 慈暻(1)、浅間 のどか(1)、浅野 冬樹(1)、藤山 知之(1)、一久 綾(1)、堀田 範子(1)、海老原 恭美(1)、三好 千香(1)、船戸 弘正(1,2)、柳沢 正史(1,3,4)
1. 筑波大学国際統合睡眠医科学研究機構、2. 東邦大学医学部
*Takumi Tsukamoto(1), Staci Jakyong Kim(1), Nodoka Asama(1), Fuyuki Asano(1), Tomoyuki Fujiyama(1), Aya Ikkyu(1), Noriko Hotta Hirashima(1), Kumi Ebihara(1), Chika Miyoshi(1), Hiromasa Funato(1,2), Masashi Yanagisawa(1,3,4)
1. International Institute for Integrative Sleep Medicine, University of Tsukuba , 2. Dept. of Anatomy, Fac. of Med., Toho Univ., Tokyo Japan, 3. Life Sci. Center, Tsukuba Advanced Res. Alliance, Univ. of Tsukuba, Ibaraki, Japan, 4. Dept. of Mol. Genet., Univ. of Texas Southwestern Med. Ctr., Dallas, TX
Keyword: Sleepy2 family, phosphodeficient mice, sleep/wake behavior
Although sleep plays a crucial role in maintaining mental and physical health of animals, the molecular and cellular mechanisms regulating sleep behavior remain unknown. Through a large-scale forward genetic approach, our laboratory established the Sleepy and Sleepy2 mutant pedigrees showing increase in both non-REM sleep (NREMS) time and NREMS EEG slow-wave (delta) power. The Sleepy mutant mice have a gain-of-function mutation in the salt inducible kinase 3 (Sik3) gene, and Sleepy2 mutant mice have a loss-of-function mutation. Importantly, another Sleepy2 family member may also be involved in sleep/wake regulation. Here, we examine the role of the Sleepy2 family member using phosphodeficient mice. We established phosphodeficient mouse lines using the CRISPR/Cas9 technology and adult male mice at age of 8-10 weeks were subjected to EEG/EMG implant surgery for sleep/wake behavior analysis. As a result, phosphodeficient mice in the Sleepy2 family member showed increased wake time and reduced NREMS delta power, compared to WT littermate controls. It suggests that not only Sleepy2 but also another Sleepy2 family member have crucial role in sleep/wake regulation. There have been many recent advances in understanding the neuronal circuitry switching sleep/wake states. However, little is still known about the intracellular signaling components sensing the changes in sleep need and driving the switch between sleep and wakefulness. Identification of Sleepy2 and its family members as key components in sleep/wake regulation will advance our understanding of the neuronal substrate for sleep need. | | 2022年7月2日 11:00～12:00 沖縄コンベンションセンター 展示棟 ポスター会場1
3LBA-044
サル外側腕傍核における情動と認知行動の神経表現
Neuronal representation of emotion and cognition in the monkey lateral parabrachial nucleus
*安田 正治(1)、中村 加枝(1)
1. 関西医科大学生理学講座
*Masaharu Yasuda(1), Kae Nakamura(1)
1. Kansai Medical University
Keyword: monkey, emotion, cognition, lateral parabrachial nucleus
Environments induce emotional- and body- state changes, which may lead to modulation in the cognitive processes. Human brain imaging studies report the correlation between the activity of brain areas representing inner body state and emotional experience/cognitive performance. However, the detailed neuronal mechanisms of these processes are elusive. The lateral parabrachial nucleus (LPBN) receives ascending sensory inputs from the spinal cord and the nucleus of the solitary tract. The LPBN then relays the information to the forebrain that is implicated in an affective and cognitive behavior. LPBN is also involved in fear learning by signaling noxious cutaneous and visceral stimuli. We thus hypothesized that the LPBN provides sensory signals for integrative emotional and behavioral processing. To characterize the detailed information carried by the LPBN, we recorded the single- neuronal activity in the LPBN while the monkey performed a cognitive task under positive or negative emotional conditions. First, we subjected a monkey to liquid reward and aversive air-puff conditioning by presenting two different visual stimuli (CSs). We then had a monkey perform a reversal choice task. In the task, after the central fixation, two choice cues were presented on the left and right. The monkey chose one of them by making a saccade, followed by a reward for one, or no reward for the other. The cue-reward association reversed at 80% of the correct choice rate. During the inter-trial interval, one of the appetitive or aversive CSs was briefly presented until the reversal occurred. This procedure allowed us to investigate neuronal correlate of cognitive task performance under distinct emotional contexts, verified by the modulation of autonomic responses: larger pupil diameter and larger high/low-frequency ratio in the variability of pulsation, the beating of blood, for the aversive CS. Many LPBM showed excitatory responses to a freely given liquid reward. In the conditioning, LPBN neurons preferentially responded to either one of appetitive or aversive CSs suggesting the responses to learned stimuli. During the choice task, a group of neurons exhibited modulation in activity depending on the upcoming choice before the presentation of choice cues but differently depending on the appetitive/aversive conditions. These data suggest that the LPBN is involved in appetitive or aversive emotional responses as well as behavioral responses under different emotional contexts. | | 2022年7月2日 11:00～12:00 沖縄コンベンションセンター 展示棟 ポスター会場1
3LBA-045
Force-gated mechanosensitive ion channels for magnetogenetic control of neuronal activities
*Chanhyun Park(1), Sunmi Lee(1), Yuko Ambo(1), Taekyu Oh(1,2), Jung-uk Lee(1), Jae-hyun Lee(1,2), Jinwoo Cheon(1,2)
1. Center for Nanomedicine, Institute for Basic Science, Seoul, Korea, 2. Grad Program of NanoBME, Advanced Science Institute, Yonsei Univ, Seoul, Korea
Keyword: Neuromodulation, Magnetogenetics, Nanobiotechnology
Modulation of neuronal activity in the genetically specified neurons has been a long sought-after goal for many scientists. This sort of manipulation has important implications for both basic and clinical neuroscience as it provides a way for scientists to directly probe into how the brain works to support the various cognitive processes. Newly developed neuromodulation tools such as optical stimulation with genetic manipulations have shown their effectiveness yet the limitations persist due to the invasiveness from surgical implantation of devices. We recently have suggested magnetism, in combination with magnetic nanoparticles and genetically engineered mechanosensitive ion channels, as a way to achieve non-invasive and remote modulation of specific neuronal population located at particular brain region. We addressed and resolved issues related with previous magnetogenetics regarding to the physical limitation of nanoparticles and magnetism. One key advantage of this magnetogenetics technology is that it does not require permanent implantation of invasive electrodes or optical fibers. Another benefit is that magnetism can penetrate into the deeper regions of the brain, thus less-invasive neuromodulation can be achieved. By mimicking magnetoreception in nature, we overcame previous limitations in force generation and achieved magneto-mechanical modulation of genetically engineered mechanosensitive ion channels in vivo. Further possibilities for advanced application of this technology will be discussed. | | 2022年7月2日 11:00～12:00 沖縄コンベンションセンター 展示棟 ポスター会場1
3LBA-046
手指運動課題におけるNegative BOLD responseの空間的・時間的特性
Regional and temporal characteristics of the Negative BOLD response during hand grasp task
*笠原 和美(1,2)、釣木澤 朋和(1)
1. 国立研究開発法人 産業技術総合研究所
*Kazumi Kasahara(1,2), Tomokazu Tsurugizawa(1)
1. National Institute of Advanced Industrial Science and Technology, 2. FOREST, JST
Keyword: Blood oxygenation level-dependent , Negative BOLD, fMRI
Functional MRI (fMRI) is widely used to investigate non-invasively the neuronal activation by measuring blood oxygenation level-dependent (BOLD) response, which relies on neurovascular coupling. The conventional hemodynamic response function used to calculate the BOLD signal change in a specific brain region is based on the intimate coupling between neural excitation and vasculature and neural inhibition is not considered. However, a negative BOLD response is often observed in addition to a positive BOLD response. The negative BOLD is hypothesized to be derived from a neural inhibition, but the mechanism has not been elucidated.
In the present study, using fMRI with 3T MRI system, positive and negative BOLD responses were investigated during simple hand grasp tasks in healthy subjects. To assess the characteristic of the time-course of negative BOLD response, three types of task and rest periods were used, 30 sec task-30 sec rest, 15 sec task-45 sec rest, and 60 sec task-60 sec rest, respectively.
Negative BOLD responses were observed in the medial orbitofrontal cortex and the precuneus-posterior cingulate cortex, which are associated with the default mode network (DMN), and in the contralateral motor cortex, which is associated with interhemispheric neuronal inhibition. Furthermore, negative BOLD response in the posterior part of the posterior ipsilateral motor cortex was also observed, and a positive BOLD response was observed in the anterior part of the posterior ipsilateral motor cortex. The BOLD signals in the medial orbitofrontal cortex and the precuneus-posterior cingulate cortex were decreased from the start of the motion, whereas the BOLD signal in the contralateral motor area and its posterior region were decreased gradually following the positive signal change. Furthermore, the negative BOLD response was suppressed with a short rest duration (30 sec), although the positive BOLD response was not affected.
The present study shows that the time-courses of the negative BOLD responses in DMN-related regions and motor cortex-related areas are different, indicating regional characteristics of the negative BOLD response. Furthermore, the negative BOLD response depends on the duration of the rest period, indicating that the negative BOLD response may require longer recovery time rather than the positive BOLD response. These results suggest that involvement of the inhibited neural activity and decreased blood inflow/outflow may depend on the brain regions and vascular structure. | | 2022年7月2日 11:00～12:00 沖縄コンベンションセンター 展示棟 ポスター会場1
3LBA-047
脳機能超音波イメージングによる覚醒マウスの広域・高解像度な安静時脳ネットワークマッピング
Brain-wide and high-resolution mapping of resting-state networks in awake mice using functional ultrasound imaging
*疋島 啓吾(1,2)、釣木澤 朋和(3)、笠原 和美(3)、高木 亮(1)、葭仲 潔(1)、新田 尚隆(1)
1. 産総研・健康医工学、2. 沖縄科学技術大院、3. 産総研・人間情報インタラクション
*Keigo Hikishima(1,2), Tomokazu Tsurugizawa(3), Kazumi Kasahara(3), Ryo Takagi(1), Kiyoshi Yoshinaka(1), Naotaka Nitta(1)
1. AIST, 2. OIST, 3. AIST
Keyword: Functional ultrasound imaging, Resting state network, MRI
Functional ultrasound imaging (fUS) is a method to visualize neuronal activity in brain-wide regions based on neurovascular coupling by analyzing the high spatiotemporal resolution vasculature images. In resting-state brain activity, low-frequency fluctuations can be measured by MRI to estimate resting-state networks (RSNs) using independent component analysis (ICA), which is an important method for studying disease specific brain network. There have been no reports of RSNs observed in the deep and wide regions of the brain except by MRI. In this study, the fUS was conducted with an in-plane resolution of 50×100μm and a temporal resolution of 100μsec in the resting state of head-restrained awake mice, and high-resolution RSNs in the brain-wide regions were mapped using ICA. The RSNs obtained by fUS were validated from the resting-state fMRI of head-restrained awake mice using an 11.7 tesla MRI with a cryogenic coil. As the results of RSNs by fUS, it allowed us to observe multiple inter-hemispheric homotopic connectivity patterns over brain-wide regions including in the limbic, motor and parietal cortex, caudate putamen, thalamus, superior colliculus, hippocampus and cerebellum. Each distribution of these regions was consistent with the RSNs obtained by MRI. On the other hand, some regions, such as the auditory cortex, could not be observed in the MRI experiments of awake mice. This study demonstrated that resting-state fUS (rs-fUS) can reliably depict brain-wide RSNs distributions. In addition, rs-fUS was able to depict more detailed RSN features than could be obtained by MRI due to the high spatial resolution of fUS. Since fUS has attractive features for studying brain function at the system level because it is easy to perform simultaneous imaging with multimodality (e.g. electrophysiology) and is suitable for imaging during behavioral experiments (e.g. free-moving), rs-fUS is expected to contribute to the elucidation of the biological basis of RSNs in the future. | | 2022年7月2日 11:00～12:00 沖縄コンベンションセンター 展示棟 ポスター会場1
3LBA-048
(17)O-MRIによる脳内の水代謝マッピング
Whole brain mapping of water metabolism using (17)O-MRI in mice
*小牧 裕司(1,2)、亀田 浩之(3)、松本 圭史(1)、関 布美子(1,2)、岡野 栄之(2)、工藤 與亮(3)
1. 公益財団法人実験動物中央研究所、2. 慶應義塾大学、3. 北海道大学
*Yuji Komaki(1,2), Hiroyuki Kameda(3), Yoshifumi Matsumoto(1), Fumiko Seki(1,2), Hideyuki Okano(2), Kohsuke Kudo(3)
1. Central Institute for Experimental Animals, 2. Keio University, 3. Hokkaido University
Keyword: MRI, glymphatic system, water biology
Water containing 17O, a stable isotope of oxygen, have been used as a negative contrast agent in MRI. 17O-water is one of the reagents that have attracted much attention in recent years, as GLP studies and human phase I trials have already demonstrated. Water metabolism in the brain is known as the glymphatic system and is thought to be involved in pathological mechanisms such as Alzheimer's disease. In this experiment, we used 7T MRI to observe the dynamics of 17O-water injected into the cisterna magna of normal mice.
First, we examined the injection pressure when administering 17O water to cisterna magna. The injection conditions were 1.5 μL/min and 0.5 μL/min, and the dose was 10 μL. In previous reports, 1.5 μL/min was considered to maintain physiologically normal conditions with no change in brain pressure. In the present observation, using MRI with 1.5 μL/min of 17O water, enlarged ventricles were observed and unnatural signal increase in the lateral/third ventricle was observed. This phenomenon may have been overlooked in observations using Gd contrast, a conventional positive contrast agent, because the method used was to observe the signal increase due to administration of the contrast agent. Dosing at an infusion rate of 0.5 μL/min was a normal physiological state without observing these abnormalities.
Next, we used two types of anesthesia (Isoflurane/Medetomidine) to observe changes in water metabolism in the brain. Isoflurane-anesthetized mice showed restricted water movement from the cisterna magna to the brain parenchyma. The dilatation of blood vessels and inhibition of respiration by Isoflurane were thought to inhibit water metabolism. In medetomidine-anesthetized mice, moving water into the brain parenchyma and drainage into the nasal turbinates were observed.
We were able to establish mapping of water metabolism in the whole mouse brain using 17O-MRI. In the future, we intend to test the usefulness of this method in Alzheimer's disease and hydrocephalus models, which are known to have abnormalities in water metabolism. | | 2022年7月2日 11:00～12:00 沖縄コンベンションセンター 展示棟 ポスター会場1
3LBA-049
Bdnf-Luciferaseトランスジェニックマウスを用いたin vivo発光イメージングにおけるD-ルシフェリンおよびその類似化合物の比較
Comparison of D-luciferin and its analogues for in vivo bioluminescence imaging using Bdnf-Luciferaase transgenic mouse
*福地 守(1)、三反崎 聖(1)、森屋 亮平(2,3,4)、北田 昇雄(2)、牧 昌次郎(2)、和泉 宏謙(5)、森 寿(5)
1. 高崎健康福祉大学、2. 電気通信大学、3. 東京薬科大学、4. 日本女子大学、5. 富山大学
*Mamoru Fukuchi(1), Satoru Mitazaki(1), Ryohei Moriya(2,3,4), Nobuo Kitada(2), Shojiro Maki(2), Hironori Izumi(5), Hisashi Mori(5)
1. Takasaki Univ of Hlth & Welfare, Gunma, Japan, 2. Univ of Electro-Commun, Tokyo, Japan, 3. Tokyo Univ of Pharm & Life Sci, Tokyo, Japan, 4. Japan Women’s Univ, Tokyo, Japan, 5. Univ of Toyama, Toyama, Japan
Keyword: BDNF, Bioluminescence imaging, Luciferase, Luciferin
Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, plays a crucial role in expressing numerous brain functions including memory consolidation. In addition, the expression of BDNF is detected in the peripheral tissues and organs, suggesting the physiological and pathophysiological roles in these tissues and organs. Previously, we generated a transgenic mouse strain, Bdnf-Luciferase transgenic (Bdnf-Luc Tg) mouse, to visualize changes in Bdnf expression by bioluminescence imaging (BLI). We successfully visualized the activity-dependent Bdnf induction in living mouse brains by an analogue of D-luciferin, TokeOni, which could be distributed to the brain and produce near-infrared bioluminescence. During in vivo BLI, because the bioluminescence signals could be detected from the whole body of Bdnf-Luc Tg mice, we here examined the differences in the patterns of bioluminescence signals in Bdnf-Luc Tg mice when using D-luciferin, TokeOni, and seMpai, another D-luciferin analogue producing a near-infrared light. As recently reported, hepatic background signals were observed in wild-type mice when using TokeOni. We found the different patterns of the signals in Bdnf-Luc Tg mice when using different substrates. Notably, the bioluminescence signals were strongly observed around the liver when using D-luciferin and TokeOni. Corresponding to our previous observations, we detected the signals around the brain when using TokeOni. Compared to D-luciferin and TokeOni, the signals were widely detected from Bdnf-Luc Tg mice by seMpai. The signals produced by seMpai were likely strong around skeletal muscle in particular. Taken together, the patterns of bioluminescence signals in Bdnf-Luc Tg mice vary when using different luciferase substrates, and it is expected that the expression of Bdnf in the tissues and organs of interest could be visualized in living mice by selecting an appropriate substrate. Therefore, this method would be useful for evaluating the changes in Bdnf expression in physiological and pathophysiological conditions of living animals, probably contributing to further elucidation of the roles of BDNF in the peripheral tissues and organs, as well as in the brains. | | 2022年7月2日 11:00～12:00 沖縄コンベンションセンター 展示棟 ポスター会場1
3LBA-050
Large-scale functional connectomics of mouse visual cortex
*Marc M. Takeno(1), Daniel J. Bumbarger(1), Forrest Collman(1), Nuno da Costa(1), Sven Dorkenwald(2), Paul G. Fahey(3), Emmanouil Froudarakis(3), Kisuk Lee(2), Thomas Macrina(2), Stelios Papadopoulos(3), Xaq Pitkow(3), R. Clay Reid(1), Jacob Reimer(3), H. Sebastian Seung(2), Andreas S. Tolias(3), Nicholas L. Turner(2), Jingpeng Wu(2), Wenjing Yin(1), Szi-chieh Yu(2), MICrONS Consortium
1. Allen Institute for Brain Science, Seattle, WA, USA, 2. Princeton University, Princeton, NJ, USA, 3. Baylor College of Medicine, Houston, TX, USA
Keyword: ELECTRON MICROSCOPY, CALCIUM IMAGING, VISUAL CORTEX, CONNECTIVITY
We describe a functional connectomics dataset that combines physiology and ultrastructural anatomy in the same volume of mouse visual cortex. This dataset is the largest to date that combines functional calcium imaging and ultrastructural connectivity in the same cells. The responses of an estimated 75,000 neurons from primary visual cortex and three higher visual areas were recorded from, using calcium imaging, while the mouse viewed natural movies and parametric stimuli. Electron microscopy data of the same volume was automatically segmented, and more than 200,000 neuronal and non-neuronal cells were reconstructed, and 524 million synapses automatically identified, from the same tissue. Manual proofreading of some cells from this volume yielded complete dendritic arbors and local and inter-areal axonal projections. Of the 601 neurons that were proofread in the publicly available dataset, 78 excitatory neurons have axons and dendrites proofread to their maximal extension within the EM volume. Axon arbor length ranges from 2.5 to almost 19 mm, with a mean number of 714 synapses per axon (range: 192 – 1893). For 104 inhibitory neurons that were proofread for false merges, the number of output synapses ranged from 40 to 10,051. As an example, one completely proofread Layer 2/3 pyramidal cell has 3441 inputs and 1398 outputs identified, with 1239 synaptic partners. The dense reconstruction and scale of the dataset allow for analysis between groups of neurons (motifs), layer-layer connectivity, and functional and anatomical analysis of feedforward and feedback connections that are not possible with other modalities and methods. This dataset is released as an open access resource at www.microns-explorer.org with analysis tools for programmatic data access, and a web user interface to view morphologies and data. | | 2022年7月2日 11:00～12:00 沖縄コンベンションセンター 展示棟 ポスター会場1
3LBA-051
Automatic decoding package supported by forward variable selection for neuroimaging data optimizes
*Tung Dang(1,2), Alan S. R. Fermin(2), Maro G. Machizawa(2)
1. Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan, 2. Center for Brain, Mind, and KANSEI Sciences Research, Hiroshima University, Hiroshima, 734-8551 Japan
Keyword: Automatic machine learning, forward variable selection, fMRI, rumination
Background:
In the last few years, the applications of machine learning approaches have attracted an increasing interest for analyzing multiple modalities of Magnetic Resonance Imaging (MRI) databases. However, there are a number of major challenges. For example, the selections of the most appropriate machine learning algorithm for a specific fMRI data set have been still difficult for neuroscientists. Moreover, the high dimensionality of MRI datasets, that include thousands of voxels and hundreds of brain regions, significantly reduces the power of machine learning approaches for identifying a small group of brain regions that can make the most important contributions for classification and regression processes.
New method:
In this study, we developed a novel approach in order to overcome these challenges by combining two ideas: (i) We developed an automatic machine learning framework that can select automatically the best machine learning model for a input fMRI data set. (ii) We developed a parallel forward variable selection algorithm, which we named FVS, and coupled it with a machine learning algorithm that is selected at the previous step to maximize the predictive performance.
Results:
We systematically evaluated both classifier and regressor performances using our fMRI databases in decoding. As a result, our proposed FVS approach improves the accuracy of machine learning algorithm significantly with minimum increase of computational burden. Moreover, valid brain regions selection is essential for the analysis of high-dimensional fMRI data to predict the patients’ situation.
Conclusions:
The proposed approach presents the following advantages compared with the previous methods. Firstly, neuroscientists could benefit from the automatic selection of the most appropriate (or best performing) model for their own data sets. In our proposed approach, users only provide the input data sets and decide a type of machine learning algorithm that is classification or regression for their analysis. The automatic algorithm will rank a list of machine learning algorithms and recommend the best method for users’ data set. Next, the forward variable selection algorithm can identify a minimal-size core set of brain regions that can provide insights into the brain functions. | | 2022年7月2日 11:00～12:00 沖縄コンベンションセンター 展示棟 ポスター会場1
3LBA-052
Common Yoga protocol exerts psycho immune effects by activating angiogenic pathway: An open label single arm exploratory trial
*Dr. Akshay Anand(1), Kanupriya Sharma(1), Kalyan Maity(3), Sonu Goel(2)
1. Neuroscience Research Lab, Department of Neurology, Post Graduate Institute of Medical Education and Research, Chandigarh, INDIA, 2. Community Medicine and School of Public Health, Post Graduate Institute of Medical Education and Research, Chandigarh, INDIA, 3. Swami Vivekananda Yoga Anusandhana Samsthana, Bangalore, Karnataka, India
Keyword: Yoga, Angiogenesis, endothelial stem cells, Neurotrophic factor
Background: Sedentary lifestyle is a cause of various lifestyle disorders including atherosclerosis, diabetes, hypertension and cardiovascular diseases (CVDs). Lifestyle modification by inclusion of yoga in lifestyle have shown beneficial effects in disease prevention and psychological management but the molecular mechanism at the cellular level is not clearly unknown. Study participants: The current study was an open label single arm exploratory trial. Participants were invited to participate in Yoga based intervention. 19 female participants with mean age 40.82 ± 10.11 years were recruited for the study, 2 participants dropped out of the study. Intervention: 45 minutes of Common Yoga Protocol (CYP) intervention was given to the participants for 3 months (5 days/week). CYP is a standardized protocol approved by Govt. of India for International Yoga Day. It includes Asanas, Pranayama and meditation techniques. Methodology: Blood samples of the participants were taken at baseline, after 1 month and after 3 months of intervention. Blood samples were assessed for lipid profile, CD34+ cells, BDNF, VEGF and Angiogenin. Results: CD34+ cell count was found to be significantly increased after 3 months of CYP practice (from 18.18±7.32 cells/µl to 42.48±18.83 cells/µl) (p=0.001) followed by Angiogenesis markers which also showed an increasing trend. HDL levels also showed an increasing trend after CYP practice for 3 months (53.017±1.28 mg/dl to 63.94±5.66 mg/dl). Furthermore, HDL showed a significant positive correlation with VEGF and BDNF. Also, significant positive correlation was found between BDNF, VEGF and Angiogenin. Psychology and general health of the participants also showed a significant increment. Conclusion: CYP practice enhances the activation of angiogenesis pathways with increased expression of endothelial stem cell markers in peripheral blood. Hence, including CYP as an lifestyle intervention has the potential in prevention of CVDs. | | 2022年7月2日 11:00～12:00 沖縄コンベンションセンター 展示棟 ポスター会場1
3LBA-053
Cytoprotection properties of Tiger Milk Mushroom, Lignosus rhinocerotis on neuronal cell model
*YONG HUI TAN(1,3,2), Crystale Siew Ying Lim(2), Kah Hui Wong(3,4), Vikineswary Sabaratnam(1,3)
1. Institute of Biological Sciences, Faculty of Science, Universiti Malaya, 50603 Kuala Lumpur, Malaysia , 2. Department of Biotechnology, Faculty of Applied Sciences, UCSI University, UCSI Heights, Taman Connaught, 56000 Cheras, Kuala Lumpur, Malaysia, 3. Mushroom Research Centre, Institute of Biological Sciences, Faculty of Science, Universiti Malaya, 50603 Kuala Lumpur, Malaysia , 4. Department of Anatomy, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia
Keyword: Lignosus rhinocerotis, mitochondria membrane potential, pheochromocytoma cells, radical oxygen species
The neurite stimulatory effects of Lignosus rhinocerotis sclerotia extracts have long been well-documented. Nonetheless, there are limited studies on the cytoprotective effects of L. rhinocerotis extracts against hydrogen peroxide (H2O2)-induced oxidative stress, with only one previous study on L. rhinocerotis mycelium extracts, which found no cytoprotective properties. Thus far the cytoprotection potential of L. rhinocerotis sclerotia extracts is unknown. Hence, this study aims to investigate the cytoprotective capacity of L. rhinocerotis sclerotia extracts against H2O2-induced oxidative stress in PC12 cells as a neuronal cell model. L. rhinocerotis sclerotia extracts were prepared from aqueous and ethanolic extractions. In the L. rhinocerotis extract pre-treatment and co-treatment models of oxidative stress, cells induced with 30 μM of H2O2 were treated with L. rhinocerotis extracts for 24 hours, resulting in cytoprotection of up to 70.0±22.4% (pe-treatment with 320 μg/ml of aqueous extract) and 133.92±8.8% (co-treatment with 320 μg/ml of aqueous extract), respectively, compared to untreated H2O2-challenged cells. In order to investigate the mechanism of protection by the L. rhinocerotis extracts, the percentage of radical oxygen species (ROS) reduction and mitochondria membrane potential were measured using a Muse Cell Analyzer. Interestingly, treatment with L. rhinocerotis extracts did not significantly reduce cellular ROS levels (p > 0.05) in both pre-treatment and co-treatment models but instead resulted in a significant reduction (p < 0.05) in the percentage of depolarized cells observed (up to 37.6±0.6% in the pre-treatment model and up to 53.4±4.5% in the co-treatment model), compared to untreated H2O2-challenged cells. Estimation of apoptosis using ApoTox-Glo Triplex assays showed a significant reduction (p < 0.01) in caspase 3/7 activity in L. rhinocerotis extract co-treated groups. In conclusion, L. rhinocerotis sclerotia extract co-treatment of cells with H2O2-induced oxidative stress is more effective at PC12 cytoprotection. This could be attributed to the antioxidant capacity of the L. rhinocerotis sclerotia, which is well-reported in other studies. This study demonstrated that L. rhinocerotis extracts may play an essential role in PC12 cell maintenance and survival by preventing mitochondrial death and apoptotic cells in an H2O2-induced oxidative stress model. | | 2022年7月2日 11:00～12:00 沖縄コンベンションセンター 展示棟 ポスター会場1
3LBA-054
胸髄損傷ラットにおけるリハビリテーション訓練の効果－強制歩行と自発運動が行動回復と細胞の再編成にどのような影響を及ぼすか－
Effects of rehabilitative training on locomotor recovery and cellular reorganization in a rat spinal cord contusion model - comparison between forced and spontaneous running -
*塚越 千尋(1)、兼清 健志(2,3)、中野 法彦(2,3)、安部 征哉(2,4)、林部 美紀(2,5)、井出 千束(2,4)
1. 藍野大学医療保健学部作業療法学科、2. 藍野大学中央研究施設、3. びわこリハビリテーション大学リハビリテーション学部理学療法学科、4. びわこリハビリテーション大学リハビリテーション学部作業療法学科、5. 大阪保健医療大学保健医療学部作業療法学科
*Chihiro Tsukagoshi(1), Kenji Kanekiyo(2,3), Norihiko Nakano(2,3), Seiya Abe(2,4), Miki Hayashibe(2,5), Chizuka Ide(2,4)
1. Dept Occup Ther, Fac Health Sci, Aino Univ, Osaka, Japan, 2. Cent Biomed Lab, Aino Univ, Osaka, Japan, 3. Dept Phis Ther, Fac Rehab, Biwako Prof Univ of Rehab, Shiga, Japan, 4. Dept Occup Ther, Fac Rehab, Biwako Prof Univ of Rehab, Shiga, Japan, 5. Dept Occup Ther, Fac Rehab, Osaka Health Science Univ, Osaka, Japan
Keyword: rehabilitation, spinal cord injury, rat, spinal cord regeneration treatment
We have reported that the cell transplantation, such as bone marrow stromal cells, bone marrow-derived mononuclear cells, and choroid plexus epithelial cells, was effective for spinal cord injury. However, the recovery of animal behavior peaked in 2 to 3 weeks with these treatments alone, we believe that rehabilitation is important for further recovery of motor function after 4 weeks. In previous studies, it has been reported that exercise therapy for spinal cord injury model animals suppressed spasticity and pain, and that combined use of neural stem cell transplantation and treadmill training in chronic spinal cord injury model animals significantly restored motor function. Rehabilitation is considered to be a prevailing clinical approach to augment functional recovery, but its scientific basis for rehabilitation to enhance functional recovery, the type, timing, frequency, and intensity of exercise have not been completely elucidated. Here, we provided a model rat with moderate thoracic spinal cord injury to treadmill walking or spontaneous movement in a rich environment and investigated the rehabilitation effect by comparing with the control group. After the thoracic spinal cord injury model was created, it was divided into three different intervention groups after a rest period of 2 weeks (➀Treadmill group: 5 minutes for 2 to 4 weeks after surgery and 15 minutes for 5 to 8 weeks, ②Theme park group: 5 minutes treadmill walking 2-4 weeks after surgery, 15 minutes spontaneous exercise in a rich environment for 5-8 weeks, ③Control group: No rehabilitative training). Basso-Beattie-Bresnahan scores; (BBB) scores were followed up 2-8 weeks postoperatively to assess locomotion recovery. As a result, it was found that the behavior of both exercise groups recovered better than that of the control group, and that rehabilitative training was effective for behavior recovery. Furthermore, by analyzing the tissues, the effects of rehabilitative training on the degree of regenerative nerve extension and the distribution of glial cells are being investigated. Now we are searching for rehabilitative training that enhances the effect of spinal cord regeneration treatment and intend to further verify its effect. | | 2022年7月2日 11:00～12:00 沖縄コンベンションセンター 展示棟 ポスター会場1
3LBA-055
Disruption of retinal layers by laser photocoagulation affects Visuospatial memory and visual functions.
*Priya Mehra(1), Parul Bali(3), Jagtar Singh(1), Pradip Kumar Saha(4), Akshay Anand(2)
1. Department of Biotechnology, Panjab University, Chandigarh, India, 2. Neuroscience Research Lab, Department of Neurology, Postgraduate Institute of Medical Education and Research, Chandigarh, India, 3. Department of Biological Science, IISER - Indian Institute of Science Education and Research, Mohali, India, 4. Department of Obstetrics and Gynecology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
Keyword: Retinal degeneration, visual impairment, cognition, memory
Background- Visual pathway involves neuronal activity between presynaptic and post synaptic pathway to generate action potential to amplify the signal resulting in visual image formation. Although, various studies have been carried out to reverse the injury but these have not clinically translated successfully.
Methods- This study was conducted to evaluate the effect of injury on visual spatial memory by establishing a laser injury model and performing neurobehavioral tests (Morris Water Maze and Passive Avoidance). C57BL/6J male mice were used for the study. The laser spots with defined parameters were given to the mice retina around the optic disc using laser photocoagulation that disrupted the RPE layer of the retina. Fundus Fluorescein Angiography confirmed the establishment of animal model. Subsequently, visual-spatial memory was analysed by neurobehavioral tests and short-term memory by using Morris Water Maze (MWM) and Passive Avoidance.
Results- In neurobehavioral experiments, we found that escape latency time in both healthy and eight laser groups was comparable. In the passive avoidance test, the latency time was non-significant between the healthy and laser groups. This shows that visuospatial memory may not get affected by retinal injury induced by laser photocoagulation.
Conclusion- It may depend upon the intensity of the laser and the duration of the laser for which additional experiments are required.
Ethical Statement- Study was conducted after taking ethical approval from Institute Animal Ethical committee. The ethical approval number is 105/IAEC/720. | | 2022年7月2日 11:00～12:00 沖縄コンベンションセンター 展示棟 ポスター会場1
3LBA-056
Single nucleotide polymorphisms in Extracellular matrix genes ARMS2 (rs-10490924), COL8A1(rs-13081855), and COL10A1 (rs-1064583) confer risk for AMD in the North Indian population.
*priya battu(1), Shweta modgil(2), Suresh Sharma(3), kaushal Sharma(4), Ramandeep Singh(5), Akshay Anand(1)
1. Neuroscience research Lab, Department of Neurology, PGIMER, Chandigarh, 2. Emory University, GA, Atlanta, USA, 3. Department of statistics, Panjab university, Chandigarh, 4. Advanced Paediatric centre, PGIMER, Chandigarh, 5. Advanced Eye Centre, PGIMER, Chandigarh
Keyword: neuroretina, Extracellular matrix, Age Related macular degeneration, Single nucleotide polymorphisms
Background: Age-related macular degeneration (AMD) is a sight debilitating disease involving progressive degeneration of RPE and neuroretina. The global prevalence of AMD is increasing at an alarming rate. It is a complex multifactorial disease involving genetic, environmental, and sociodemographic components. GWAS has identified polymorphisms in genes involved in many pathways including the extracellular matrix pathway being implicated in AMD. But the role of these genes remains elusive.
Methods: The present study was carried out on 314 individuals (238 AMD patients and 76 controls) enrolled in Advanced eye centre, PGIMER, Chandigarh. ELISA was used for the estimation of proteins in the serum of the participants. Taqman genotyping assay was used for SNP genotyping of the samples.
Results: We found that the genotypic frequency of ARMS2, COL8A1, and COL10A1 is significantly different between cases and controls(p=.0001). Also, the protein levels of ARMS2, COL8A1, and COL10A1 were also significantly different in AMD and controls. We also performed statistical modeling to generate a logistic regression model for predicting AMD risk. We found that our model was able to predict the AMD risk with 86% accuracy.
Conclusion: We conclude that the SNPs in ECM genes are implicated in AMD in the Indian population and AMD risk can be predicted accurately on the basis of lifestyle factors, protein levels, and genotypic frequencies of studied ECM genes. | | 2022年7月2日 11:00～12:00 沖縄コンベンションセンター 展示棟 ポスター会場1
3LBA-057
Optical Neuroimage Studio (OptiNiSt):GUIベースで拡張性、汎用性をもつ、光学神経データ解析ツール
Optical Neuroimage Studio (OptiNiSt): GUI-based, extensible, scalable framework for neural image data analysis.
*山根 ゆか子(1)、Li Yuzhe(1)、Gutierrez Carlos Enrique(1,3)、秋山 祥伍(2)、佐伯 修也(2)、桑原 優(2)、蓮井 樹生(2)、金井 良太(2)、銅谷 賢治(1)
1. 沖縄科学技術大学院大学、2. 株式会社アラヤ、3. ソフトバンク株式会社
*Yukako Yamane(1), Yuzhe Li(1), Carlos Enrique Gutierrez(1,3), Shogo Akiyama(2), Shuya Saeki(2), Masaru Kuwabara(2), Shigeki Hasui(2), Ryota Kanai(2), Kenji Doya(1)
1. Okinawa Institute of Science and Technology Graduate University, 2. Araya Inc., 3. SoftBank Corp.
Keyword: Calcium imaging, 2-photon imaging, visualization, analysis tool
As neural calcium imaging is becoming a standard tool in neuroscience, vast volumes of optical imaging data are being collected. The number of data processing software tools is also increasing. Researchers who wish to apply new methods to their dataset need to prepare the environment for new analysis tools and sometimes reshape their data to fit each tool. Analysis pipelines can be complex and challenging to maintain their reproducibility. Here we developed Optical Neuroimage Studio (OptiNiSt) that helps researchers quickly try multiple data analysis methods, interactively visualize the results, and construct data analysis pipelines for reproducible analysis and efficient processing on HPC clusters. OptiNiSt is composed of a Web browser-based frontend and python-based backend. The analysis pipeline is created by selecting tools and connecting them by a graphic user interface, and the result of the analysis of each step is visualized. The analysis workflow and their environment are managed by snakemake (Mölder et al., F1000Research 2021). Currently, it includes Suite2P (Pachitariu et al., BioArxiv 2017) and CaImAn ( Giovannucci et al., eLife 2019) as standard ROI detection algorithms. It also includes several pre-installed analysis tools (neural population analysis, dimensionality reduction, finding subpopulations, neural decoding, etc.). Users can also add their own analysis tools as Python modules. The results are saved in .nwb (Neurodata Without Borders) standard format.The source code is made available from GitHub (https://github.com/oist/optinist). Users can install OptiNiSt to Linux, Mac, and Windows machines by Python “pip install” command or by downloading a virtual machine from DockerHub. OptiNiSt allows users to test multiple analysis methods with different parameters without writing codes or setting up computing environments. The workflow pipeline can be saved coherently with the analysis results for better reproducibility. OptiNiSt aims to make advanced analysis methods accessible to a wide range of researchers and to promote standardization of analysis protocols, as tools like SPM and MRtrix have served in the MRI community. | | 2022年7月2日 11:00～12:00 沖縄コンベンションセンター 展示棟 ポスター会場1
3LBA-058
Effect of controlled breathing intervention in COVID-19
*Manjari Rain(1), Akshay Anand(1,2,3), Goverdhan Dutt Puri(4), Pramod Avti(5), Vipin Kaushal(6)
1. Neuroscience Research Lab, Department of Neurology, Post Graduate Institute of Medical Education and Research, Chandigarh India, 2. CCYRN-Collaborative Center for Mind Body Intervention through Yoga, Post Graduate Institute of Medical Education and Research, Chandigarh, India, 3. Centre of Phenomenology and Cognitive Sciences, Panjab University, Chandigarh, India, 4. Department of Anaesthesia, Post Graduate Institute of Medical Education and Research, Chandigarh, India, 5. Department of Biophysics, Post Graduate Institute of Medical Education and Research, Chandigarh, India, 6. Department of Hospital Administration, Post Graduate Institute of Medical Education and Research, Chandigarh, India
Keyword: Covid 19, Yoga
Background- Yoga and meditation reduce risk of infectious and non-infectious diseases associated with respiratory distress. Yogic breathing also facilitates ventilation and reduces breathlessness. However, the effect of Yogic breathing on COVID-patients during and after the infection remains unclear. Method- COVID-positive practiced a 5-min routine and COVID-recovered and health care workers (HCWs) practiced 5-min and 15-min routines for 15 days. Among 18 biomarkers, the breathing intervention maintained WBC count and improved D-dimer, a predictor of COVID-19 severity, in such subjects (p<0.01). We also report lower D-dimer levels in susceptible HCWs practicing Yoga (p<0.01). Distance covered in 6-min walk test increased after intervention in COVID-positive (p=0.01) and HCW (p<0.01). Result- We have shown that stamina and exercise capacity improved in COVID-patients, recovered subjects and HCWs after the intervention. None of the nine neuropsychological scales showed significant difference. Yogic breathing is capable of improving health in mild and moderate cases of COVID-19. Intervention lowered D-dimer, thus reducing thrombosis, venous thromboembolism and vaccine-induced thrombotic thrombocytopenia in vaccinated individuals. Thus, lowering of D-dimer is also beneficial in high-altitude induced venous thromboembolism. Yogic breathing may be considered before and during high-altitude travel as high-altitude exposure leads to hypercoagulable state. Conclusion- Yogic breathing may also be practiced as a precautionary measure. We suggest that Yogic breathing may be considered as an integrative approach for management of COVID-patients and is also beneficial for HCWs and in high-altitude associated diseases. | | 2022年7月2日 11:00～12:00 沖縄コンベンションセンター 展示棟 ポスター会場1
3LBA-059
集団飼育および個別飼育をおこなったマウスの寒冷下行動性および自律性体温調節に与える影響の検証
Differences in behavioral and autonomic thermoregulatory responses to cold between group- and individual reared mice
*永島 計(1)、唐木 幸音(1)、増田 雄太(1)、加藤 一聖(1)、杉 泰佑(1)
1. 早稲田大学
*Kei Nagashima(1), Yukine Karaki(1), Yuta Masuda(1), Issei Kato(1), Taisuke Sugi(1)
1. Waseda University
Keyword: Huddling, brown fat, behavior ssytem, cold escape
Mice show huddling behavior in a cage, which is considered as both social and thermoregulatory behavior. The aim of the present study was to estimate such huddling behavior affect behavioral and autonomic responses when the mice were individually exposed to heat and cold. Methods. C57BL6/J male mice (n=47, 8 w old) were divided to two groups that were reared in individual and group (Group I and Group G, individually). In addition, they were reared at an ambient temperature (Ta) of 27°C or 22°C. First, their deep body temperature (Tb) and huddling behavior (only G group) were assessed. Second, cold-escape/warm-seeking behavior in both groups was evaluated with a behavior system in which mice were placed on cold plates but could find a warmer plate. Third, mice were exposed to 18˚C cold and Tb and the expression of UCP1 mRNA in the interscapular brown fat was evaluated. Results. The huddling behavior in the daytime was not different between Ta of 27°C and 22°C; however, that in the nighttime was greater at Ta of 22°C than that at 27°C. The heat-escape/cold-seeking behavior was decreased in Group G reared at Ta of 22°C than Group I reared at Ta of 27°C and 22°C and Group G reared at Ta of 27°C. The expression of UCP1 mRNA in the brown fat was grater in Group I reared at Ta of 22°C. Discussion Huddling behavior in the nighttime (i.e., active phase) increased in a cooler environment, suggesting an involvement of the behavior in thermoregulation. However, in the mice reared in group and cold, other cold-escape/warm-seeking behavior may be suppressed. In addition, heat production in cold that ws activated in the brown fat may also be suppressed in the mice. | | 2022年7月2日 11:00～12:00 沖縄コンベンションセンター 展示棟 ポスター会場1
3LBA-060
Inter-Brain Correlation during Communication in a Coordinating Task: an hyperscanning fMRI study
*Yi-Cing Chang(1), Ming-Hung Weng(2), Chun-Chia Kung(1), Der-Yow Chen(1)
1. Dept Psychol, National Chen Kung University, Tainan, Taiwan, 2. Dept Economic, National Chen Kung University, Tainan, Taiwan
Keyword: social cognition, social interaction, Hyperscanning, fMRI
Coordination is a critical process during interpersonal interaction, which require people to make corresponding decisions based on the behavior of others. However, due to the limitation of single-person neuroimaging paradigm, those studies are not able to explore the correlation between brain activity of the individuals during highly interactive social behaviors. In this study, we conducted a hyperscanning fMRI experiment to investigate the inter-brain correlation using a communicating coordination task. In each trial of the task, the reward distribution of two subjects were determined by their joint decision. They have to coordinate their choice so that only one of the dyad gets the higher reward, otherwise neither of them get the reward. Subjects expressed their intention in the declaration stage at the beginning of each trial. According to this communication, subjects made their final choice to form a joint decision to determine their reward distribution in the second stage. Subjects interact with an actual participant in half of trials, and interacting with computers in the others. Our results revealed that the brain regions related to theory of mind, cognitive control, and reward process were highly activated when interacting with actual people in contrast to computer. In addition, the activation of the right temporoparietal junction (rTPJ) and the right superior temporal sulcus (rSTS) were significantly related to the probability of successful coordination. Correlation analysis for the time series of two subjects’ brain activities suggested that there were inter-brain synchronizations between rTPJ, anterior insula (AI) and other related brain areas during interpersonal coordination. Although people performed a variety of behavior patterns in this coordination task, it also showed that the process of reasoning others’ mind and emotion were both strongly involved in the interpersonal coordination but not in human-computer coordination. Overall, this study revealed the neural mechanisms related to interpersonal coordination behaviors between the interacting dyad, and showed significant inter-brain synchronization. | | 2022年7月2日 11:00～12:00 沖縄コンベンションセンター 展示棟 ポスター会場1
3LBA-061
温度馴化に関与する新規遺伝子の探索と飼育温度に応じた温度受容ニューロンの感度調節
Screen for novel genes involved in temperature acclimation and sensitivity control of thermosensory neuron dependent on cultivating temperature
*村上 沙奈(1)、岡畑 美咲(1)、太田 茜(1)、久原 篤(1,2)
1. 甲南大学、2. PRIME,AMED
*Sana Murakami(1), Misaki Okahata(1), Akane Ohta(1), Atsushi Kuhara(1,2)
1. Konan University, 2. PRIME,AMED
Keyword: sensory neuron, temperature tolerance, ion channel , calcium imaging
Animals have the ability to respond appropriately to their environment. The nematode C. elegans changes its tolerance to cold temperatures depending on the past cultivation temperature. After the cultivation temperature changes, C. elegans acclimates to the new temperature within three hours, which is called temperature acclimation. The thermosensory neurons involved in temperature acclimation, as well as the thermoreceptors and channel molecules required to control the activity of these neurons, have been identified (Takagaki et al., EMBO rep., 2020; Okahata et al., Science Advances, 2019). A potassium channel KQT-3 expressed in thermosensory neurons is involved in temperature acclimation. We previously suggested that two knockout alleles of the kqt-3 mutations, aw1 and aw4, causes abnormally higher cold tolerance after cultivation at 25 degree followed to 15 degree for 3hr (25℃→15℃(3hr)→2℃: higher cold tolerance)(Okahata et al., 2019). However, we recently found that a different knockout allele of kqt-3 mutants, tm542, causes abnormally “lower” cold tolerance after cultivation at same condition. Besides, this abnormality of tm542 mutant was not rescued by introducing the wild-type kqt-3cDNA, speculating that a background mutation(s) excluding kqt-3(tm542) is caused by abnormally decreased cold tolerance. We then determined the genome sequence of kqt-3(tm542) by NGS, and found 11 second mutations causing loss of gene function. Cold acclimation of the mutants of these 11 genes were examined, and the abnormally decreased-cold tolerance similar to tm542 mutant was observed in a mutant impairing acetylcholine-dependent ion channels (ACR). We are investigating whether this ACR is actually involved in cold acclimation by phenotypic analysis of another KO allele. If ACR is involved in temperature acclimation, it will identify novel molecular pathway that regulates temperature acclimation.
Intracellular Ca2+ imaging revealed that at least three pairs of thermoreceptor neurons (ASJ, ADL and ASG) involved in cold tolerance and temperature acclimation. Previously reported, ASJ thermosensory activity changes depending on the worm cultivation temperature (Ohta et al., 2014). Recent study suggests that the maximum thermal response of ASJ as Ca2+ concentration changes was dependent on the cultivation temperature in a cell-autonomous manner (Motomura et al., under review). Although ADL thermosensory neuron were also found to increase their temperature responsiveness after cultivation at higher temperatures, it is not understood whether ASG memorizes cultivation temperature. We are therefore measuring whether the presence or absence of temperature memory for ASG and ADL neurons, after cultivation at various temperatures. We would also like to identify genes involved in temperature memory based on single cell transcriptome analysis of these thermosensory neuron. | | 2022年7月2日 11:00～12:00 沖縄コンベンションセンター 展示棟 ポスター会場1
3LBA-062
線虫の低温耐性に関わる新規のGPCR型温度受容体候補
A new candidate of GPCR-type thermoreceptor involved in cold tolerance of C. elegans
*森本 千夏(1)、宮崎 智瑛(1)、大西 康平(1)、三浦 徹(1)、太田 茜(1)、久原 篤(1,2)
1. 甲南大学、2. PRIME, AMED
*Chinatsu Morimoto(1), Chie Miyazaki(1), Kohei Ohnishi(1), Tohru Miura(1), Akane Ohta(1), Atsushi Kuhara(1,2)
1. Konan University, 2. PRIME, AMED
Keyword: C. elegans, cold tolerance, GPCR-type thermoreceptor
Thermosensation is essential for animal survival. To identify novel mechanisms of animal thermosensation, we are analyzing cold tolerance of nematode C. elegans, as a simple model. Although temperature signaling via trimeric G proteins have been found in C.elegans (Ohta et al., Nature commun, 2014; Kuhara et al., Science, 2008), GPCR-type thermoreceptors that could function upstream of the G proteins have not been found. To identify GPCR-type thermoreceptors regulating cold tolerance, we knocked down GPCR genes by exhaustive RNAi screening, resulting in 86 candidate genes involved in cold tolerance. Among them, we analyzed srx gene, whose knockout mutant showed abnormalities in cold tolerance. Using a whole neuron multicolor map strain called NeuroPAL, we found that SRX was expressed in a pair of olfactory neurons AWA located at the head, and found that srx mutant exhibited reduced-attraction behavior to AWA-sensed odorants, which was rescued by expressing wild-type srx gene in AWA of srx mutant. Namely, SRX functions in AWA olfactory neurons. To determine whether AWA neurons are responsive to temperature stimuli, we introduced calcium imaging of a pair of AWA neurons (AWA-left and AWA-right) during temperature stimuli, by using calcium indicator G-CaMP6f. The calcium concentration in AWA-left was decreased upon warming, whereas in AWA-right, spike-like calcium concentration increase was observed upon warming. These results suggest that AWA neurons respond to temperature and that temperature responsiveness is opposite between left and right AWA neurons. The left and right AWA neurons in srx mutant were less responsive to temperature stimuli, suggesting that GPCR SRX may be involved in the temperature response of AWA neurons. We interestingly found that ectopic expression of GPCR SRX in non-warm sensitive gustatory neuron ASER resulted in the acquisition of warm sensitivity. Together with these results suggest that GPCR SRX maybe sufficient to confer warm sensitivity for regulating cold tolerance. To verify whether SRX is actually a thermoreceptor, we are attempting to introduce reconstructive analysis with culture cell. | |
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