一般口演

一般口演6

2021/9/30　18:00～19:00　オンデマンド D会場 O6-1 海馬アストロサイトに発現するprotein targeting to glycogenは、PACAPシグナルの下流でグルタミン酸受容体の発現調節を介して短期記憶を制御する Protein targeting to glycogen expressed in hippocampal astrocytes regulates short-term memory via modulation of glutamate receptor expression downstream of PACAP signaling ^○神戸悠輝, Nguyen Thi Thu, Takashi Kurihara, Atsuro Miyata 鹿児島大学大学院・医歯学総合研究科・生体情報薬理学 ^○Yuki Kambe, Nguyen Thi Thu, Takashi Kurihara, Atsuro Miyata Department of Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University We have previously reported that pituitary adenylate cyclase-activating polypeptide (PACAP) signaling in astrocytes contributes to neuroplasticity. On the other hand, lactate and other signaling molecules produced by glycogen metabolism in astrocytes are called glyotransmitters and have been recently reported to contribute to neuroplasticity. However, the function of protein targeting to glycogen (PTG), which is known to be a central regulator of glycogen metabolism, in learning and memory has not been clarified. We first used an adeno-associated virus expressing HA-tagged ribosomal protein l22 downstream of an astrocyte-specific promoter to selectively collect mRNA from hippocampal astrocytes. We found that PTG was highly expressed in astrocytes. When cultured astrocytes were exposed to PACAP, the expression of PTG was significantly increased. Furthermore, the expression of PTG was significantly increased in the hippocampus of mice after memory acquisition in the passive avoidance test. In order to analyze the function of PTG in the hippocampus, we designed short hairpin RNA (shRNA) that suppresses PTG expression in mouse hippocampal astrocytes and performed behavioral experiments. In the Y-maze test and the passive avoidance test, short-term memory performance was significantly decreased. Furthermore, we examined the expression of ionotropic glutamate receptor subunits in the hippocampus of mice in which PTG expression was suppressed, and found that the expression of GluR1, GluR2, and NR2A was significantly suppressed. These results suggest that astrocytic PTG may affect the expression of glutamate receptors in neurons and regulate short-term memory in the hippocampus. We are now investigating what factors are released from astrocytes and how they affect neurons.		2021/9/30　18:00～19:00　オンデマンド D会場 O6-2 側坐核ドーパミンD2受容体-中型有棘神経細胞(D2R-MSN)内のアセチルコリンシグナルによる忌避学習の亢進 Acetylcholine signaling in D2R-MSN neurons and its stimulation of aversive learning. ^○山橋幸恵¹, You-Shin Lin², Sho Iwanaga², Tomohiro Kawashima², Yuya Tokumoto², Yo Watanabe², Md. Omar Faruk², Xijian Zhang³, Daisuke Tsuboi¹, Naoaki Saito⁵, Taku Nagai³, Kiyofumi Yamada⁴, Kozo Kaibuchi¹ 1.藤田医科大学, 2.Cell Pharmacology, Nagoya University, 3.Division of Behavioral Neuropharmacology, Fujita Health University, 4.Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University, 5.Laboratory of Molecular Pharmacology, Kobe University ^○Yukie Yamahashi¹, You-Shin Lin², Sho Iwanaga², Tomohiro Kawashima², Yuya Tokumoto², Yo Watanabe², Md. Omar Faruk², Xijian Zhang³, Daisuke Tsuboi¹, Naoaki Saito⁵, Taku Nagai³, Kiyofumi Yamada⁴, Kozo Kaibuchi¹ 1.Research Project for Neural and Tumor Signaling, Fujita Health University, 2.Cell Pharmacology, Nagoya University, 3.Division of Behavioral Neuropharmacology, Fujita Health University, 4.Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University, 5.Laboratory of Molecular Pharmacology, Kobe University Acetylcholine is considered a critical neuromodulator for aversive learning in pharmacological settings. This molecule activates dopamine receptor D2-medium spiny neurons (D2R-MSNs) through muscarinic receptor M1 (M1R). However, acetylcholine intracellular signaling beyond the M1R-PKC cascade in D2R-MSNs that stimulates aversive learning remains unelucidated. Our phosphoproteomics analysis revealed 116 PKC substrate candidates, including the Rac activator β-PIX. Acetylcholine activated p21-activated kinase (PAK), a drug target candidate for CNS disorders, through the M1R-PKC-β-PIX cascade ex vivo. The cholinesterase inhibitor donepezil and aversive stimuli activated the M1R-PKC-PAK cascade in D2R-MSNs in vivo. PAK regulated D2R-MSN-mediated aversive learning, indicating the involvement of the M1R-PKC-PAK cascade in aversive learning. Finally, donepezil enhanced aversive learning through PAK in D2R-MSNs. These findings demonstrated enhanced D2R-MSN-mediated aversive learning by acetylcholine. Our discovery of the intracellular mechanism of donepezil indicates a potential strategy for treating CNS disorders with aversive learning deficits, including Alzheimer’s disease and schizophrenia.

2021/9/30　18:00～19:00　オンデマンド D会場 O6-3 相互に接続された脳オルガノイドの複雑な神経活動と光刺激による短期記憶誘導 Complex Activity and Short-term Memories in Reciprocally Connected Cerebral Organoids ^○大崎達哉, Yoshiho Ikeuchi Institute of Industrial Science ^○Tatsuya Osaki, Yoshiho Ikeuchi Institute of Industrial Science Macroscopic axonal connections in the human brain distribute information and neuronal activity across the brain. Although this complexity previously hindered elucidation of functional connectivity mechanisms, brain organoid technologies have recently provided novel avenues to investigate human brain function by constructing small segments of the brain in vitro. Here, we describe the neural activity of reciprocally connected human cerebral organoids cultured on a multi-electrode array. Compared to conventional organoids, connected organoids produced significantly more intense and complex oscillatory activity. Optogenetic manipulations revealed that the connected organoids maintained temporal patterns of external stimuli, indicating that the connected organoids were able to retain temporal memory. Our findings suggest that connected organoids provide a useful approach to understand the roles of macroscopic circuits in the human brain.		2021/9/30　18:00～19:00　オンデマンド D会場 O6-4 ジオスゲニン高濃度含有ヤマイモエキスによる健常人の認知機能向上：ランダム化二重盲検プラセボ対照クロスオーバー試験による検討 Diosgenin-rich yam extract enhances cognitive function: a placebo-controlled, randomized, double-blind, crossover study of healthy adults ^○東田千尋, Yuna Inada, Ximeng Yang 富山大学和漢医薬学総合研究所神経機能学領域 ^○Chihiro Tohda, Yuna Inada, Ximeng Yang Section of Neuromedical Science, Institute of Natural Medicine, University of Toyama In our previous study, Diosgenin, a yam-derived compound, facilitated the repair of axonal atrophy and synaptic degeneration and improved memory dysfunction in a transgenic mouse model of AD. Diosgenin also enhanced neuronal excitation and memory function even in normal mice. We hypothesized that diosgenin, either isolated or in an extract, may represent a new category of cognitive enhancers reinforcing morphologically and functionally neuronal networks. This study aimed to investigate the effects of a diosgenin-rich yam extract (DYE) on cognitive enhancement in healthy volunteers. This placebo-controlled, randomized, double-blind, crossover study was conducted with the approval of the Ethics Committee of the University of Toyama. Each subject signed an informed consent form prior to study entry. Twenty- eight healthy volunteers were recruited from Toyama Prefecture, and randomly assigned to receive either a yam extract or placebo. Animal experiments indicated that an oil solvent mediated the most efficient distribution of diosgenin into the blood and brain after oral administration, and was a critical factor in the cognitive benefits. Therefore, test samples (placebo and DYE) were prepared with olive oil. The intake period was 12 weeks, and a 6-week washout period separated the two crossover intake periods. The Japanese version of RBANS test was used for neurocognitive assessment, and adverse effects were monitored through blood testing. DYE consumption for 12 weeks yielded significant increases in total RBANS score. Among the 12 individual standard cognitive subtests, DYE use significantly improved semantic fluency. No adverse effects were detected. The DYE treatment appeared to safely enhance cognitive function in healthy adults.