一般口演
精神疾患・発達障害 |
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| 7月6日（木） 16:30-17:30 Room D
1O⑦-1
内側前頭前野におけるIGF-1はケタミンの抗うつ作用に重要である
Release of IGF-1 in the medial prefrontal cortex is essential for the antidepressant effects caused by ketamine
近藤 誠1, 出山 諭司2, 島田 昌一3, 金田 勝幸2
1. 大阪公立大学大学院医学研究科 脳神経機能形態学, 2. 金沢大学医薬保健研究域薬学系 薬理学, 3. 大阪大学大学院医学系研究科 神経細胞生物学
Makoto Kondo1, Satoshi Deyama2, Shoichi Shimada3, Katsuyuki Kaneda2
1. Dept of Anat & Neurosci, Grad Sch of Med, Osaka Metropolitan Univ, Osaka, Japan, 2. Dept of Mol Pharmacol, Institute of Med, Pharma & Health Sci, Kanazawa Univ, Kanazawa, Japan, 3. Dept of Neurosci & Cell Biol, Grad Sch of Med, Osaka University, Suita, Japan
Ketamine produces rapid and sustained antidepressant actions. Previous papers demonstrated that the release of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor in the medial prefrontal cortex (mPFC) is essential for the antidepressant effects caused by ketamine. However, the role of other neurotrophic factors in the antidepressant effects of ketamine has not been fully studied. In this study, we investigated the role of insulin-like growth factor 1 (IGF-1) in the mPFC in the antidepressant actions of ketamine. In vivo microdialysis showed that ketamine significantly increased extracellular IGF-1 levels in the mPFC of mice. Infusion of an IGF-1 neutralizing antibody (nAb) into the mPFC before or after ketamine injection blocked the antidepressant effects of ketamine. In addition, antidepressant effects induced by the intra-mPFC infusion of BDNF and IGF-1 were not inhibited by co-infused IGF-1 nAb and BDNF nAb, respectively. Furthermore, intra-mPFC infusion of IGF-1 nAb after ketamine injection blocked the antidepressant effects of ketamine in lipopolysaccharide (LPS)-induced depression model mice. These results suggest that persistent IGF-1 release in the mPFC is essential for the antidepressant effects of ketamine, independently of BDNF. | | 7月6日（木） 16:30-17:30 Room D
1O⑦-2
空間トランスクリプトームで解明する統合失調症における分子変化
Unraveling the molecular signatures of schizophrenia with spatial transcriptomics
吉永 怜史1,2, レオン フリオ3, 日野 瑞城4,5, 安藤 吉成3, ムーディー ジョナサン3, 長岡 敦子4, 北澤 彩子1,2, 林 周宏2, 仲嶋 一範2, ホン チュンチャウ3, 國井 泰人4,5, シン ジェイ3,6, 久保 健一郎1,2
1. 慈恵医大 解剖, 2. 慶應大 解剖, 3. 理研IMS, 4. 福島医大 神経精神, 5. 東北大 災害科学国際研 災害精神医学, 6. シンガポールゲノム研 ゲノム制御
Satoshi Yoshinaga1,2, Julio Leon3, Mizuki Hino4,5, Yoshinari Ando3, Jonathan Moody3, Atsuko Nagaoka4, Ayako Kitazawa1,2, Kanehiro Hayashi2, Kazunori Nakajima2, Chung Chau Hon3, Yasuto Kunii4,5, Jay Shin3,6, Ken-ichiro Kubo1,2
1. Dept. of Anat., Jikei Univ. Sch. Med., Tokyo, Japan, 2. Dept. of Anat., Keio Univ. Sch. Med., Tokyo, Japan, 3. IMS RIKEN, Kanagawa, Japan, 4. Dept. of Neuropsychiatry, Fukushima Medical Univ., Japan, 5. Dept. of Disaster Psychiatry, IRIDeS, Tohoku Univ., Sendai, Japan, 6. Lab. of Regulatory Genomics, Genome Inst. of Singapore, Singapore
Schizophrenia (SCZ) is a chronic, severe psychiatric disorder affecting ~1% of the population. The underlying causes and molecular signatures are largely unknown, because of our brains' highly heterogeneous and intricate cellular makeup. To tackle this, we took advantage of spatial transcriptomics, which can take molecular, cellular, and histological complexity into account, to elucidate the molecular pathological changes in SCZ. We used the anterior cingulate cortex of donated postmortem brains from Fukushima brain bank for psychiatric research. We utilized Visium spatial transcriptomics (4 SCZ brains vs. 4 controls) and GeoMx-DSP whole transcriptome analysis (3 SCZ vs. 3 controls) with single nucleus RNA sequencing (2 SCZ vs. 2 controls). This allowed us to conduct data integration, trans annotation, differential gene expression analysis, and recognize main tissue domains altered in SCZ. Results revealed alterations in astrocytic molecular signatures and ligand-receptor interactions in SCZ as well as morphological changes in a subpopulation of astrocytes according to immunohistochemistry. GeoMx-DSP WTA allowed us to elucidate clear neuronal cortical layer differences in control. However, lesser differences were observed in SCZ. Our findings suggest a pivotal role of astrocytes, neurons, and their altered microenvironment in the pathogenesis of SCZ. | | 7月6日（木） 16:30-17:30 Room D
1O⑦-3
The effect of traditional medicine maca in ASD model mice
傅 品悦1,2, Shuxin Luo4, Zhongyu Liu4, 古原 和美1, 辻 隆宏1,3, 東田 陽博1, 横山 茂1,2, Jing Zhong4,5, 辻 知陽1
1. 金沢大学子どものこころの発達研究センター, 2. 大阪大学大学院 連合小児発達学研究科, 3. 福井大学医学部眼科学教室, 4. 広西中医薬大学生理学教室 中国・南寧市, 5. 広西中医薬大学第一附属病院 中国・南寧市
Fu Pinyue1,2, Shuxin Luo4, Zhongyu Liu4, Kazumi Furuhara1, Takahiro Tsuji1,3, Haruhiro Higashida1, Shigeru Yokoyama1,2, Jing Zhong4,5, Chiharu Tsuji1
1. Research Center for Child Mental Development, Kanazawa University, 2. United Graduate School of Child Development, Osaka University, Kanazawa Campus, 3. Department of Ophthalmology, Faculty of Medical Sciences, University of Fukui, 4. Physiological Department, Guangxi University of Chinese Medicine, Nanning, China, 5. The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, China
Abstract
[Background] ASD is a congenital and lifelong neurodevelopmental disorder whose main symptoms are a lack of social communication, narrow interests, and stereotypical repetitive behaviors. There are no drugs available to treat social impairment in patients with ASD. In experimental animal models, maca (Lepidium meyenii) has been shown to have beneficial effects on memory and learning. Although maca is known as a fertility enhancer, it has been shown to have multiple functions.
[Method] We first prepared maca and established a mouse model of autism exposed to VPA in utero (VPA mice). Then we investigated the effects of maca on social function deficits through animal behavioral experiments and immunochemical tests.
[Result] Deficits in social interaction behaviors and impairments in social memory in mice with an autism model were alleviated by maca. Maca supplementation attenuated the deficits in social memory. c-Fos, a marker of neuronal activation. Expressed cells and c-Fos-positive oxytocin (OT) neurons were increased in the brain areas of maca supplementation. In maca-treated VPA mice, brain areas where OT cells were present were increased.
[Conclusion] This study shows for the first time that maca improves impaired social recognition memory in mice with an ASD model. The improvement in social memory may be achieved through the upregulation of the oxytocin pathway. | | 7月6日（木） 16:30-17:30 Room D
1O⑦-4
インドールアミン-2,3ジオキシゲナーゼ１を介した血液胎盤関門の破綻は母体免疫活性化による出生仔の神経発達障害に関与する
IDO1 is involved in the maternal immune activation-induced blood-placental barrier disruption and behavioral impairments
毛利 彰宏1,4, 山岸 周平1, 國澤 和生1, 新島 萌1, 倉橋 仁美1, 窪田 悠力1, 長谷川 眞也1, 齋藤 邦明2,4, 鍋島 俊隆3,4
1. 藤田医科大学大学院保健学研究科レギュラトリーサイエンス, 2. 藤田医科大学大学院保健学研究科先進診断システム開発分野, 3. 藤田医科大学大学院保健学研究科健康医科学創造共同研究部門, 4. 医薬品適正使用推進機構
Akihiro Mouri1,4, Shuhei Yamagishi1, Kazuo Kunisawa1, Moe Niijima1, Hitomi Kurahashi1, Hisayoshi Kubota1, Masaya Hasegawa1, Kuniaki Saito2,4, Toshitaka Nabeshima3,4
1. Department of Regulatory Science for Evaluation and Development of Pharmaceuticals and Devices, Fujita Health University Graduate School of Health Sciences, Aichi, Japan., 2. Department of Advanced Diagnostic System Development, Fujita Health University Graduate School of Health Sciences, Aichi, Japan., 3. Laboratory of Health and Medical Science Innovation, Fujita Health University Graduate School of Health Sciences, Aichi, Japan., 4. Japanese Drug Organization of Appropriate Use and Research, Aichi, Japan.
Maternal immune activation (MIA) by viral infection impairs fetal brain development. But, it is not fully explored how it invasive fetal brain via placenta. Tryptophan metabolizing enzyme indoleamine 2,3-dioxygenase1 (IDO1) is upregulated by immune activation. Here, we examined the effect of MIA on the blood-placental barrier (BPB) and the involvement of IDO1 in the MIA-induced BPB disruption and abnormal behavior of offspring. Maternal polyinosinic acid-polycytidylic acid (polyI:C) injection induced social withdrawal and object recognition memory impairment in offspring. Evans blue dye infiltrates more into the fetal brain and body from polyI:C-injected dams, suggesting increased the permeability of blood-placental barrier. Among the tight junction related proteins, polyI:C injection reduced the expression of claudin5 in the placenta. Maternal polyI:C injection increased tryptophan metabolites including kynurenine by induction of macrophage-derived IDO1 in placenta. IDO1 inhibitor and maternal IDO1 deficiency attenuated the decrease of claudin5 expression and infiltration of macrophages in the placenta and social withdrawal and object recognition memory impairment in the offspring of polyI:C-injected dams. These results suggest maternal polyI:C injection increased BPB permeability via induction of macrophage-derived IDO1 in placenta and induced abnormal behavior in offspring. | |
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