7月26日（金）15:30～15:50 第10会場（万代島ビル 6F 会議室）
2WD10ca1-2
前障の興奮性神経細胞はカテコラミンの放出を介して不安様行動を制御する
Misaki Niu（丹生 光咲）1，Atsushi Kasai（笠井 淳司）1，Hisato Igarashi（五十嵐 久人）1，Wataru Tanabe（田邊 航）1，Takahiro Kuwaki（桑木 崇宏）1，Masato Tanuma（田沼 将人）1，Kaoru Seiriki（勢力 薫）1,2，Yukio Ago（吾郷 由希夫）3，Takanobu Nakazawa（中澤 敬信）1,4，Akihiro Yamanaka（山中 章弘）5，Hitoshi Hashimoto（橋本 均）1,6,7,8
1大阪大院薬神経薬理
2大阪大・国際共創大学院学位プログラム推進機構
3大阪大院薬薬剤
4大阪大歯薬理
5名古屋大環境医神経系２
6大阪大院連合小児発達子どものこころ
7大阪大データビリティフロンティア機構
8大阪大先導的学際研究機構
Acute psychological stress induces negative emotional states including anxiety and behavioral responses which are associated with neurotransmitters and neuromodulators release. However, the neuronal mechanisms underlying stress responses remain largely unknown. Recently we used brain-wide activity mapping and machine learning and observed the neuronal activation in the claustrum prominently differs between the mice which were received psychological stress and controls. To examine whether stress-responsive neurons in the claustrum mediate stress-induced anxiety-like behavior and change the neuronal activities of the other brain regions, here we coinjected an adeno-associated virus vector for pharmacogenetics and a tamoxifen-induced Cre-loxP recombination system. Pharmacogenetic activation of stress-responsive glutamatergic neurons in the anterior part of the claustrum significantly increased the anxiety-like behavior in the open field test and elevated plus maze test. In addition, the activation resulted in neuronal activations of several nuclei including the basolateral amygdala. We also examined the extracellular levels of dopamine and noradrenaline in the medial prefrontal cortex using microdialysis techniques and found that activation of the claustral glutamatergic neurons results in increased release of dopamine and noradrenaline. Finally, pharmacological inhibition of dopamine D2 or beta-adrenergic receptors attenuated the claustral activation-induced anxiety-like behaviors. These results suggest that glutamatergic neurons in the anterior claustrum mediate stress-induced anxiety-like behaviors through modulating the neural activities of the limbic system and the release of catecholamine in the prefrontal cortex. | | 7月26日（金）15:50～16:10 第10会場（万代島ビル 6F 会議室）
2WD10ca1-3
IDO1は社会的敗北ストレス下におけるストレス脆弱性を制御する
Kazuo Kunisawa（國澤 和生）1,2，Akihiro Mouri（毛利 彰宏）2,4，Aika Kosuge（小菅 愛加）2，Tsubasa Iida（飯田 翼）2，Bolati Wulaer（Wulaer Bolati）1,3，Yasuko Yamamoto（山本 康子）3，Kuniaki Saito（齋藤 邦明）3,4，Toshitaka Nabeshima（鍋島 俊隆）1,4
1藤田医科大院保健先進診断システム
2藤田医科大院保健レギュラトリーサイエンス
3藤田医科大院保健病態制御解析学
4特定非営利活動法人医薬品適正使用推進機構
Indoleamine 2,3-dioxygenase 1 (IDO1) metabolizes the essential amino acid tryptophan into kynurenine (KYN), which is involved in neural activity via the KYN pathway. It has been proposed that IDO1 implicates in the pathogenesis of major depressive disorder (MDD). However, the underlying mechanisms remain poorly understood. In the present study, we investigated an involvement of KYN synthesis in chronic social defeat stress, a mouse model of depression. In the chronic social defeat stress, C57BL/J mice were exposed to aggressor ICR mouse for 10 consecutive days. Chronic stress persistently reduced the duration of time spent at the interaction zone in the social interaction test 4 weeks after the last stress exposure. We found reduced expression of IDO1 and KYN concentration in the prefrontal cortex of mice 4 weeks, but not 1 day after the last stress exposure. Double immunostaining showed the IDO1 immunoreactivity was mainly observed in neurons of the prefrontal cortex of control mice, and which was reduced in the mice exposed to chronic stress. To explore whether IDO1-mediated KYN reduction in mice exposed to the stress is involved in persistent social impairments, KYN (50 mg/kg; i.p.) was administrated to the stressed mice from 1 day after the last stress exposure for 4 weeks. KYN attenuated the impairment of social behaviors. Furthermore, injection of adeno-associated virus (AAV) expressing shRNA against IDO1 into the prefrontal cortex increased susceptibility to persistent social impairments induced by a subthreshold social defeat stress for 3 days. These results suggest that IDO1 may be a critical regulator of stress vulnerability and KYN could be a potential target for the development of antidepressants. |
