最先端研究セミナー

講演者：　 古屋敷 智之（神戸大学医学研究科 教授）

演題：　Biological Mechanisms of Stress in Mental Illness

日時： 2024年7月31日（水）12：00- 13：00

Abstract:

Stress from adverse and demanding conditions affects cognitive and emotional functions and risks mental illness such as depression. Since the biological basis of stress has remained elusive, therapeutic development targeting stress has not been established. Rodent studies using stress models have elucidated multiple neurobiological consequences of stress, depending on the stress conditions. We have found that acute stress induces dendritic hypertrophy of prefrontal neurons via the dopamine D1 receptor, augmenting stress resilience, whereas chronic stress attenuates prefrontal dopaminergic activity and induces dendritic atrophy of prefrontal neurons through microglia-driven neuroinflammation, leading to behavioral disturbances. In addition, chronic stress mobilizes leukocytes from the bone marrow, synergizing with neuroinflammation to promote behavioral disturbances. These findings have been considered clinically relevant since clinical studies have reported the association between inflammation and depression. Despite the great advancement in understanding the biological basis of stress, various mysteries remain, such as how acute and chronic stress causes different neurobiological consequences, how the individual variability of stress susceptibility emerges, and how multi-organ interactions underlie stress-induced neuropsychiatric dysfunctions. In this talk, I will present our recent studies about biological mechanisms of stress pathology with rodent stress models and discuss their relevance to therapeutic developments for mental illness.

References

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2. Shiho Kitaoka, …, Tomoyuki Furuyashiki. Repeated social defeat stress induces HMGB1 nuclear export in prefrontal neurons, leading to social avoidance in mice. Cells 12, 1789 (2023).
3. Satoshi Akiyama, …, Tomoyuki Furuyashiki. Chronic social defeat stress increases the amounts of 12-lipoxygenase lipid metabolites in the nucleus accumbens of stress-resilient mice. Sci Rep 12, 11385 (2022).
4. Yuka Ishikawa, …, Tomoyuki Furuyashiki. Repeated social defeat stress induces neutrophil mobilization in mice: maintenance after cessation of stress and strain-dependent difference in response. Br J Pharmacol 178, 827-844 (2021).
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担当分野：　薬学生化学　杉本（4357)