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

1. Io Horikawa, …, Tomoyuki Furuyashiki. Chronic stress alters lipid mediator profiles associated with immune-related gene expressions and cell compositions in mouse bone marrow and spleen. J Pharmacol Sci 154, 279-293 (2024).
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).
5. Tomoyuki Furuyashiki, Shiho Kitaoka. Neural mechanisms underlying adaptive and maladaptive consequences of stress: Roles of dopaminergic and inflammatory responses. Psychiatry Clin Neurosci 73, 669-675 (2019).
6. Xiang Nie, …, Tomoyuki Furuyashiki. The innate immune receptors TLR2/4 mediate repeated social defeat stress-induced social avoidance through prefrontal microglial activation. Neuron 99, 464-479 (2018).
7. Ryota Shinohara, …, Tomoyuki Furuyashiki. Dopamine D1 receptor subtype mediates acute stress-induced dendritic growth in excitatory neurons of the medial prefrontal cortex and contributes to suppression of stress susceptibility in mice. Mol Psychiatry 23, 1717-1730 (2018).
8. Yuichi Deguchi, …, Tomoyuki Furuyashiki, Shuh Narumiya. mDia and ROCK mediate actin-dependent presynaptic remodeling regulating synaptic efficacy and anxiety. Cell Rep 17, 2405-2417 (2016).
9. Kohei Tanaka, Tomoyuki Furuyashiki, …, Shuh Narumiya. Prostaglandin E₂-mediated attenuation of mesocortical dopaminergic pathway is critical for susceptibility to repeated social defeat stress in mice. J Neurosci 32, 4319-4329 (2012).
10. Tomoyuki Furuyashiki, Shuh Narumiya. Stress responses: the contribution of prostaglandin E₂ and its receptors. Nat Rev Endocrinol 7, 163-175 (2011).

 

 

担当分野：　薬学生化学　杉本（4357)