ストレス感受性におけるシナプス性ミトコンドリア制御の役割

• Published in: 日本薬理学会年会要旨集 p. 1-SS-13
• Main Authors: 山下, 朋美, 永井, 碧, 加藤, 太朗, 片岡, 洋祐, 清末, 優子, 永井, 裕崇, 古屋敷, 智之, 沼, 知里, 大野, 伸彦, 川島, 祐介
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2022
• Subjects: depression; mitochondria; neuron; stress
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.95.0_1-SS-13

Chronic social stress induces neuronal dysfunctions in the medial prefrontal cortex (mPFC) for emotional and cognitive disturbances. However, the subcellular mechanism remains elusive. Here we examined ultrastructural and multi-omics changes in the mPFC in a mouse model of social defeat stress. Acute stress induced dendritic membrane deformation with mitochondrial swelling in mPFC neurons, leading to dendritic atrophy after chronic stress. Synaptic, but not bulk tissue, proteomes in the mPFC differentiated naïve and stressed mice and further uncovered two distinct states in stressed mice. Proteins involved in mitochondrial metabolic functions mostly decreased with chronic stress regardless of the synaptic proteomic state. By contrast, proteins responsible for mitochondrial homeostasis increased in stressed mice with a specific synaptic proteomic state associated with behavioral resilience to chronic stress. These findings suggest that the balance between mitochondrial metabolic dysfunction and its maintenance at mPFC synapses determines stress susceptibility in mice.