Department of Brain Sciences, Daegu Gyeongbuk Institute of Science and Technology (DGIST), 333 Techno Jungang Daero, Hyeonpung-Myeon, Dalseong-Gun, Daegu, 42988, Republic of Korea.
Mol Brain. 2024 Jun 3;17(1):31. doi: 10.1186/s13041-024-01105-6.
Chronic psychological stress is a critical factor for neurological complications like anxiety disorders, dementia, and depression. Our previous results show that chronic restraint stress causes cognitive deficits and mood dysregulation by inducing autophagic death of adult hippocampal neural stem cells (NSCs). However, it is unknown whether other models of psychological stress also induce autophagic death of adult hippocampal NSCs. Here, we show that chronic unpredictable stress (CUS) for 10 days impaired memory function and increased anxiety in mice. Immunohistochemical staining with SOX2 and KI67 revealed a significant reduction in the number of NSCs in the hippocampus following exposure to CUS. However, these deficits were prevented by NSC-specific, inducible conditional deletion of Atg7. These findings suggest that autophagic death of adult hippocampal NSCs is a critical pathogenic mechanism underlying stress-induced brain disorders.
慢性心理应激是焦虑障碍、痴呆和抑郁等神经并发症的一个关键因素。我们之前的研究结果表明，慢性束缚应激通过诱导成年海马神经干细胞（NSCs）自噬性死亡导致认知缺陷和情绪失调。然而，其他类型的心理应激是否也会诱导成年海马 NSCs 的自噬性死亡尚不清楚。在这里，我们证明慢性不可预测应激（CUS）持续 10 天会损害小鼠的记忆功能并增加其焦虑。免疫组织化学染色显示，SOX2 和 KI67 的表达，在经历 CUS 后，海马中的 NSCs 数量显著减少。然而，通过 NSCs 特异性、诱导型条件性 Atg7 缺失可以预防这些缺陷。这些发现表明，成年海马 NSCs 的自噬性死亡是应激诱导的脑疾病的一个关键发病机制。
