Leibniz Institute for Resilience Research, 55122 Mainz, Germany.
Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University Mainz, 55128 Mainz, Germany.
Cells. 2022 Oct 27;11(21):3405. doi: 10.3390/cells11213405.
Upon chronic stress, a fraction of individuals shows stress resilience, which can prevent long-term mental dysfunction. The underlying molecular mechanisms are complex and have not yet been fully understood. In this study, we performed a data-driven behavioural stratification together with single-cell transcriptomics of the hippocampus in a mouse model of chronic social defeat stress. Our work revealed that in a sub-group exhibiting molecular responses upon chronic stress, the dorsal hippocampus is particularly involved in neuroimmune responses, angiogenesis, myelination, and neurogenesis, thereby enabling brain restoration and homeostasis after chronic stress. Based on these molecular insights, we applied rapamycin after the stress as a proof-of-concept pharmacological intervention and were able to substantially increase stress resilience. Our findings serve as a data resource and can open new avenues for further understanding of molecular processes underlying stress response and for targeted interventions supporting resilience.
在慢性应激下，一部分个体表现出应激弹性，这可以预防长期的精神功能障碍。其潜在的分子机制很复杂，尚未完全被理解。在这项研究中，我们通过慢性社交挫败应激的小鼠模型，进行了数据驱动的行为分层以及海马体的单细胞转录组学研究。我们的工作揭示了在慢性应激下表现出分子反应的亚组中，背侧海马体特别参与神经免疫反应、血管生成、髓鞘形成和神经发生，从而在慢性应激后实现大脑的修复和稳态。基于这些分子见解，我们在应激后应用雷帕霉素作为概念验证的药物干预，并能够显著提高应激弹性。我们的发现提供了一个数据资源，并为进一步理解应激反应的分子过程以及支持弹性的靶向干预提供了新的途径。
