Department of Biochemistry, Kanazawa Medical University School of Medicine, 1-1 Daigaku, Uchinada, Kahoku-gun, Ishikawa 920-0293, Japan.
Department of Physiology, Kanazawa Medical University School of Medicine, 1-1 Daigaku, Uchinada, Kahoku-gun, Ishikawa 920-0293, Japan.
Int J Mol Sci. 2023 Feb 13;24(4):3736. doi: 10.3390/ijms24043736.
Chronic stress can affect gene expression in the hippocampus, which alters neural and cerebrovascular functions, thereby contributing to the development of mental disorders such as depression. Although several differentially expressed genes in the depressed brain have been reported, gene expression changes in the stressed brain remain underexplored. Therefore, this study examines hippocampal gene expression in two mouse models of depression induced by forced swim stress (FSS) and repeated social defeat stress (R-SDS). Transthyretin (Ttr) was commonly upregulated in the hippocampus of both mouse models, as determined by microarray, RT-qPCR, and Western blot analyses. Evaluation of the effects of overexpressed Ttr in the hippocampus using adeno-associated virus-mediated gene transfer revealed that TTR overexpression induced depression-like behavior and upregulation of Lcn2 and several proinflammatory genes (Icam1 and Vcam1) in the hippocampus. Upregulation of these inflammation-related genes was confirmed in the hippocampus obtained from mice vulnerable to R-SDS. These results suggest that chronic stress upregulates Ttr expression in the hippocampus and that Ttr upregulation may be involved in the induction of depression-like behavior.
慢性应激会影响海马体中的基因表达，改变神经和脑血管功能，从而导致抑郁症等精神障碍的发展。虽然已经报道了抑郁大脑中几个差异表达的基因，但应激大脑中的基因表达变化仍未得到充分探索。因此，本研究通过强迫游泳应激（FSS）和重复社交挫败应激（R-SDS）两种抑郁小鼠模型，检测了海马体中的基因表达。微阵列、RT-qPCR 和 Western blot 分析表明，转甲状腺素蛋白（Ttr）在两种小鼠模型的海马体中均普遍上调。使用腺相关病毒介导的基因转移评估海马体中过表达 Ttr 的效果表明，TTR 过表达会导致类似抑郁的行为，并上调海马体中的 Lcn2 和几种促炎基因（Icam1 和 Vcam1）。在易患 R-SDS 的小鼠的海马体中证实了这些与炎症相关的基因的上调。这些结果表明，慢性应激会在上调海马体中的 Ttr 表达，而 Ttr 的上调可能参与诱导类似抑郁的行为。
