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严重束缚应激诱导海马突触细胞凋亡及小胶质细胞吞噬作用的初步分析

Preliminary analysis of hippocampus synaptic apoptosis and microglial phagocytosis induced by severe restraint stress.

机构信息

Self Defense Force, Fukuoka Hospital, Fukuoka, Japan.

Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

出版信息

Neuropsychopharmacol Rep. 2023 Mar;43(1):120-125. doi: 10.1002/npr2.12298. Epub 2022 Nov 23.

Abstract

AIM

Several studies reported stress-induced microglial phagocytosis, but the biochemical mechanisms by which stress alters microglial synaptic phagocytosis are not fully uncovered. Local or limited apoptosis without cell death was observed at neuronal synapses in previous studies, and proposed as an upstream mechanism for microglial synapse elimination. In this micro-report, we aimed to preliminary examine local synaptic apoptosis in the mouse hippocampus following severe restraint stress, and its effect on microglial phagocytosis.

METHODS

Mice were exposed to 10-day water immersion restraint stress (WIRS). Brain sections including stratum lucidum in the hippocampal CA3 subfield were stained with antibodies against cleaved caspase 3, ionized calcium-binding adapter molecule1 (Iba1), lysosomal-associated membrane protein1 (LAMP1), vesicular glutamate transporter1 (VGLUT1). Co-localization among these proteins were calculated.

RESULTS

Our image analysis revealed that synaptic apoptosis was increased while there were no significant changes in microglial phagocytic activity and synaptic phagocytosis following 10-day WIRS.

CONCLUSION

Severe restraint stress enhanced pre-synaptic apoptosis in mouse CA3 stratum lucidum region, but did not promote microglial phagocytosis. The phenomenon microglia fail to phagocytose weakened and unnecessary synapses may be related to pathology of stress.

摘要

目的

有几项研究报告称,应激会引发小胶质细胞吞噬作用,但应激改变小胶质细胞突触吞噬作用的生化机制尚未完全阐明。在之前的研究中,在神经元突触观察到局部或有限的凋亡而没有细胞死亡,并提出作为小胶质细胞突触消除的上游机制。在这个微型报告中,我们旨在初步研究严重束缚应激后小鼠海马体中的局部突触凋亡及其对小胶质细胞吞噬作用的影响。

方法

将小鼠暴露于 10 天的浸水束缚应激(WIRS)中。用针对半胱天冬酶 3 、钙结合接头蛋白 1(Iba1)、溶酶体相关膜蛋白 1(LAMP1)、囊泡谷氨酸转运体 1(VGLUT1)的抗体对包括海马 CA3 亚区的齿状回在内的脑切片进行染色。计算这些蛋白质之间的共定位。

结果

我们的图像分析显示,在 10 天 WIRS 后,突触凋亡增加,而小胶质细胞吞噬活性和突触吞噬作用没有显著变化。

结论

严重的束缚应激增强了小鼠 CA3 齿状回区的前突触凋亡,但并没有促进小胶质细胞的吞噬作用。小胶质细胞不能吞噬作用减弱和不必要的突触的现象可能与应激的病理学有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eef7/10009418/5b1bef15fcb1/NPR2-43-120-g001.jpg

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