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长期航天复合应激通过破坏海马突触可塑性诱导模型大鼠抑郁行为。

Long-term spaceflight composite stress induces depressive behaviors in model rats through disrupting hippocampus synaptic plasticity.

机构信息

School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, China.

School of Medicine and Health, Harbin Institute of Technology, Harbin, China.

出版信息

CNS Neurosci Ther. 2024 Mar;30(3):e14438. doi: 10.1111/cns.14438. Epub 2023 Oct 17.

DOI:10.1111/cns.14438
PMID:37849237
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10916436/
Abstract

INTRODUCTION

Long-term spaceflight composite stress (LSCS) can cause adverse effects on human systems, including the central nervous system, which could trigger anxiety and depression.

AIMS

This study aimed to identify changes in hippocampus synaptic plasticity under LSCS.

METHODS

The present study simulated the real long-term space station environment by conducting a 42-day experiment that involved simulating microgravity, isolation, noise, circadian rhythm disruptions, and low pressure. The mood and behavior of the rats were assessed by behavior test. Transmission electron microscopy and patch-clamp were used to detect the changes in synapse morphology and electrophysiology, and finally, the expression of NMDA receptor channel proteins was detected by western blotting.

RESULTS

The results showed that significant weight loss, anxiety, and depressive behaviors in rats were observed after being exposed to LSCS environment for 42 days. The synaptic structure was severely damaged, manifested as an obvious decrease in postsynaptic density thickness and synaptic interface curvature (p < 0.05; p < 0.05, respectively). Meanwhile, LTP was significantly impaired (p < 0.0001), and currents in the NMDAR channel were also significantly reduced (p < 0.0001). Further analysis found that LSCS decreased the expression of two key subtype proteins on this channel.

CONCLUSION

These results suggested that LSCS-induced depressive behaviors by impairing synaptic plasticity in rat hippocampus.

摘要

简介

长期太空飞行复合应激(LSCS)会对人体系统造成不良影响,包括中枢神经系统,这可能引发焦虑和抑郁。

目的

本研究旨在确定 LSCS 下海马突触可塑性的变化。

方法

本研究通过进行 42 天的实验模拟了真实的长期空间站环境,模拟微重力、隔离、噪声、昼夜节律紊乱和低压。通过行为测试评估大鼠的情绪和行为。使用透射电子显微镜和膜片钳技术检测突触形态和电生理学的变化,最后通过 Western blot 检测 NMDA 受体通道蛋白的表达。

结果

结果表明,大鼠在暴露于 LSCS 环境 42 天后体重明显减轻,出现焦虑和抑郁行为。突触结构严重受损,表现为突触后密度厚度和突触界面曲率明显减少(p<0.05;p<0.05,分别)。同时,LTP 明显受损(p<0.0001),NMDAR 通道电流也明显减少(p<0.0001)。进一步分析发现,LSCS 降低了该通道两个关键亚单位蛋白的表达。

结论

这些结果表明,LSCS 通过损害大鼠海马突触可塑性引起抑郁行为。

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