海马锥体神经元mGluR5介导慢性应激性记忆缺陷

IF 5 1区 医学 Q1 NEUROSCIENCES
Hong-Cheng Lu, Zhuo-Jun Du, Hao Chen, Ting Guo, Shu-Cai Yang, Xin Li
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引用次数: 0

摘要

慢性应激可引起多种生理缺陷,包括情绪障碍、睡眠障碍和记忆缺陷。然而,慢性应激性记忆缺陷的神经机制和潜在的药物靶点尚不明确。目的探讨代谢型谷氨酸受体5 (mGluR5)在慢性应激性记忆缺陷中的作用及其调控机制,探讨应激性记忆缺陷的潜在治疗靶点。方法采用行为测试法评估慢性应激对记忆的影响。电生理记录检测慢性应激后的突触输入。采用RNA测序来观察应激或mGluR5敲低后海马的转录变化。富集分析确定慢性应激性记忆缺陷的下游效应。结果慢性约束应激(CRS)损害海马依赖记忆,电生理记录显示慢性应激损害突触输入。随后,我们观察到CRS后mGluR5水平下降,这是学习和记忆的重要分子。mGluR5敲低会导致记忆缺陷并损害突触输入。CDPPB对mGluR5活性的增强可以恢复慢性应激性记忆缺陷和修复受损的突触输入。此外,我们发现垂体腺苷酸环化酶激活肽(PACAP)在CRS和mGluR5敲低后下调。应用PACAP可恢复CRS后受损的抑制性突触输入。结论mGluR5介导慢性应激性记忆缺陷,为应激性记忆缺陷的治疗提供了新的思路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

mGluR5 in Pyramidal Neurons in the Hippocampus Mediates Chronic Stress-Induced Memory Deficits

mGluR5 in Pyramidal Neurons in the Hippocampus Mediates Chronic Stress-Induced Memory Deficits

Background

Chronic stress causes variable profiles of physiological deficits, including mood disorders, sleep disorders, and memory deficits. However, the neural mechanisms and potential drug targets of chronic stress-induced memory deficit remain elusive.

Aims

This study aimed to explore the function and regulatory mechanisms of metabotropic glutamate receptor 5 (mGluR5) in chronic stress-induced memory deficit and investigate the potential therapeutic target for stress-related memory deficit.

Methods

Behavioral tests were used to assess the effects of chronic stress on memory. Electrophysiological recordings were conducted to examine the synaptic inputs after chronic stress. RNA sequencing was employed to achieve transcriptional alterations in the hippocampus after stress or mGluR5 knockdown. Enrichment analysis was performed to identify the downstream effector of chronic stress-induced memory deficits.

Results

Chronic restraint stress (CRS) impairs hippocampal-dependent memory and electrophysiological recordings reveal that chronic stress impairs synaptic inputs. Subsequently, we observe that the mGluR5 level declines after CRS, which is an important molecule for learning and memory. mGluR5 knockdown induces memory deficits and impairs synaptic inputs. Enhancement of mGluR5 activity by CDPPB could restore chronic stress-induced memory deficits and rescue impaired synaptic inputs. Furthermore, we identify that pituitary adenylyl cyclase activating peptide (PACAP) is down-regulated after CRS and mGluR5 knockdown. PACAP application could restore the impaired inhibitory synaptic inputs after CRS.

Conclusions

These results illuminate that the mGluR5 mediates chronic stress-induced memory deficits, which may provide promising strategies for treating stress-related memory deficits.

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来源期刊
CNS Neuroscience & Therapeutics
CNS Neuroscience & Therapeutics 医学-神经科学
CiteScore
7.30
自引率
12.70%
发文量
240
审稿时长
2 months
期刊介绍: CNS Neuroscience & Therapeutics provides a medium for rapid publication of original clinical, experimental, and translational research papers, timely reviews and reports of novel findings of therapeutic relevance to the central nervous system, as well as papers related to clinical pharmacology, drug development and novel methodologies for drug evaluation. The journal focuses on neurological and psychiatric diseases such as stroke, Parkinson’s disease, Alzheimer’s disease, depression, schizophrenia, epilepsy, and drug abuse.
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