Endoplasmic Reticulum Stress Is Associated with the Mesencephalic Dopaminergic Neuron Injury in Stressed Rats.

Shiba Niu,Shanyong Yi,Yingmin Li,Yang Li,Weibo Shi,Guanglong He,Bin Cong,Xia Liu

doi:10.1155/2021/7852710

Abstract

An increasing number of people are in a state of stress due to social and psychological pressures, which may result in mental disorders. Previous studies indicated that mesencephalic dopaminergic neurons are associated with not only reward-related behaviors but also with stress-induced mental disorders. To explore the effect of stress on dopaminergic neuron and potential mechanism, we established stressed rat models of different time durations and observed pathological changes in dopaminergic neurons of the ventral tegmental area (VTA) through HE and thionine staining. Immunohistochemistry coupled with microscopy-based multicolor tissue cytometry (MMTC) was employed to investigate the number changes of dopaminergic neurons. Double immunofluorescence labelling was used to investigate expression changes of endoplasmic reticulum stress (ERS) protein GRP78 and CHOP in dopaminergic neurons. Our results showed that prolonged stress led to pathological alteration in dopaminergic neurons of VTA, such as missing of Nissl bodies and pyknosis in dopaminergic neurons. Immunohistochemistry with MMTC indicated that chronic stress exposure resulted in a significant decrease in dopaminergic neurons. Double immunofluorescence labelling showed that the endoplasmic reticulum stress protein took part in the injury of dopaminergic neurons. Taken together, these results indicated the involvement of ERS in mesencephalic dopaminergic neuron injury induced by stress exposure.

Highlights

With the rapid development of modern society, more and more people are in a state of stress as a result of increasing social competition and psychological pressures, which has resulted in a number of undesirable mental disorders and remains a major medical and public health issue [1, 2]
Our results showed that prolonged stress led to pathological changes in dopaminergic neurons of ventral tegmental area (VTA), such as missing of Nissl bodies and pyknosis in dopaminergic neurons
The number of dopaminergic neurons labeled with the specific marker Tyrosine hydroxylase (TH) was detected, and our findings suggested that there was a significant decrease in dopaminergic neurons in VTA after long-term exposure to stress

Summary

Introduction

With the rapid development of modern society, more and more people are in a state of stress as a result of increasing social competition and psychological pressures, which has resulted in a number of undesirable mental disorders and remains a major medical and public health issue [1, 2]. Previous studies have indicated that chronic stress leads to elevation of hypothalamo-pituitary-adrenal axis activity [6], a decrease in hippocampal [7] and cortical [8, 9] pyramidal neurons, and altered activity of dopaminergic neurons in the VTA [10, 11]. The critical involvement of dopaminergic neurons of the VTA in the neural circuit modifications is responsible for various adaptive changes and pathological behaviors, which include mental disorders [12, 13]

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