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.

中文翻译：

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内质网应激与应激大鼠中脑多巴胺能神经元损伤有关


越来越多的人由于社会和心理压力而处于压力状态，从而可能导致精神障碍。先前的研究表明，中脑多巴胺能神经元不仅与奖励相关的行为有关，还与压力诱发的精神障碍有关。为了探讨应激对多巴胺能神经元的影响及其潜在机制，我们建立了不同持续时间的应激大鼠模型，并通过HE和硫堇染色观察腹侧被盖区（VTA）多巴胺能神经元的病理变化。采用免疫组织化学结合基于显微镜的多色组织细胞术（MMTC）来研究多巴胺能神经元的数量变化。采用免疫荧光双重标记研究多巴胺能神经元内质网应激（ERS）蛋白GRP78和CHOP的表达变化。我们的结果表明，长期应激会导致 VTA 多巴胺能神经元发生病理改变，例如尼氏体缺失和多巴胺能神经元固缩。 MMTC 免疫组织化学表明，慢性应激暴露导致多巴胺能神经元显着减少。免疫荧光双重标记显示内质网应激蛋白参与了多巴胺能神经元的损伤。综上所述，这些结果表明 ERS ​​参与了应激暴露引起的中脑多巴胺能神经元损伤。