College of Forensic Medicine, Hebei Medical University, Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Hebei Province, Shijiazhuang 050017, China.
School of Forensic Medicine, Xinxiang Medical University, Xinxiang 453003, China.
Anal Cell Pathol (Amst). 2021 Sep 8;2021:7852710. doi: 10.1155/2021/7852710. eCollection 2021.
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.
由于社会和心理压力，越来越多的人处于压力状态，这可能导致精神障碍。先前的研究表明，中脑多巴胺能神经元不仅与奖励相关行为有关，还与应激引起的精神障碍有关。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。免疫组织化学结合基于显微镜的多色组织细胞术（MMTC）用于研究多巴胺能神经元数量的变化。双免疫荧光标记用于研究内质网应激（ERS）蛋白 GRP78 和 CHOP 在多巴胺能神经元中的表达变化。我们的结果表明，长期应激导致 VTA 中多巴胺能神经元的病理改变，如多巴胺能神经元的尼氏体缺失和固缩。MMTC 的免疫组织化学表明，慢性应激暴露导致多巴胺能神经元显著减少。双免疫荧光标记显示内质网应激蛋白参与了多巴胺能神经元的损伤。总之，这些结果表明内质网应激参与了应激暴露引起的中脑多巴胺能神经元损伤。
