Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Department of Forensic Medicine, Hebei Medical University, Shijiazhuang 050017, China.
Int J Mol Sci. 2019 Jan 10;20(2):250. doi: 10.3390/ijms20020250.
The ventral tegmental area (VTA), a critical portion of the mesencephalic dopamine system, is thought to be involved in the development and maintenance of addiction. It has been proposed that the dopaminergic regulatory factors TH, Nurr1, and Pitx3 are crucial for determining the survival and maintenance of dopaminergic neurons. Thus, the present study investigated whether abnormalities in these dopaminergic regulatory factors in the VTA were associated with neuronal injury induced by chronic morphine dependence. Rat models with different durations of morphine dependence were established. Thionine staining was used to observe morphological changes in the VTA neurons. Immunohistochemistry and western blot were used to observe changes in the expression of the dopaminergic regulatory proteins TH, Nurr1, and Pitx3. Thionine staining revealed that prolonged morphine dependence resulted in dopaminergic neurons with edema, a lack of Nissl bodies, and pyknosis. Immunohistochemistry showed that the number of TH⁺, Nurr1⁺, and Pitx3⁺ cells, and the number of TH⁺ cells expressing Nurr1 or Pitx3, significantly decreased in the VTA after a long period of morphine dependence. Western blot results were consistent with the immunohistochemistry findings. Chronic morphine exposure resulted in abnormalities in dopaminergic regulatory factors and pathological changes in dopaminergic neurons in the VTA. These results suggest that dysregulation of dopaminergic regulatory factors in the VTA are associated with neuronal injury induced by chronic morphine dependence.
腹侧被盖区（VTA）是中脑多巴胺系统的关键部分，被认为与成瘾的发展和维持有关。有研究提出，多巴胺能调节因子 TH、Nurr1 和 Pitx3 对于多巴胺能神经元的存活和维持至关重要。因此，本研究旨在探讨 VTA 中这些多巴胺能调节因子的异常是否与慢性吗啡依赖诱导的神经元损伤有关。建立了不同吗啡依赖持续时间的大鼠模型。硫堇染色观察 VTA 神经元的形态变化。免疫组织化学和 Western blot 观察多巴胺能调节蛋白 TH、Nurr1 和 Pitx3 的表达变化。硫堇染色显示，长期吗啡依赖导致多巴胺能神经元水肿、尼氏体缺失和固缩。免疫组织化学显示，长期吗啡依赖后 VTA 中 TH⁺、Nurr1⁺和 Pitx3⁺细胞数量以及表达 Nurr1 或 Pitx3 的 TH⁺细胞数量明显减少。Western blot 结果与免疫组织化学结果一致。慢性吗啡暴露导致 VTA 中多巴胺能调节因子异常和多巴胺能神经元病理改变。这些结果表明，VTA 中多巴胺能调节因子的失调与慢性吗啡依赖诱导的神经元损伤有关。
