The effect of different durations of morphine exposure on mesencephalic dopaminergic neurons in morphine dependent rats
The effect of different durations of morphine exposure on mesencephalic dopaminergic neurons in morphine dependent rats
复制标题
不同吗啡暴露时间对吗啡依赖大鼠中脑多巴胺能神经元的影响
DOI：
10.1016/j.neuro.2015.09.005
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发表时间：
2015-12-01
期刊：
影响因子：
3.4
通讯作者：
Li, Yingmin
中科院分区：
文献类型：
--
作者：
Shi, Weibo;Ma, Chunling;Li, Yingmin
中脑多巴胺能神经元与药物依赖的发展密切相关。甲状腺氨酸羟化酶（Thyrosine hydroxylase， TH）是多巴胺合成的限速酶，在多巴胺能神经元的存活中起着重要作用。因此，本研究考察了腹侧被盖区（VTA）和黑质（SN）多巴胺能神经元TH的变化，以及吗啡依赖不同持续时间对多巴胺能神经元的影响。建立吗啡依赖大鼠模型，采用石蜡包埋切片、免疫组织化学和western blotting观察TH蛋白表达变化。采用Fluoro-Jade B染色检测变性坏死，采用末端脱氧核苷酸转移酶介导的dUTP镍端标记（TUNEL）检测中脑多巴胺能神经细胞凋亡。免疫组化和western blotting结果显示，长期吗啡依赖大鼠VTA和SN内TH阳性细胞数量和蛋白水平均显著降低。长时间吗啡暴露后，VTA和SN内多巴胺能神经细胞变性坏死，未见凋亡细胞。VTA和SN多巴胺能神经细胞数量随着吗啡依赖时间的延长而减少，这很可能是由于吗啡毒性导致神经细胞变性和坏死所致。(C) 2015爱思唯尔公司版权所有。
Mesencephalic dopaminergic neurons are heavily involved in the development of drug dependence. Thyrosine hydroxylase (TH), the rate-limiting enzyme in dopamine synthesis, plays an important role in the survival of dopaminergic neurons. Therefore, this study investigated TH changes in dopaminergic neurons of the ventral tegmental area (VTA) and substantia nigra (SN), as well as the morphine effects on dopaminergic neurons induced by different durations of morphine dependence. Models of morphine dependence were established in rats, and paraffin-embedded sections, immunohistochemistry and western blotting were used to observe the changes in the expression of TH protein. Fluoro-Jade B staining was used to detect degeneration and necrosis, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling (TUNEL) detected the apoptosis of mesencephalic dopaminergic nerve cells. Immunohistochemistry and western blotting showed that the number of TH positive cells and the protein levels in the VTA and SN were significantly decreased in the rats with a long period of morphine dependency. With prolonged morphine exposure, the dopaminergic nerve cells in the VTA and SN showed degeneration and necrosis, while apoptotic cells were not observed. The number of VTA and SN dopaminergic nerve cells decreased with increasing periods of morphine dependence, which was most likely attributable to the degeneration and necrosis of nerve cells induced by morphine toxicity. (C) 2015 Elsevier Inc. All rights reserved.