Wang Lizheng, Wang Zixuan, Xu Xiaoyu, Zhu Rui, Bi Jinpeng, Liu Wenmo, Feng Xinyao, Wu Hui, Zhang Haihong, Wu Jiaxin, Kong Wei, Yu Bin, Yu Xianghui
National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China.
Evidence Identification Center, Department of Public Security of Jilin Province, Changchun 130051, China.
Int J Med Sci. 2017 Mar 17;14(4):340-347. doi: 10.7150/ijms.18623. eCollection 2017.
Methamphetamine (METH) exerts significant neurotoxicity in experimental animals and humans when taken at high doses or abused chronically. Long-term abusers have decreased dopamine levels, and they are more likely to develop Parkinson's disease (PD). To date, few medications are available to treat the METH-induced damage of neurons. Glial cell line-derived neurotrophic factor (GDNF) has been previously shown to reduce the dopamine-depleting effects of neurotoxic doses of METH. However, the effect of cerebral dopamine neurotrophic factor (CDNF), which has been reported to be more specific and efficient than GDNF in protecting dopaminergic neurons against 6-OHDA toxicity, in attenuating METH neurotoxicity has not been determined. Thus, the present study aimed to evaluate the neuroprotective effect of CDNF against METH-induced damage to the dopaminergic system and . , CDNF protein increased the survival rate and reduced the tyrosine hydroxylase (TH) loss of METH-treated PC12 cells, METH was administered to rats following human CDNF overexpression mediated by the recombinant adeno-associated virus. Results demonstrated that CDNF overexpression in the brain could attenuate the METH-induced dopamine and TH loss in the striatum but could not lower METH-induced hyperthermia.
甲基苯丙胺（METH）在高剂量服用或长期滥用时，会对实验动物和人类产生显著的神经毒性。长期滥用者多巴胺水平降低，且更易患帕金森病（PD）。迄今为止，几乎没有药物可用于治疗METH诱导的神经元损伤。胶质细胞系源性神经营养因子（GDNF）先前已被证明可减轻神经毒性剂量的METH对多巴胺的消耗作用。然而，脑源性多巴胺神经营养因子（CDNF）在减轻METH神经毒性方面的作用尚未确定，据报道，CDNF在保护多巴胺能神经元免受6-羟基多巴胺（6-OHDA）毒性方面比GDNF更具特异性和有效性。因此，本研究旨在评估CDNF对METH诱导的多巴胺能系统损伤的神经保护作用。此外，CDNF蛋白提高了METH处理的PC12细胞的存活率，并减少了酪氨酸羟化酶（TH）的损失，在重组腺相关病毒介导的人CDNF过表达后，将METH注射给大鼠。结果表明，大脑中CDNF的过表达可减轻METH诱导的纹状体中多巴胺和TH的损失，但不能降低METH诱导的体温过高。
