International Journal of Medical Sciences

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25 July 2017

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Int J Med Sci 2017; 14(4):340-347. doi:10.7150/ijms.18623

Research Paper

Recombinant AAV8-mediated intrastriatal gene delivery of CDNF protects rats against methamphetamine neurotoxicity

Lizheng Wang1, Zixuan Wang1, Xiaoyu Xu2, Rui Zhu1, Jinpeng Bi1, Wenmo Liu1, Xinyao Feng1, Hui Wu1, Haihong Zhang1, Jiaxin Wu1, Wei Kong1, 3, Bin Yu1✉, Xianghui Yu1, 3✉

1. National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China;
2. Evidence Identification Center, Department of Public Security of Jilin Province, Changchun 130051, China;
3. Key Laboratory for Molecular Enzymology and Engineering, the Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, China.

Abstract

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 in vitro and in vivo. In vitro, CDNF protein increased the survival rate and reduced the tyrosine hydroxylase (TH) loss of METH-treated PC12 cells. In vivo, 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.

Keywords: Methamphetamine, Neurotoxicity, Adeno-associated virus, CDNF, Neuroprotection, Dopamine.

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How to cite this article:
Wang L, Wang Z, Xu X, Zhu R, Bi J, Liu W, Feng X, Wu H, Zhang H, Wu J, Kong W, Yu B, Yu X. Recombinant AAV8-mediated intrastriatal gene delivery of CDNF protects rats against methamphetamine neurotoxicity. Int J Med Sci 2017; 14(4):340-347. doi:10.7150/ijms.18623. Available from http://www.medsci.org/v14p0340.htm