HEAT SHOCK PROTEIN 70 KDA OVER-EXPRESSION AND 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE-INDUCED NIGROSTRIATAL DEGENERATION IN MICE

被引:3
|
作者
Gao, L. [1 ,2 ]
Diaz-Martin, J. [1 ,2 ]
Dillmann, W. H. [3 ]
Lopez-Barneo, J. [1 ,2 ]
机构
[1] Univ Seville, Hosp Univ Virgen Rocio, Inst Biomed Sevilla IBiS, ICSIC, Seville 41013, Spain
[2] CIBERNED, Zamudio, Spain
[3] Univ Calif San Diego, Dept Med, Div Endocrinol & Metab, San Diego, CA 92103 USA
关键词
heat shock protein 70 kDa; MPTP; Parkinson's disease; transgenic mice; ENDOPLASMIC-RETICULUM STRESS; ALPHA-SYNUCLEIN AGGREGATION; PARKINSONS-DISEASE; SUBSTANTIA-NIGRA; MOUSE MODEL; DOPAMINERGIC-NEURONS; GENE-EXPRESSION; C-JUN; MPTP; PROTECTS;
D O I
10.1016/j.neuroscience.2011.07.028
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Oxidative damage in the dopaminergic neurons of substantia nigra pars compacta (SNpc) plays an important role in the pathogenesis of Parkinson's disease (PD). Heat shock proteins 70 kDa (HSP70s) are a sub-family of molecular chaperones involved in not only protein folding and degradation but also antioxidant defense and anti-apoptotic pathways. Here, a transgenic mice over-expressing an inducible form of Hsp70 was used to determine whether HSP70 affects 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced nigrostriatal degeneration, an experimental model of PD. The Hsp70 transgenic animals exhibited a high level of expression of HSP70 protein in ventral mesencephalon. Dopaminergic cell death in the SNpc was similar between wild-type and Hsp70 transgenic mice with either acute (40 mg/kg, single dose) or chronic (20 mg/kg, three times/week during 1 month) MPTP treatment. In addition, striatel dopamine loss was not different between wild-type and transgenic animals. Three months after the acute MPTP treatment, dopamine loss was partially recovered into a similar level between wild-type and transgenic groups. In conclusion, over-expression of Hsp70 does not suppress dopaminergic neuronal damage at either the somata or the axon terminals of dopaminergic neurons. Hsp70 over-expression does not help axon terminal regeneration either. These results indicate that HSP70 alone is not sufficient to reduce MPTP-induced dopaminergic neuronal damage. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:323 / 329
页数:7
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