کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4338761 1614883 2011 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Heat shock protein 70 kDa over-expression and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced nigrostriatal degeneration in mice
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
Heat shock protein 70 kDa over-expression and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced nigrostriatal degeneration in mice
چکیده انگلیسی

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, striatal 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.

▶Hsp70 over-expression fails to suppress MPTP-induced neuronal death in mice substantia nigra. ▶HSP70 is unable to prevent MPTP-induced nigrostriatal axon terminal degeneration. ▶HSP70 does not improve nigrostriatal axon terminal recovery subsequent to MPTP treatment. ▶In conclusion, HSP70 alone is not sufficient to protect against neurotoxic parkinsonism in mice.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience - Volume 193, 13 October 2011, Pages 323–329
نویسندگان
, , , ,