期刊
JOURNAL OF NEUROCHEMISTRY
卷 77, 期 4, 页码 1181-1184出版社
BLACKWELL SCIENCE LTD
DOI: 10.1046/j.1471-4159.2001.00366.x
关键词
MPTP; Parkinson's disease; alpha SYN; transgenic mice; tyrosine hydroxylase
Environmental and genetic factors that contribute to the pathogenesis of Parkinson's disease are discussed. Mutations in the alpha -synuclein (alpha SYN) gene are associated with rare cases of autosomal-dominant Parkinson's disease. We have analysed the dopaminergic system in transgenic mouse lines that expressed mutant [A30P]alpha SYN under the control of a neurone-specific Thy-1 or a tyrosine hydroxylase (TH) promoter. The latter mice showed somal and neuritic accumulation of transgenic [A30P]alpha SYN in TH-positive neurones in the substantia nigra. However, there was no difference in the number of TH-positive neurones in the substantia nigra and the concentrations of catecholamines in the striatum between these transgenic mice and non-transgenic littermates. To investigate whether forced expression of [A30P]alpha SYN increased the sensitivity to putative environmental factors we subjected transgenic mice to a chronic 1-methyl-4-phenyl-1,2,3.6-tetrahydropyridine (MPTP) regimen. The MPTP-induced decrease in the number of TH-positive neurones in the substantia nigra and the concentrations of catecholamines in the striatum did not differ in any of the [A30P]alpha SYN transgenic mouse lines compared with wild-type controls. These results suggest that mutations and forced expression of alpha SYN are not likely to increase the susceptibility to environmental toxins in vivo.
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