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Sensitivity to MPTP is not increased in Parkinson's disease‐associated mutant α‐synuclein transgenic mice
Author(s) -
RathkeHartlieb Silvia,
Kahle Philipp J.,
Neumann Manuela,
Ozmen Laurence,
Haid Sibylle,
Okochi Masayasu,
Haass Christian,
Schulz Jörg B.
Publication year - 2001
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2001.00366.x
Subject(s) - substantia nigra , mptp , tyrosine hydroxylase , genetically modified mouse , striatum , transgene , dopaminergic , parkinson's disease , biology , pars compacta , alpha synuclein , endocrinology , medicine , dopamine , mutant , microbiology and biotechnology , genetics , gene , disease
Environmental and genetic factors that contribute to the pathogenesis of Parkinson's disease are discussed. Mutations in the α‐ synuclein (α 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]αSYN 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]αSYN 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]αSYN 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 ]α SYN transgenic mouse lines compared with wild‐type controls. These results suggest that mutations and forced expression of αSYN are not likely to increase the susceptibility to environmental toxins in vivo .