Sensitivity to MPTP is not increased in Parkinson' s disease-associated mutant α-synuclein transgenic mice

Abstract

Environmental and genetic factors that contribute to the pathogenesis of Parkinson's disease are discussed. Mutations in the α-synuclein (αSYN) 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-phenyl1,2,3,6-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 [A3OP]αSYN 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.