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• W1693098624 abstract "Abstract Sigma-1 receptor ( σ 1 R) has been reported to be decreased in nigrostriatal motor system of Parkinson's disease patients. Using heterozygous and homozygous σ 1 R knockout ( σ 1 R +/− and σ 1 R −/− ) mice, we investigated the influence of σ 1 R deficiency on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-impaired nigrostriatal motor system. The injection of MPTP for 5 weeks in wild-type mice (MPTP-WT mice), but not in σ 1 R +/− or σ 1 R −/− mice (MPTP- σ 1 R +/− or MPTP- σ 1 R −/− mice), caused motor deficits and ~40% death of dopaminergic neurons in substantia nigra pars compacta with an elevation of N -methyl- d -aspartate receptor (NMDAr) NR2B phosphorylation. The σ 1 R antagonist NE100 or the NR2B inhibitor Ro25-6981 could alleviate the motor deficits and the death of dopaminergic neurons in MPTP-WT mice. By contrast, MPTP- σ 1 R +/− mice treated with the σ 1 R agonist PRE084 or MPTP- σ 1 R −/− mice treated with the NMDAr agonist NMDA appeared to have similar motor deficits and loss of dopaminergic neurons as MPTP-WT mice. The pharmacological or genetic inactivation of σ 1 R suppressed the expression of dopamine transporter (DAT) in substantia nigra, which was corrected by NMDA. The activation of σ 1 R by PRE084 enhanced the DAT expression in WT mice or σ 1 R +/− mice. By contrast, the level of vesicular monoamine transporter 2 (VMAT2) in σ 1 R +/− mice or σ 1 R −/− mice had no difference from WT mice. Interestingly, MPTP-WT mice showed the reduction in the levels of DAT and VMAT2, but MPTP- σ 1 R −/− mice did not. The inactivation of σ 1 R by NE100 could prevent the reduction of VMAT2 in MPTP-WT mice. In addition, the activation of microglia cells in substantia nigra was equally enhanced in MPTP-WT mice and MPTP- σ 1 R −/− mice. The number of activated astrocytes in MPTP- σ 1 R −/− mice was less than that in MPTP-WT mice. The findings indicate that the σ 1 R deficiency through suppressing NMDAr function and DAT expression can reduce MPTP-induced death of dopaminergic neurons and parkinsonism." @default.
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• W1693098624 date "2015-07-23" @default.
• W1693098624 modified "2023-10-12" @default.
• W1693098624 title "Sigma-1 receptor deficiency reduces MPTP-induced parkinsonism and death of dopaminergic neurons" @default.
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• W1693098624 doi "https://doi.org/10.1038/cddis.2015.194" @default.
• W1693098624 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4650739" @default.
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