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标题：Dopamine receptor 3 might be an essential molecule in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity
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作者：Yan Chen ; Ying-yin Ni ; Jie Liu 等
期刊名称：BMC Neuroscience
印刷版ISSN：1471-2202
电子版ISSN：1471-2202
出版年度：2013
卷号：14
期号：1
页码：1
DOI：10.1186/1471-2202-14-76
语种：English
出版社：BioMed Central
摘要：Background 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces Parkinson’s disease (PD)-like neurodegeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) via its oxidized product, 1-methyl-4-phenylpyridinium (MPP+), which is transported by the dopamine (DA) transporter into DA nerve terminals. DA receptor subtype 3 (D3 receptor) participates in neurotransmitter transport, gene regulation in the DA system, physiological accommodation via G protein-coupled superfamily receptors and other physiological processes in the nervous system. This study investigated the possible correlation between D3 receptors and MPTP-induced neurotoxicity. A series of behavioral experiments and histological analyses were conducted in D3 receptor-deficient mice, using an MPTP-induced model of PD. Results After the fourth MPTP injection, wild-type animals that received 15 mg/kg per day displayed significant neurotoxin-related bradykinesia. D3 receptor-deficient mice displayed attenuated MPTP-induced locomotor activity changes. Consistent with the behavioral observations, further neurohistological assessment showed that MPTP-induced neuronal damage in the SNpc was reduced in D3 receptor-deficient mice. Conclusions Our study indicates that the D3 receptor might be an essential molecule in MPTP-induced PD and provides a new molecular mechanism for MPTP neurotoxicity.
关键词：Dopamine receptor 3 ; 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity ; Parkinson’s disease