Dynamic Alterations Of Gene Expression Of Nicotinic Acetylcholine Receptor Î±7 Î±4 And Î²2 Subunits In An Acute Mptp-Lesioned Mouse Model
Epidemiologic studies show that the prevalence of Parkinson's disease (PD) is lower in smokers than in nonsmokers. Nicotine, a potent agonist of nicotinic acetylcholine receptors (nAChRs), excites midbrain dopaminergic neurons and this may contribute to the anti-parkinsonian effects. However, the alterations in gene expression of nAChR subunits using an acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse PD model remain unclear. In the present study, we profile the time course of nAChR Î±7, Î±4 and Î²2 subunit expression levels using a comparative RT-PCR approach after acute MPTP injection. The results fall into four categories. (1) MPTP treatment transiently increased nAChR Î±7 (after last injection of MPTP 3 and 24 h), Î±4 and Î²2 (24 h) mRNA expression in the substantia nigra (SN) and striatum. (2) Compared to cortical and hippocampal tissues, this transient increase of nAChR subunit expression specifically occurred in the SN and striatum. (3) In the acute MPTP model, time-courses of altered expression for nAChR Î±7, Î±4 and Î²2 subunits closely mirrored the deficits observed in animal motor activity. (4) Stereological data showed that after administration of MPTP for 24 h, there was a robust astrogliosis in the SN associated with significant dopaminergic neurodegeneration. These changes followed or paralleled MPTP-induced elevation in the levels of Î±7, Î±4 and Î²2 mRNAs. Collectively, our results demonstrate that nAChRs are important targets in the MPTP neurotoxic process. These data suggest that therapeutic strategies targeted toward nAChR Î±7, Î±4 and Î²2 subunits may have potential for developing new treatments for PD. Â© 2011 Elsevier Ireland Ltd.
Digital Object Identifier (DOI)
Hu, Jun; Zhu, Chenlei; Liu, Yuan; Wang, Fang; Huang, Zuhu; Fan, Weimin; and Wu, Jie, "Dynamic Alterations Of Gene Expression Of Nicotinic Acetylcholine Receptor Î±7 Î±4 And Î²2 Subunits In An Acute Mptp-Lesioned Mouse Model" (2011). Neurobiology. 417.