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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2011-4-15
pubmed:abstractText
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 ?7, ?4 and ?2 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 ?7 (after last injection of MPTP 3 and 24 h), ?4 and ?2 (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 ?7, ?4 and ?2 subunits closely mirrored the deficits observed in animal motor activity. (4) Stereological data showed that after administration of MPTP for 24h, 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 ?7, ?4 and ?2 mRNAs. Collectively, our results demonstrate that nAChRs are important targets in the MPTP neurotoxic process. These data suggest that therapeutic strategies targeted toward nAChR ?7, ?4 and ?2 subunits may have potential for developing new treatments for PD.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1872-7972
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
2
pubmed:volume
494
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
232-6
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Dynamic alterations of gene expression of nicotinic acetylcholine receptor ?7, ?4 and ?2 subunits in an acute MPTP-lesioned mouse model.
pubmed:affiliation
Department of Orthopedics, the First Affiliated Hospital of Nanjing Medical University, Guang Zhou Road 300, Nanjing 210029, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't