Alterations with aging and ischemia in nicotinic acetylcholine receptor subunits alpha4 and beta2 messenger RNA expression in postmortem human putamen. Implications for susceptibility to parkinsonism.
Nicotine activates the dopaminergic system and acts to alleviate hypokinetic disorders (parkinsonism). The frequency of parkinsonism increases with age and is sometimes associated with multiple small infarcts (status lacunaris) in the putamen. To investigate changes with aging in control cases free from neurological disease and changes in cases with multiple small infarcts (status lacunaris) in the putamen, the present study determined nicotinic acetylcholine receptor (nAChR) subunit alpha4 and beta2 messenger RNA (mRNA) expression in the postmortem human putamen using the reverse transcription-polymerase chain reaction (RT-PCR). In controls, alpha4 subunit mRNA expression was unaltered, but beta2 subunit mRNA expression decreased significantly with age. In cases with status lacunaris, both beta2 and alpha4 subunit mRNA expressions were significantly lower than in the control cases. The reduction in beta2 mRNA expression alone, or in both alpha4 and beta2 mRNA expressions, suggests a reduction in functional nAChRs in the putamen, which may in part explain the susceptibility to hypokinetic disorders of the elderly and subjects with ischemic damage in the striatum.
Tohgi
H
H
Department of Neurology, Iwate Medical University, 19-1 uchimaru, Morioka, Iwate 020, Japan.
Utsugisawa
K
K
Yoshimura
M
M
Nagane
Y
Y
Mihara
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D000704:Analysis of Variance; D016022:Case-Control Studies; D002544:Cerebral Infarction / Q000378:metabolism; D004198:Disease Susceptibility; D005260:Female; D006801:Humans; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000378:metabolism; D010446:Peptide Fragments / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D011699:Putamen / Q000098:blood supply / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis*; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000235:genetics*; D014158:Transcription, Genetic
D010446:Peptide Fragments; D012333:RNA, Messenger; D011978:Receptors, Nicotinic