Diminution of nicotinic receptor alpha 3 subunit mRNA expression in aged rat brain

Losses in nicotinic acetylcholine receptors (nAChRs) have been linked to a decline in cognitive function in patients with neurodegenerative diseases, but the impact of normal aging on the different neuronal nicotinic receptor subunits has yet to be fully characterized. The expression pattern of nine nAChR subunits mRNA (alpha2-7 and beta2-4) was investigated in this study in young and aged rat brains, 5 weeks and 30 months old, respectively. Microtissue samples were dissected from brain slices and nAChR subunit mRNA expression was analyzed by reverse transcription polymerase chain reaction (RT-PCR) from eight different brain areas. In several regions, a loss of PCR signal was found for the alpha3, and to a lesser extent, for alpha2 subunit mRNA in aged rat brain. A relative quantification of alpha3 and alpha4 mRNA expression was then carried out in four of these brain regions. A significant diminution of alpha3 expression level was observed in all regions tested while, in comparison, much less modification in alpha4 mRNA was detected. This decrease in alpha3 subunit mRNA may represent a selective degradation of neurons expressing the alpha3 subunit or a diminution of alpha3-containing nAChR subtypes in those neurons during aging.