Age-related changes in neuronal nicotinic acetylcholine receptor subunit alpha4 expression are modified by long-term nicotine administration.

The distribution of the neuronal nicotinic acetylcholine receptor subunit alpha4 (nAChRalpha4) in the brains of young (2-4 months) or aged (24-28 months) CBA/J mice was examined using immunohistochemical staining. Anti-nAChRalpha4 immunoreactivity corresponded with nAChRalpha4 RNA expression and high-affinity [3H]nicotine binding. Immunostaining in aged mice relative to that in young animals was diminished in the medial septum and diagonal band but was unchanged in the globus pallidus and substantia nigra. The staining of neurons was almost completely absent in the hippocampus of aged animals. The oral administration of nicotine to aged animals for 6 weeks did not alter nAChRalpha4 expression relative to that in aged controls. However, the long-term delivery of nicotine (11 months) to 14-month-old animals corresponded with the highly specific preservation of nAChRalpha4 expression in some neurons of the dentate gyrus region and in neurite processes of remaining neurons of the hippocampal CA1 region. These results support the conclusion that the loss of nAChRalpha4 expression occurs in key cholinergic regions during normal aging. Furthermore, sustained long-term nicotine delivery may promote highly region-specific retention of nAChR expression, but only if initiated before normal age-related receptor decline.