Subunit and region-specific decreases in nicotinic acetylcholine receptor mRNA in the aged rat brain

We have investigated possible changes in the mRNA levels for several alpha and beta subunits of the nicotinic acetylcholine receptor (nAChR) and the level of binding for nicotinic ligands in 7- to 32-month-old rats. alpha 4 and beta 2, and to a lesser extent alpha 6 and beta 3, mRNA levels showed decreases between 20 and 30% at 29 months of age which in some areas reached 50% at 32 months of age, alpha 7 showed a small increase from 7 to 14 months and then a progressive decrease from 14 to 32 months down to the 7-month levels. H-3-epibatidine binding did not significantly change from 7 to 32 months of age in rat tel- and diencephalon. Binding in the substantia nigra was exceptional in that it showed a significant decrease starting from 23 months of age. I-125-alpha-bungarotoxin binding showed a pattern of change which roughly paralleled that of alpha 7 mRNA. These findings show that an alteration in some steps of nAChR biosynthesis takes place during aging, which may be related to functional changes in nicotinic transmission. (C) 1999 Elsevier Science Inc. All rights reserved.