Age-related differences in brain choline acetyltransferase, cholinesterases and muscarinic receptor sites in two strains of rats.

The age-related changes in choline acetyltransferase (ChAT), cholinesterases (ChE) and muscarinic receptor sites (measured as Bmax of 3H-QNB binding) were evaluated in the cerebral cortex, hippocampus and striatum of Fischer 344 and Wistar male rats at the ages of 3 and 24 months. In the aged Fischer rats there was a significant decline of ChAT (except the hippocampus), ChE and muscarinic receptor densities in the regions analyzed. In the aged Wistar rats cortical and hippocampal ChAT as well as cortical muscarinic receptors remained constant while striatal ChAT, hippocampal and striatal muscarinic receptors decreased significantly; ChE were reduced in all regions analyzed. Factorial analysis of variance (2 strains x 2 ages ANOVA) showed significant strain-related differences in ChAT and muscarinic receptor sites in the three brain areas (about 1.5 times higher levels in the Fischer rats). The same analysis showed significant interactions between strain and age for ChAT and muscarinic receptors in the cerebral cortex, but not in the hippocampus and striatum; no interactions were found for ChE in the regions analyzed. This means that cortical ChAT and muscarinic receptors behave differently in aging in the two strains of rats, i.e., their alterations are strain-specific. Conversely, all other age-related changes (or lack of them for hippocampal ChAT) cannot be considered strain-specific. Moreover, an additional group of 33-month Wistar rats showed a significant decline of cortical muscarinic receptors with respect to 24 month rats but not of other markers in any area. The data underscore the need to consider genotype in the assessment of age-related cholinergic deficits in animal models.