Choline acetyltransferase activity and muscarinic binding in brain regions of aging fischer-344 rats

Abstract

Muscarinic receptor binding and choline acetyltransferase (EC 2.3.1.6.) activity were assayed in three brain regions of 4-, 12- and 24-month-old Fischer-344 rats. Statistically significant age differences in cholinergic parameters were observed in each region. The affinity for [ 3H]quinuclidinyl benzilate increased in the cortex (24 vs 12 and 4 months), but B max decreased in the cortex (24 vs 12 vs 4 months), striatum (24 vs 12 vs 4 months) and hippocampus (24 vs 12 and 24 vs 4). Assays of carbamylcholine inhibition of [ 3H]quinuclidinyl benzilate binding in the hippocampus showed that high affinity agonist binding increased with age (24 vs 12 and 4 months), and the percentage of muscarinic binding to high affinity agonist sites decreased (24 vs 12 vs 4 months). In addition, the affinity of the agonist oxotremorine for muscarinic binding sites also increased in the hippocampus (12 and 24 vs 4 months). Although the K m of choline acetyltransferase for choline chloride did not change in any region tested, the K m for acetyl coenzyme A decreased in the hippocampus (24 vs 12 months), but increased (4 vs 12 months) and then decreased (12 vs 24 months) in the striatum. Statistically significant age-related declines in V max for choline acetyltransferase were noted in the striatum (24 < 12 < 4 months), but no age differences in this parameter were observed in the cortex or the hippocampus. Statistically significant positive correlations between V max for choline acetyltransferase and B max for [ 3H]quinuclidinyl benzilate binding were observed in each of the brain regions of 4-, 12- and 24-month-old rats. The findings have implications for use of the Fischer-344 male rat as an animal model of aging and age-related disorders of the human brain, including dementia of the Alzheimer type.