THE DEVELOPMENT OF AGE-RELATED DEFICITS IN SEVERAL PRESYNAPTIC PROCESSES ASSOCIATED WITH BRAIN [H-3] ACETYLCHOLINE-RELEASE

Isolated nerve terminals were prepared from the neocortices and striat e cortices of Fischer 344 rats from 6 to 26 months of age and then ass ayed for release of newly synthesized [H-3]acetylcholine (ACh) trigger ed by secretagogues with different mechanisms of action: 35 mM K+, 10 mu M veratridine and 5 mu M A23187. Secretagogue-induced release of ne wly synthesized [H-3]ACh decreased with age in both brain regions, wit h reductions in A23187-induced release paralleling those seen with dep olarizing agents. This observation was consistent with the hypothesis that aging attenuates the release-triggering ability of calcium ions c oincident with or before it affects voltage-sensitive calcium influx. In neocortex, phorbol-stimulated translocation of protein kinase C (PK C) activity was attenuated in isolated nerve terminals concomitantly w ith A23187-induced release deficits. These results suggest that one of the earliest deficits in the ACh-release process may involve intracel lular calcium potency, which may be associated with the onset of funct ional PKC deficits. Both brain regions also displayed gradual, age-rel ated reductions in [H-3]ACh synthesis, but this effect was more pronou nced in the striatum. Choline acetyltransferase (CAT) activity decreas ed only in the striatum with aging.