Development and Aging of Cholinergic Synapses

Abstract

The relationships among biochemical parameters of cholinergic metabolism in autonomic nerve terminals in the chick iris were determined throughout the life span of the animal, following in vitro incubation with [³H]choline (Ch). Choline accumulation, acetylcholine (ACh) content and ACh turnover increased steadily up to the adult stage (3 months – 1 year) and then declined in aged animals (5 years). These changes appeared to reflect the activity and the state of the cholinergic innervation of the iris. Other changes which occurred with age included a steady decline in the ratio of Ch to ACh, and a decrease in the concentration of endogenous Ch relative to [³H]Ch taken up from the medium. However, the ratio of [³H]Ch to [³H]ACh did not vary significantly with age from 10 days of incubation (d.i.) up to 5 years. Uptake of [³H]Ch and synthesis of [³H] ACh were both inhibited by low temperature (27°C), ouabain (1CH M), hemicholinium (HC-3) (5 x 10^–5M) and low Na⁺ at both 3 months and 5 years. Low temperature and ouabain, however, did not inhibit [³H]ACh formation to the same extent as HC-3 and low Na⁺. Cholinesterase inhibitors appeared to inhibit [³H]Ch uptake by increasing intracellular ACh, confirming previous reports. These observations can be taken to support our view that the characteristics of Ch uptake do not develop and age simultaneously in cholinergic endings. In conclusion, our results indicate that the turnover rate of ACh is slowed in aging autonomic nerve terminals, although the rate of synthesis of [³H]ACh from taken up [³H]Ch is unvaried. The present findings on Ch metabolism taken together with our previous results on ACh and Ch content, Ch uptake, and enzymatic activities confirm our view of the peripheral terminals of the autonomic neuron as a site of specific developmental changes and of selective vulnerability to aging processes.