Decrease of Acetylcholine Release from Cortical Slices in Aged Rats: Investigations into Its Reversal by Phosphatidylserine

Abstract

The release of total acetylcholine (ACh) and [3H]ACh was investigated in electrically stimulated cortical slices prepared from 4- and 18-month-old male Wistar rats. The slices were prelabeled with [3H]choline ([3H]Ch) and perfused with Krebs solution containing physostigmine. Total ACh was measured and the nature of the tritium efflux identified by HPLC. The total tritium content in the slices at the end of the incubation period was half as great in the old as in young rats. A linear relationship was found between stimulation frequencies (2, 5, and 10 Hz) and fractional [3H]ACh release in both young and old rats. In the latter the release was significantly smaller. At 10 Hz stimulation frequency the ratio between the two 2-min stimulation periods, S2/S1, was higher in the 18-month-old rats than in the young rats. Specific activity of the evoked ACh release was significantly smaller in S2 than in S1 in 4-month-old rats only. These findings indicate that the young synthetize ACh from endogenous unlabeled Ch more than older rats. In 18-month-old rats both the evoked total ACh and [3H]ACh release, expressed as picograms per minute, showed an approximately 50% decrease in both S1 and S2 stimulation periods, with no significant difference in specific activity. Phosphatidylserine (PtdSer) administration (15 mg/kg, i.p. daily) for 1 week to 18-month-old rats prevented the reduction in total evoked ACh release but not the reduction in evoked [3H]ACh release. The specific activity of ACh release was therefore significantly smaller than that of the young and untreated old rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Cellular Acetylcholine Content and Neuronal Differentiation

“…After two further washings, the cells were collected in 140 jil of 0.014 M citrate buffer prewarmed at 100°Cand homogenized in a glass-glass homogenizer. ACh was determined in the homogenates after HPLC separation, following the method of Vannucchi et al (1990).…”

Acetylcholine and muscarinic receptor function in cerebral cortex of diabetic young and old male Wistar rats and the role of muscarinic receptors in calcium release from pancreatic islets

“…Impairment in the ability to synthesize and release ACh has been consistently reported in aged rodent cortex (Vannucchi et al 1990). The activity of AChE, the degradative enzyme of cholinergic system, in the cerebral cortex of 90 weeks old control group decreased significantly compared to 7 weeks old control with significant increase in the K m .…”

“…The cholinergic innervation of the cerebral cortex has been extensively investigated because of its role in arousal, learning and memory (Bartus et al 1985;McCormick 1989McCormick , 1992Olton et al 1991;Voytko et al 1994). Studies in rodents have shown a consistent decline in cortical ACh synthesis and release during ageing (Gibson et al 1981;Araujo et al 1990;Vannucchi et al 1990). Also, memory decline during ageing has been extensively documented in rodents (Ingram et al 1981), nonhuman primates (Presty et al 1987), and humans (Rowe and Kahn 1987).…”

Age-dependent decrease in the affinity of muscarinic M1 receptors in neocortex of rhesus monkeys.

“…Impairment in the ability to synthesize and release ACh has been consistently reported in aged rodent cortex (e.g., refs. [7][8][9]. Electrophysiological experiments in the hippocampus of old rats showed impairment in neuronal response to local application of ACh (but not of glutamate) without consistent changes in receptor number (1).…”

“…Although the aging process seems to impinge on several neurotransmitter systems, special emphasis has been placed on the role of the cortical cholinergic innervation in geriatric memory dysfunction (6). Studies in rodents have shown a consistent decline in cortical acetylcholine (ACh) synthesis and release during aging (7)(8)(9), although little or no change occurs in cortical choline acetyltransferase activity (1,8,6,10). Further, the cholinergic basal forebrain neurons that project to the cortex undergo an age-related decrease in size though their number is apparently not diminished (11).…”