Synaptic Aging and Carnitine

Age-related changes in neuronal functions were examined in terms of cholinergic synaptic transmission as an initial step. The synthetic capacity of acetylcholine was found to remain unchanged during the lifespan of mouse. This finding has revised the existing concept that acetylcholine synthesis is decreased in aging. The present study has revealed that the density of voltage-dependent calcium channels in synaptic plasma menbranes is decreased to reduce Ca2+ influx into synapses, resulting in the decreased release of acetylcholine.   The hypofunction of cholinergic synapses occuring in aging was attempted to be restored in the socond place. Sialic acid-containing compounds including gangliosides and synthetic ganglioside analogues were found to facilitate the acetylcholine release by increasing Ca2+ influx or choline uptake. On the other hand, acethl-L-carnitine was shown to serve as a donor of acetyl residues to increase acetylcholine synthesis. This carnitine derivative may be a good candidate for an enhancer of cholinergic transmission and for anti-brain aging supplement.