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AGE-DEPENDENT CHANGES IN RECEPTOR-STIMULATED PHOSPHOINOSITIDE TURNOVER IN THE RAT HIPPOCAMPUS
Citation:
Tandon, P., W. Mundy, S. Ali, K. Nanry, B. Rogers, AND H. Tilson. AGE-DEPENDENT CHANGES IN RECEPTOR-STIMULATED PHOSPHOINOSITIDE TURNOVER IN THE RAT HIPPOCAMPUS. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-92/253.
Description:
To study the changes in the hippocampal cholinergic system of chronologically old and behaviorally impaired animals, old (21 months of age) and young (3 months of age) male, Fischer-344 rats were used. The aged animals were tested on a reference memory task (Morris water maze) and found to be functionally impaired as compared to the young controls. Carbachol-stimulated phosphoinositide metabolism was measured in hippocampal slices from young and old rats. Slices were prelabeled with 3H-inositol for 120 min and subjected to muscarinic stimulation in the presence of lithium. Following extraction of the slices with acidified solvent mixture, the inositolphosphate5 present in the aqueous fraction were isolated by ion exchange chromatography. Receptor-stimulated release of inositolphosphates (IPs) was found o be increased in the hippocampus of older animals. 1P release was also found to be greater in the presence of sodium fluoride in older animals. This age related enhancement of IP release was in contrast to the decrease in acetyltransferase (CHAT) activity in the hippocampus. We postulate that alterations in the G-protein coupling with the muscarinic receptor leads to an increase in the phosphoinositide turnover in part as a compensatory mechanism for neuronal cell death and reduced transmitter levels.