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The Journal of Neuroscience, November 1, 1999, 19(21):9604-9610

Metabotropic Glutamate Receptor-Mediated Hippocampal Phosphoinositide Turnover Is Blunted in Spatial Learning-Impaired Aged Rats

Michelle M. Nicolle1, Paul J. Colombo2, Michela Gallagher3, and Michael McKinney1

1 Mayo Clinic, Department of Pharmacology, Jacksonville, Florida 32224, 2 Tulane University, Department of Psychology, New Orleans, Louisiana 70118, and 3 Johns Hopkins University, Department of Psychology, Baltimore, Maryland 21218

Maximal phosphoinositide (PI) turnover was examined in the hippocampus of young and aged Long-Evans rats that were behaviorally characterized for spatial learning in the Morris water maze. The type 1 metabotropic glutamate receptor (mGluR) agonist 1S,3R ACPD was used to stimulate PI turnover and to determine the EMAX for each rat. Protein levels in hippocampus for type 1 mGluRs, Galpha q11, and phospholipase Cbeta -1 (PLCbeta -1) were also measured by quantitative Western blotting. The results show that PI turnover mediated by the mGluRs was blunted in the aged rats. The magnitude of the decrement in PI turnover was also significantly correlated with age-related spatial memory decline. The decrease in mGluR-mediated PI turnover occurred without changes in the protein level of either the mGluRs or the G-protein coupled to those receptors, Galpha q11. A significant decrease in the immunoreactivity of PLCbeta -1, however, was observed in the hippocampus of aged rats; PLCbeta -1 immunoreactivity was significantly correlated with spatial learning only when the young and aged rats were considered together. The decrement in mGluR-mediated signal transduction in the hippocampus that is related to cognitive impairment in aging may be attributable, at least in part, to a deficiency in the enzyme PLCbeta -1. That deficiency may also contribute to a blunted response in muscarinic stimulation of hippocampal PI turnover that we previously found in this same study population. An age-related alteration in this signal transduction system may provide a functional basis for cognitive decline independent of any loss of neurons in the hippocampus.

Key words: phosphoinositide; hippocampus; aging; spatial memory; metabotropic glutamate receptor; Galpha q11; phospholipase Cbeta -1.


Copyright © 1999 Society for Neuroscience  0270-6474/99/19219604-07$05.00/0




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