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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, G q11, and phospholipase C -1
(PLC-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, Gq11. A significant decrease in the immunoreactivity of
PLC-1, however, was observed in the hippocampus of aged rats;
PLC-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 PLC-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; Gq11; phospholipase C-1.
Copyright © 1999 Society for Neuroscience 0270-6474/99/19219604-07$05.00/0
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