Metabotropic glutamate receptor-mediated hippocampal phosphoinositide turnover is blunted in spatial learning-impaired aged rats

Michelle M. Nicolle, Paul J. Colombo, Michela Gallagher, Michael McKinney

Research output: Contribution to journalArticle

Abstract

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 E(max) for each rat. Protein levels in hippocampus for type 1 mGluRs, Gαq11, and phospholipase Cβ-1 (PLCβ-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, Gαq11. A significant decrease in the immunoreactivity of PLCβ-1, however, was observed in the hippocampus of aged rats; PLCβ-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 PLCβ-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.

Original languageEnglish (US)
Pages (from-to)9604-9610
Number of pages7
JournalJournal of Neuroscience
Volume19
Issue number21
StatePublished - Nov 1 1999

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Metabotropic Glutamate Receptors
Phosphatidylinositols
Type C Phospholipases
Hippocampus
Signal Transduction
Excitatory Amino Acid Agonists
Long Evans Rats
GTP-Binding Proteins
Cholinergic Agents
Spatial Learning
Proteins
Western Blotting
Neurons
Water
Enzymes
Population

Keywords

  • Aging
  • Gαq 11
  • Hippocampus
  • Metabotropic glutamate receptor
  • Phosphoinositide
  • Phospholipase Cβ-1
  • Spatial memory

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Metabotropic glutamate receptor-mediated hippocampal phosphoinositide turnover is blunted in spatial learning-impaired aged rats. / Nicolle, Michelle M.; Colombo, Paul J.; Gallagher, Michela; McKinney, Michael.

In: Journal of Neuroscience, Vol. 19, No. 21, 01.11.1999, p. 9604-9610.

Research output: Contribution to journalArticle

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