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

Maximal phosphoinositide (PI) turnover was examined in the hippocampus of y oung and aged Long-Evans rats that were behaviorally characterized for spat ial learning in the Morris water maze. The type 1 metabotropic glutamate re ceptor (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, G alpha q11, and phospholipase C beta-1 (PLC beta-1) were also meas ured by quantitative Western blotting. The results show that PI turnover me diated by the mGluRs was blunted in the aged rats. The magnitude of the dec rement in PI turnover was also significantly correlated with age-related sp atial memory decline. The decrease in mGluR-mediated PI turnover occurred w ithout changes in the protein level of either the mGluRs or the G-protein c oupled to those receptors, G alpha q11. A significant decrease in the immun oreactivity of PLC beta-1, however, was observed in the hippocampus of aged rats; PLC beta-1 immunoreactivity was significantly correlated with spatia l 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 p art, to a deficiency in the enzyme PLC beta-1. That deficiency may also con tribute to a blunted response in muscarinic stimulation of hippocampal PI t urnover that we previously found in this same study population. An age-rela ted alteration in this signal transduction system may provide a functional basis for cognitive decline independent of any loss of neurons in the hippo campus.