Age-related changes in receptor-mediated and depolarization-induced phosphatidylinositol turnover in mouse brain

Abstract

The effect of aging on receptor- and G-protein-activated and on depolarization-induced phosphoinositide (PI) hydrolysis was examined in mechanically dissociated neurons from female NMRI mice. Additionally, age-dependent changes in Ca 2+ homeostasis, i.e. changes in basal intracellular calcium ([Ca 2+] i) and in depolarization-induced rise in [Ca 2+] i were investigated. No age-related differences in PI hydrolysis were found after stimulation of muscarinic cholinergic, α 1 , serotonin and quisqualate receptors coupled to the phosphoinositide-phospholipase C (PI-PLC) system. PI hydrolysis following stimulation with AMPA ((RS)-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) revealed a significantly increased response in aged animals. Activation of G-proteins with NaF also induced a higher inositol monophosphate (InsP 1) accumulation in aged mice. Moreover, InsP 1 accumulation due to PLC activation by increased [Ca 2+] i after depolarization with KCl was significantly increased in neurons from aged animals. Investigations about age-related changes in Ca 2+ homeostasis revealed lower basal [Ca 2+] i and lower rise in [Ca 2+] i after depolarization with KCl. The data indicate that receptor-mediated and depolarization-induced PI hydrolysis are differentially affected by aging. Decreased availability of [Ca 2+] i in aged animals may enhance the sensitivity of Ca 2+-activated mechanisms. This may explain increased KCl- and AMPA-induced InsP 1 accumulation whereas receptor-coupled PLC activation is less affected.