AGING DIMINISHES SEROTONIN-STIMULATED ARACHIDONIC-ACID UPTAKE AND CHOLINERGIC RECEPTOR-ACTIVATED-ARACHIDONIC ACID RELEASE IN RAT-BRAIN CORTEX MEMBRANE

Synaptoneurosomal and synaptosomal fractions from the brain cortex of adult (4-month-old) and aged (27-month-old) rats were used for studies on the uptake and subsequent release of [C-14]arachidonic acid ([C-14 ]AA) from brain lipids. The incorporation of AA and the pattern of its uptake into lipids of the aged brain cortex synaptoneurosomes and syn aptosomes were not significantly different when compared with those in the adult brain cortex fractions. Serotonin (5-HT), at 10 mu M to 1 m M in the presence of pargyline and the agonist of the 5-HT1A receptor, buspirone, stimulated AA uptake into membrane lipids, mainly into pho sphatidylinositol, by about 40% exclusively in adult brain synaptoneur osomes. Aging significantly diminished the effect of 5-HT on AA uptake . Synaptoneurosomal and synaptosomal fractions prelabeled with [C-14]A A were used subsequently for investigation of voltage-dependent, musca rinic and 5-HT receptor-mediated AA release. Aging diminished markedly carbachol-stimulated Ca2+-dependent AA liberation from membrane lipid s of synaptoneurosomes and synaptosomes. Moreover, aging decreased vol tage-dependent and 5-HT2 receptor-mediated AA release. These results s how that aging affects receptor-dependent AA uptake and pre- and posts ynaptic receptor-mediated AA release. These modulations of AA incorpor ation and release in aged brain may be of pathophysiological significa nce, in View of the importance of these processes for signal transmiss ion in the brain. The changes of receptor-dependent processes of deacy lation and reacylation may be responsible for alteration in the functi on of neuronal cells and may affect learning and memory ability and br ain plasticity during aging.