Anandamide hydrolysis is modulated by cannabinoid receptors in aged rat cerebral cortex

Abstract

Fatty acid amide hydrolase (FAAH) has been reported as the main enzyme involved in anandamide (AEA) hydrolysis. Among the multiple functions of AEA we can highlight the regulation of synaptic plasticity and its antiinflammatory role. The aim of this study was to analyze AEA hydrolysis in cerebral cortex (CC) subcellular fractions during physiological aging and its regulation by cannabinoid receptors (CBR). CC membrane and synaptosomal fractions from adult (3 mo) and aged (28 mo) rats were isolated by differential centrifugation and the synaptosomal fraction was purified in ficoll gradients. AEA hydrolysis was assayed using [3H]AEA and its product was quantified from the aqueous phase. Aging differently modulated FAAH by increasing and decreasing its activity in membranes and synaptosomes, respectively. In the presence of FAAH specific inhibitor URB-597 AEA hydrolysis activity assay corroborates that AEA is the main enzyme involved in CC AEA degradation. CBR agonists decreased FAAH activity, mainly by CB2R, thus increasing CC AEA availability. Our results show that while aged CC membrane AEA availability decreases, possibly compromising its antiinflammatory functions, the endocannaboid level in synaptosomes increases, protecting against the synaptic dysfunction inflicted by aging. AEA availability could be increased by targeting CB2R, thus improving brain damage caused by aging