ENDOCANNABINOID HYDROLYSIS CHANGES IN DIFFERENT SUBCELLULAR FRACTIONS FROM THE CENTRAL NERVOUS SYSTEM BY BETA AMYLOID PEPTIDE AND POLYUNSATURATED FATTY ACIDS

PASCUAL, A.C.; GAVEGLIO, V.L.; GIUSTO, N.M.; PASQUARÉ, S.J.

Puerto Iguazú

Conferencia; 56th International Conference on the Bioscience of Lipids; 2015

International Conference on the Bioscience of Lipids

Endocannabinoid hydrolysis changes in differentsubcellular fractions from the central nervous system by beta amyloid peptideand poliunsaturated fatty acidsPascual, AC#,Gaveglio, VL#, Giusto, NM and Pasquaré, SJ.#Both authors contributed equally to this work.Instituto de InvestigacionesBioquímicas de Bahía Blanca,Universidad Nacional del Sur and Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), 8000Bahía Blanca, Argentina.Email:  pasquare@criba.edu.ar2-arachidonoylglycerol (2-AG) and anandamide (AEA) are the mainendocannabinoids known to date. Among their several functions in the CNS we canhighlight their role as neuroprotective agents. In this respect, endocannabinoidsparticipate in the modulation of numerous cellular and molecular events relatedto neurodegeneration in physiological and pathological aging. Although theendocannabinoid system is well characterized in synaptic endings, its presencehas also been recently observed in nuclei. 2-AG hydrolysis is carried outmainly by monoacylglycerollipase (MAGL) while fatty acid amide hydrolase (FAAH) is responsible for AEAhydrolysis. We have previously demonstrated the regulation of nuclear 2-AGmetabolism by fatty acids in adult rat cerebellum and a deregulation in ratcerebral cortex (CC) endocannabinoid metabolism during aging. The aim of thepresent study was to characterize: i) the modulation of 2-AG hydrolysis byarachidonic acid (AA) and docosahexaenoic acid (DHA) in aged cerebellar nuclei,and ii) 2-AG and AEA hydrolysis in an invitro model of Alzheimer´s Disease (AD) consisting in rat CC synaptosomes preincubatedwith beta amyloid peptide oligomers (mimicking early AD stages) and fibrills(mimicking late AD satages). In contrast to observations in adults, aged animal2-AG hydrolysis was not modified by the presence of AA in cerebellar nuclei. However,DHA decreased this activity probably increasing 2-AG nuclear availability. Thestudies on CC synaptosomes showed that 2-AG and AEA hydrolysis in the early ADmodel diminished, thus indicating that both endocannabinoid levels could beincreased and therefore protect the cell against neurodegenerative processes.Moreover, in the late AD model AEA hydrolysis decreased while 2-AG breakdownhighly increased, thus compromising the neuroprotective role assigned to 2-AG.Our results therefore demonstrate that endocannabinoid metabolism in CNS isdifferentially modulated in aging and also in early and late stages of AD.