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Maternal omega-3 intake differentially affects the endocannabinoid system in the progeny`s neocortex and hippocampus: Impact on synaptic markers
Affiliation:1. Instituto de Biofísica Carlos Chagas Filho (IBCCF), Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil;2. Instituto de Nutrição, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil;3. Instituto de Nutrição Josué de Castro (INJC), Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil;4. Endocannabinoid Research Group, Istituto di Chimica Biomolecolare (ICB), Consiglio Nazionale delle Ricerche (CNR), Pozzuoli (NA), Italy;5. Grupo de Bioinformática e prospecção molecular, Laboratório de Imunopatologia Keizo Asami, Universidade Federal de Pernambuco, Recife, Pernambuco, Brazil;6. Departamento de Bioquímica, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil;7. Departamento de Fisiologia e Farmacologia, Centro de Biociências, Universidade Federal de Pernambuco, Recife, Pernambuco, Brazil;8. Canada Exellence Research Chair on the Microbiome-Endocannabinoidome Axis in Metabolic Health, CRIUCPQ and NUTRISS-INAF Universitè Laval, Quebec City, Canada;1. Instituto de Fisiología Experimental (IFISE)-CONICET, Facultad de Ciencias Bioquímicas y Farmacéuticas, UNR, Rosario, Argentina;2. Área Morfología, Facultad de Ciencias Bioquímicas y Farmacéuticas, UNR, Rosario, Argentina;3. CAECIHS, Universidad Abierta Interamericana, Rosario, Argentina;1. National Institute of Nutrition, Indian Council of Medical Research, Hyderabad, India;2. Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Norway;1. Laboratorio de Fisiología de la Preñez y el Parto, Centro de Estudios Farmacológicos y Botánicos (CEFyBO-UBA/CONICET). Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina;2. Departamento de Química Biológica. Intendente Güiraldes, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina;3. Instituto de Química Biológica. Intendente Güiraldes, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina;1. Department of Biochemistry, Memorial University of Newfoundland and Labrador, St. John''s, Newfoundland and Labrador A1B 3X9, Canada
Abstract:Omega-3 (n-3) polyunsaturated fatty acids (PUFA) and the endocannabinoid system (ECS) modulate several functions through neurodevelopment including synaptic plasticity mechanisms. The interplay between n-3PUFA and the ECS during the early stages of development, however, is not fully understood. This study investigated the effects of maternal n-3PUFA supplementation (n-3Sup) or deficiency (n-3Def) on ECS and synaptic markers in postnatal offspring. Female rats were fed with a control, n-3Def, or n-3Sup diet from 15 days before mating and during pregnancy. The cerebral cortex and hippocampus of mothers and postnatal 1-2 days offspring were analyzed. In the mothers, a n-3 deficiency reduced CB1 receptor (CB1R) protein levels in the cortex and increased CB2 receptor (CB2R) in both cortex and hippocampus. In neonates, a maternal n-3 deficiency reduced the hippocampal CB1R amount while it increased CB2R. Additionally, total GFAP isoform expression was increased in both cortex and hippocampus in neonates of the n-3Def group. Otherwise, maternal n-3 supplementation increased the levels of n-3-derived endocannabinoids, DHEA and EPEA, in the cortex and hippocampus and reduced 2-arachidonoyl-glycerol (2-AG) concentrations in the cortex of the offspring. Furthermore, maternal n-3 supplementation also increased PKA phosphorylation in the cortex and ERK phosphorylation in the hippocampus. Synaptophysin immunocontent in both regions was also increased. In vitro assays showed that the increase of synaptophysin in the n-3Sup group was independent of CB1R activation. The findings show that variations in maternal dietary omega-3 PUFA levels may impact differently on the ECS and molecular markers in the cerebral cortex and hippocampus of the progeny.
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