Quality of Life and a Surveillant Endocannabinoid System.

The endocannabinoid system (ECS) is an important brain modulatory network. ECS regulates brain homeostasis throughout development, from progenitor fate decision to neuro- and gliogenesis, synaptogenesis, brain plasticity and circuit repair, up to learning, memory, fear, protection, and death. It is a major player in the hypothalamic-peripheral system-adipose tissue in the regulation of food intake, energy storage, nutritional status, and adipose tissue mass, consequently affecting obesity. Loss of ECS control might affect mood disorders (anxiety, hyperactivity, psychosis, and depression), lead to drug abuse, and impact neurodegenerative (Alzheimer's, Parkinson, Huntington, Multiple, and Amyotrophic Lateral Sclerosis) and neurodevelopmental (autism spectrum) disorders. Practice of regular physical and/or mind-body mindfulness and meditative activities have been shown to modulate endocannabinoid (eCB) levels, in addition to other players as brain-derived neurotrophic factor (BDNF). ECS is involved in pain, inflammation, metabolic and cardiovascular dysfunctions, general immune responses (asthma, allergy, and arthritis) and tumor expansion, both/either in the brain and/or in the periphery. The reason for such a vast impact is the fact that arachidonic acid, a precursor of eCBs, is present in every membrane cell of the body and on demand eCBs synthesis is regulated by electrical activity and calcium shifts. Novel lipid (lipoxins and resolvins) or peptide (hemopressin) players of the ECS also operate as regulators of physiological allostasis. Indeed, the presence of cannabinoid receptors in intracellular organelles as mitochondria or lysosomes, or in nuclear targets as PPARγ might impact energy consumption, metabolism and cell death. To live a better life implies in a vigilant ECS, through healthy diet selection (based on a balanced omega-3 and -6 polyunsaturated fatty acids), weekly exercises and meditation therapy, all of which regulating eCBs levels, surrounded by a constructive social network. Cannabidiol, a diet supplement has been a major player with anti-inflammatory, anxiolytic, antidepressant, and antioxidant activities. Cognitive challenges and emotional intelligence might strengthen the ECS, which is built on a variety of synapses that modify human behavior. As therapeutically concerned, the ECS is essential for maintaining homeostasis and cannabinoids are promising tools to control innumerous targets.

Maternal omega-3 intake differentially affects the endocannabinoid system in the progeny`s neocortex and hippocampus: Impact on synaptic markers.

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.

Fighting Oxidative Stress: Increased Resistance of Male Rat Cerebellum at Weaning Induced by Low Omega 6/Omega 3 Ratio in a Protein-Deficient Diet.

The cerebellum is vulnerable to malnutrition effects. Notwithstanding, it is able to incorporate higher amount of docosahexaenoic acid (DHA) than the cerebral cortex (Cx) when low n-6/n-3 fatty acid ratio is present in a multideficient diet. Considering importance of DHA for brain redox balance, we hypothesize that this cerebellum feature improves its antioxidant status compared to the Cx. A chronic malnutrition status was induced on dams before mating and kept until weaning or adulthood (offspring). A group nutritionally rehabilitated from weaning was also analyzed. Morphometric parameters, total-superoxide dismutase (t-SOD) and catalase activities, lipoperoxidation (LP), nitric oxide (NO), reduced (GSH) and oxidized (GSSG) glutathione, reactive oxygen species (ROS), and reduced nicotinamide adenine dinucleotide/phosphate levels were assessed. Both ROS and LP levels were increased (∼53 %) in the Cx of malnourished young animals while the opposite was seen in the cerebellum (72 and 20 % of the control, respectively). Consistently, lower (∼35 %) and higher t-SOD (∼153 %) and catalase (CAT) (∼38 %) activities were respectively detected in the Cx and cerebellum compared to the control. In malnourished adult animals, redox balance was maintained in the cerebellum and recovered in the Cx (lower ROS and LP levels and higher GSH/GSSG ratio). NO production was impaired by malnutrition at either age, mainly in the cerebellum. The findings suggest that despite a multinutrient deficiency and a modified structural development, a low dietary n-6/n-3 ratio favors early antioxidant resources in the male cerebellum and indicates an important role of astrocytes in the redox balance recovery of Cx in adulthood.