Search results for "endocannabinoid"

Cell Type-Specific Tandem Affinity Purification of the Mouse Hippocampal CB1 Receptor-Associated Proteome

2016

G protein coupled receptors (GPCRs) exert their effects through multiprotein signaling complexes. The cannabinoid receptor type 1 (CB1) is among the most abundant GPCRs in the mammalian brain and involved in a plethora of physiological functions. We used a combination of viral-mediated cell type-specific expression of a tagged CB1 fusion protein (CB1-SF), tandem affinity purification (TAP) and proteomics on hippocampal mouse tissue to analyze the composition and differences of CB1 protein complexes in glutamatergic neurons and in GABAergic interneurons. Purified proteins underwent tryptic digestion and were identified using deep-coverage data-independent acquisition with ion mobility separa…

Physical Activity and Brain Health.

2019

Physical activity (PA) has been central in the life of our species for most of its history, and thus shaped our physiology during evolution. However, only recently the health consequences of a sedentary lifestyle, and of highly energetic diets, are becoming clear. It has been also acknowledged that lifestyle and diet can induce epigenetic modifications which modify chromatin structure and gene expression, thus causing even heritable metabolic outcomes. Many studies have shown that PA can reverse at least some of the unwanted effects of sedentary lifestyle, and can also contribute in delaying brain aging and degenerative pathologies such as Alzheimer’s Disease, diabetes, and multiple s…

2018

Obesity is one of the major public health issues, and its prevalence is steadily increasing all the world over. The endocannabinoid system (ECS) has been shown to be involved in the intake of palatable food via activation of cannabinoid 1 receptor (CB1R). However, the involvement of lingual CB1R in the orosensory perception of dietary fatty acids has never been investigated. In the present study, behavioral tests on CB1R−/− and wild type (WT) mice showed that the invalidation of Cb1r gene was associated with low preference for solutions containing rapeseed oil or a long-chain fatty acid (LCFA), such as linoleic acid (LA). Administration of rimonabant, a CB1R inverse agonist, in mice also br…

Endocannabinoid LTD in Accumbal D1 Neurons Mediates Reward-Seeking Behavior

2020

Summary The nucleus accumbens (NAc) plays a key role in drug-related behavior and natural reward learning. Synaptic plasticity in dopamine D1 and D2 receptor medium spiny neurons (MSNs) of the NAc and the endogenous cannabinoid (eCB) system have been implicated in reward seeking. However, the precise molecular and physiological basis of reward-seeking behavior remains unknown. We found that the specific deletion of metabotropic glutamate receptor 5 (mGluR5) in D1-expressing MSNs (D1miRmGluR5 mice) abolishes eCB-mediated long-term depression (LTD) and prevents the expression of drug (cocaine and ethanol), natural reward (saccharin), and brain-stimulation-seeking behavior. In vivo enhancement…

Changes in the Peripheral Endocannabinoid System as a Risk Factor for the Development of Eating Disorders

2017

BACKGROUND AND OBJECTIVE Eating Disorder (ED) is characterized by persistently and severely disturbed eating behaviours. They arise from a combination of long-standing behavioural, emotional, psychological, interpersonal, and social factors and result in insufficient nutrient ingestion and/or adsorption. The three main EDs are: anorexia nervosa, bulimia nervosa, and binge eating disorder. We review the role of peripheral endocannabinoids in eating behaviour. DISCUSSION The neuronal pathways involved in feeding behaviours are closely related to catecholaminergic, serotoninergic and peptidergic systems. Accordingly, feeding is promoted by serotonin, dopamine, and prostaglandin and inhibited b…

Diacylglycerol lipase alpha in astrocytes is involved in maternal care and affective behaviors.

2021

Genetic deletion of cannabinoid CB1 receptors or diacylglycerol lipase alpha (DAGLa), the main enzyme involved in the synthesis of the endocannabinoid (eCB) 2-arachidonoylglycerol (2-AG), produced profound phenotypes in animal models of depression-related behaviors. Furthermore, clinical studies have shown that antagonists of CB1 can increase the incidence and severity of major depressive episodes. However, the underlying pathomechanisms are largely unknown. In this study, we have focused on the possible involvement of astrocytes. Using the highly sensitive RNAscope technology, we show for the first time that a subpopulation of astrocytes in the adult mouse brain expresses Dagla, albeit at …

Anxiety, Stress, and Fear Response in Mice With Reduced Endocannabinoid Levels

2016

Abstract Background Disruption of the endocannabinoid system through pharmacological or genetic invalidation of cannabinoid CB 1 receptors has been linked to depression in humans and depression-like behaviors in mice. The two main endogenous cannabinoids, anandamide and 2-arachidonoyl glycerol (2-AG), are produced on demand from phospholipids. The pathways and enzymes involved in endocannabinoid biosynthesis thus play a major role in regulating the activity of this system. This study investigates the role of the main 2-AG producing enzyme diacylglycerol lipase α (DAGL-α). Methods We generated and used knockout mice lacking DAGL-α ( Dagla −/− ) to assess the behavioral consequences of reduce…

Neurotrophic and neuroprotective effects of muscle contraction

2016

Background: Physical activity has been shown to be associated with reduced risk of coronary heart disease but the same effect seems to be produced in neurological diseases. Objective: In this review, we focused on the interplay between physical activity and some neurological conditions (Stroke, dementia, epilepsy, headache, Parkinson’ s disease, amyotrophic lateral sclerosis, multiple sclerosis, insomnia, depression and anxiety) with the aim of describing the potential role of physical activity in the prevention of such diseases and the physiological mechanisms involved in these processes. Results: Despite a growing body of evidence which reveals that physical activity is able to reduce the…

Antiepileptogenic Effect of Subchronic Palmitoylethanolamide Treatment in a Mouse Model of Acute Epilepsy

2018

Research on the antiepileptic effects of (endo-)cannabinoids has remarkably progressed in the years following the discovery of fundamental role of the endocannabinoid (eCB) system in controlling neural excitability. Moreover, an increasing number of well-documented cases of epilepsy patients exhibiting multi-drug resistance report beneficial effects of cannabis use. Pre-clinical and clinical research has increasingly focused on the antiepileptic effectiveness of exogenous administration of cannabinoids and/or pharmacologically induced increase of eCBs such as anandamide (also known as arachidonoylethanolamide [AEA]). Concomitant research has uncovered the contribution of neuroinflammatory p…

Polymorphism rs1761667 in the CD36 Gene Is Associated to Changes in Fatty Acid Metabolism and Circulating Endocannabinoid Levels Distinctively in Nor…

2017

The multifunctional CD36 scavenger receptor facilitates fatty acid (FA) uptake and oxidation and it has been involved in the pathophysiology related to dysfunctional FA metabolism. The common variant in the CD36 gene, rs1761667 (A/G), whose allele A is characterized by a reduced protein expression, has been associated with taste sensitivity to and preference for fat. We therefore aimed at evaluating whether the CD36 polymorphism may influence fatty acid metabolism and endocannabinoid biosynthesis in normal weight (NW) and obese (OB) subjects. Red blood cell (RBC) fatty acid composition, and plasma endocannabinoid levels were determined. In NW subjects with AA genotype was found a marked red…