Search results for "endocannabinoid"

2021

White adipose tissue (WAT) possesses the endocannabinoid system (ECS) machinery and produces the two major endocannabinoids (ECs), arachidonoylethanolamide (AEA) and 2-arachidonoylglycerol (2-AG). Accumulating evidence indicates that WAT cannabinoid 1 receptors (CB1R) are involved in the regulation of fat storage, tissue remodeling and secretory functions but their role in controlling lipid mobilization is unclear. In the present study, we used different strategies to acutely increase ECS activity in WAT and tested the consequences on glycerol production as a marker of lipolysis. Treating lean mice or rat WAT explants with JLZ195, which inhibits ECs degrading enzymes, induced an increase in…

Impaired border zone formation and adverse remodeling after reperfused myocardial infarction in cannabinoid CB2 receptor deficient mice.

2014

Abstract Aims Reperfusion of myocardial infarction is associated with inflammatory reaction and subsequent myocardial remodeling with a rapid scar formation in mice. The cannabinoid receptor CB2 has been associated with cardioprotection and regulation of macrophage function. We investigated its role in remodeling of reperfused infarction. Main methods One hour LAD-occlusion was followed by reperfusion over 6 h and 1, 3 and 7 days in wild-type C57/BL6J (WT) and CB2 receptor-deficient (Cnr2 −/− ) mice (n = 8/group). Hearts were processed for functional, morphological and mRNA/protein analysis, and tissue concentration of endocannabinoids was determined using liquid chromatography-multiple rea…

The CB1 cannabinoid receptor mediates excitotoxicity-induced neural progenitor proliferation and neurogenesis.

2007

Endocannabinoids are lipid signaling mediators that exert an important neuromodulatory role and confer neuroprotection in several types of brain injury. Excitotoxicity and stroke can induce neural progenitor (NP) proliferation and differentiation as an attempt of neuroregeneration after damage. Here we investigated the mechanism of hippocampal progenitor cell engagement upon excitotoxicity induced by kainic acid administration and the putative involvement of the CB1 cannabinoid receptor in this process. Adult NPs express kainate receptors that mediate proliferation and neurosphere generation in vitro via CB1 cannabinoid receptors. Similarly, in vivo studies showed that excitotoxicity-induce…

The identification of peroxisome proliferator-activated receptor alpha-independent effects of oleoylethanolamide on intestinal transit in mice

2009

Oleoylethanolamide (OEA) is an endogenous lipid produced in the intestine that mediates satiety by activation of peroxisome proliferator-activated receptor alpha (PPARalpha). OEA inhibits gastric emptying and intestinal motility, but the mechanism of action remains to be determined. We investigated whether OEA inhibits intestinal motility by activation of PPARalpha. PPARalpha immunoreactivity was examined in whole mount preparations of mouse gastrointestinal (GI) tract. The effect of OEA on motility was assessed in wildtype, PPARalpha, cannabinoid CB(1) receptor and CB(2) receptor gene-deficient mice and in a model of accelerated GI transit. In addition, the effect of OEA on motility was as…

Endocannabinoid anandamide mediates hypoxic pulmonary vasoconstriction

2013

Endocannabinoids are important regulators of organ homeostasis. Although their role in systemic vasculature has been extensively studied, their impact on pulmonary vessels remains less clear. Herein, we show that the endocannabinoid anandamide (AEA) is a key mediator of hypoxic pulmonary vasoconstriction (HPV) via fatty acid amide hydrolase (FAAH)-dependent metabolites. This is underscored by the prominent vasoconstrictive effect of AEA on pulmonary arteries and strongly reduced HPV in FAAH(-/-) mice and wild-type mice upon pharmacological treatment with FAAH inhibitor URB597. In addition, mass spectrometry measurements revealed a clear increase of AEA and the FAAH-dependent metabolite arac…

Corticotropin-Releasing Hormone-Mediated Induction of Intracellular Signaling Pathways and Brain-Derived Neurotrophic Factor Expression Is Inhibited …

2005

CRH receptor (CRHR) 1 and the cannabinoid receptor 1 (CB1) are both G protein-coupled receptors. Activation of CRHR1 leadstoincreasesincAMPproductionandphosphorylationof the transcription factor cAMP response element-binding protein (CREB). In contrast, CB1 is negatively coupled to the cAMP signaling cascade. In this study, we analyzed a putative interaction between these two systems focusing on the regulation of the expression of brain-derived neurotrophic factor (BDNF), a CREB-regulated gene. In situ hybridization revealed coexpression of CRHR1 and CB1 receptors in the granular layer of the cerebellum. Therefore, we analyzed the effects of CRH and the CB1 agonist WIN-55,212-2 on BDNF expr…

Effect of Acetaldehyde Intoxication and Withdrawal on NPY Expression: Focus on Endocannabinoidergic System Involvement

2014

Acetaldehyde (ACD), the first alcohol metabolite, plays a pivotal role in the rewarding, motivational and addictive properties of the parental compound. Many studies have investigated the role of ACD in mediating neurochemical and behavioral effects induced by alcohol administration, but very little is known about the modulation of neuropeptide systems following ACD intoxication and withdrawal. Indeed the neuropeptide Y (NPY) system is altered during alcohol withdrawal in key regions for cerebrocortical excitability and neuroplasticity. The primary goal of this research was to investigate the effects of ACD intoxication and withdrawal by recording rat behavior and by measuring neuropeptide …

The Role of the Amygdala in the Extinction of Conditioned Fear

2006

The amygdala has long been known to play a central role in the acquisition and expression of fear. More recently, convergent evidence has implicated the amygdala in the extinction of fear as well. In rodents, some of this evidence comes from the infusion of drugs directly into the amygdala and, in particular, into the basolateral complex of the amygdala, during or after extinction learning. In vivo electrophysiology has identified cellular correlates of extinction learning and memory in the lateral nucleus of that structure. Human imaging experiments also indicate that amygdaloid activity correlates with extinction training. In addition, some studies have directly identified changes in mole…

Mitochondrial cannabinoid receptors gate corticosterone impact on novel object recognition

2023

: Corticosteroid-mediated stress responses require the activation of complex brain circuits involving mitochondrial activity, but the underlying cellular and molecular mechanisms are scantly known. The endocannabinoid system is implicated in stress coping, and it can directly regulate brain mitochondrial functions via type 1 cannabinoid (CB1) receptors associated with mitochondrial membranes (mtCB1). In this study, we show that the impairing effect of corticosterone in the novel object recognition (NOR) task in mice requires mtCB1 receptors and the regulation of mitochondrial calcium levels in neurons. Different brain circuits are modulated by this mechanism to mediate the impact of cortico…