Search results for "endocannabinoid"

Differential diurnal variations of anandamide and 2-arachidonoyl-glycerol levels in rat brain.

2004

The endogenous ligands of cannabinoid receptors, also known as endocannabinoids, have been implicated in many physiological and pathological processes of the central nervous system. Here we show that the levels of the two major endocannabinoids, anandamide and 2-arachidonoyl-glycerol (2-AG), in four areas of the rat brain, change dramatically between the light and dark phases of the day. While anandamide levels in the nucleus accumbens, pre-frontal cortex, striatum and hippocampus were significantly higher in the dark phase, the opposite was observed with 2-AG, whose levels were significantly higher during the light phase in all four regions. We found that the activity of the fatty acid ami…

Spinal Endocannabinoids and CB 1 Receptors Mediate C-Fiber–Induced Heterosynaptic Pain Sensitization

2009

Plastic Pain Perception Drugs and endocannabinoids acting on cannabinoid (CB) receptors have potential in the treatment of certain types of pain. In the spinal cord they are believed to suppress nociception, the perception of pain and noxious stimuli. Pernia-Andrade et al. (p. 760 ) now find that endocannabinoids, which are released in spinal cord by noxious stimulation, may promote rather than inhibit nociception by acting on CB1 receptors. Endocannabinoids not only depress transmission at excitatory synapses in the spinal cord, but also block the release of inhibitory neurotransmitters, thereby facilitating nociception.

Long‐term molecular differences between resilient and susceptible mice after a single traumatic exposure

2022

Post-traumatic stress disorder (PTSD) is a heterogeneous disorder induced by trauma, resulting in severe long-term impairments of an individual's mental health. PTSD does not develop in every individual and, thus, some individuals are more resilient. However, the underlying molecular mechanisms are poorly understood. Here, we aimed to elucidate these processes.We used a single-trauma PTSD model in mice to induce long-term maladaptive behaviours and profiled the mice 4 weeks after trauma into resilient or susceptible individuals. The classification of phenotype was based on individual responses in different behavioural experiments. We analysed microbiome, circulating endocannabinoids, and lo…

Plasma Parameters of the Endocannabinoid System Are Unaltered in Fibromyalgia.

2018

Cannabinoid receptor 1 modulates the autophagic flux independent of mTOR- and BECLIN1-complex

2013

Cannabinoid Receptor 1 (CB1) has been initially described as the receptor for Delta-9-Tetrahydrocannabinol in the central nervous system (CNS), mediating retrograde synaptic signaling of the endocannabinoid system. Beside its expression in various CNS regions, CB1 is ubiquituous in peripheral tissues, where it mediates, among other activities, the cell's energy homeostasis. We sought to examine the role of CB1 in the context of the evolutionarily conserved autophagic machinery, a main constituent of the regulation of the intracellular energy status. Manipulating CB1 by siRNA knockdown in mammalian cells caused an elevated autophagic flux, while the expression of autophagy-related genes rema…

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…

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…

Plasticity of mouse enteric synapses mediated through endocannabinoid and purinergic signaling

2012

The myenteric and submucosal plexuses of the enteric nervous system (ENS) exist as interconnected integrative nerve networks within the wall of the gastrointestinal (GI) tract. Activity of the ENS is responsible for the control of the digestive and protective functions of the gut.1 Synaptic transmission between enteric neurons propagates information from intrinsic afferent neurons to interneurons, and then from interneurons to motor neurons that control final effectors such as smooth muscle and the secretory epithelium. Acetylcholine (ACh) is the major excitatory neurotransmitter in the myenteric plexus, acting on nicotinic receptors at synapses between neurons and on muscarinic receptors a…

Direct suppression of CNS autoimmune inflammation via the cannabinoid receptor CB1 on neurons and CB2 on autoreactive T cells.

2007

The cannabinoid system is immunomodulatory and has been targeted as a treatment for the central nervous system (CNS) autoimmune disease multiple sclerosis. Using an animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), we investigated the role of the CB(1) and CB(2) cannabinoid receptors in regulating CNS autoimmunity. We found that CB(1) receptor expression by neurons, but not T cells, was required for cannabinoid-mediated EAE suppression. In contrast, CB(2) receptor expression by encephalitogenic T cells was critical for controlling inflammation associated with EAE. CB(2)-deficient T cells in the CNS during EAE exhibited reduced levels of apoptosis, a higher…

2021

Brain homeostasis is the dynamic equilibrium whereby physiological parameters are kept actively within a specific range. The homeostatic range is not fixed and may change throughout the individual's lifespan, or may be transiently modified in the presence of severe perturbations. The endocannabinoid system has emerged as a safeguard of homeostasis, e.g., it modulates neurotransmission and protects neurons from prolonged or excessively strong activation. We used genetically engineered mouse lines that lack the cannabinoid type-1 receptor (CB1) either in dorsal telencephalic glutamatergic or in forebrain GABAergic neurons to create new allostatic states, resulting from alterations in the exci…