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Endocannabinoid deficiency

M D Lange, T Daldrup, F Remmers, H J Szkudlarek, J Lesting, S Guggenhuber, S Ruehle, K Jüngling, T Seidenbecher, B Lutz, H C Pape
The brain circuits underlying behavioral fear have been extensively studied over the last decades. Although the vast majority of experimental studies assess fear as a transient state of apprehension in response to a discrete threat, such phasic states of fear can shift to a sustained anxious apprehension, particularly in face of diffuse cues with unpredictable environmental contingencies. Unpredictability, in turn, is considered an important variable contributing to anxiety disorders. The networks of the extended amygdala have been suggested keys to the control of phasic and sustained states of fear, although the underlying synaptic pathways and mechanisms remain poorly understood...
October 4, 2016: Molecular Psychiatry
Tamara L Doremus-Fitzwater, Linda P Spear
Adolescence is an evolutionarily conserved developmental period, with neural circuits and behaviors contributing to the detection, procurement, and receipt of rewards bearing similarity across species. Studies with laboratory animals suggest that adolescence is typified by a "reward-centric" phenotype-an increased sensitivity to rewards relative to adults. In contrast, adolescent rodents are reportedly less sensitive to the aversive properties of many drugs and naturally aversive stimuli. Alterations within the mesocorticolimbic dopamine and endocannabinoid systems likely contribute to an adolescent reward-sensitive, yet aversion-resistant, phenotype...
August 11, 2016: Neuroscience and Biobehavioral Reviews
David J Clarke, Jordyn Stuart, Iain S McGregor, Jonathon C Arnold
The endocannabinoid system is dysregulated in schizophrenia. Mice with heterozygous deletion of neuregulin 1 (Nrg1 HET mice) provide a well-characterised animal model of schizophrenia, and display enhanced sensitivity to stress and cannabinoids during adolescence. However, no study has yet determined whether these mice have altered brain endocannabinoid concentrations. Nrg1 application to hippocampal slices decreased 2-arachidonoylglycerol (2-AG) signalling and disrupted long-term depression, a form of synaptic plasticity critical to spatial learning...
January 4, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
V M Doenni, J M Gray, C M Song, S Patel, M N Hill, Q J Pittman
Early-life inflammation has been shown to exert profound effects on brain development and behavior, including altered emotional behavior, stress responsivity and neurochemical/neuropeptide receptor expression and function. The current study extends this research by examining the impact of inflammation, triggered with the bacterial compound lipopolysaccharide (LPS) on postnatal day (P) 14, on social behavior during adolescence. We investigated the role that the endocannabinoid (eCB) system plays in sociability after early-life LPS...
November 2016: Brain, Behavior, and Immunity
Miklós Sárvári, Imre Kalló, Erik Hrabovszky, Norbert Solymosi, Annie Rodolosse, Zsolt Liposits
Estradiol (E2) robustly activates transcription of a broad array of genes in the hippocampal formation of middle-aged ovariectomized rats via estrogen receptors (ERα, ERβ, and G protein-coupled ER). Selective ERβ agonists also influence hippocampal functions, although their downstream molecular targets and mechanisms are not known. In this study, we explored the effects of long-term treatment with ERβ agonist diarylpropionitrile (DPN, 0.05 mg/kg/day, sc.) on the hippocampal transcriptome in ovariectomized, middle-aged (13 month) rats...
2016: Frontiers in Cellular Neuroscience
Marta Celorrio, Diana Fernández-Suárez, Estefanía Rojo-Bustamante, Víctor Echeverry-Alzate, María J Ramírez, Cecilia J Hillard, José A López-Moreno, Rafael Maldonado, Julen Oyarzábal, Rafael Franco, María S Aymerich
Elements of the endocannabinoid system are strongly expressed in the basal ganglia where they suffer profound rearrangements after dopamine depletion. Modulation of the levels of the endocannabinoid 2-arachidonoyl-glycerol by inhibiting monoacylglycerol lipase alters glial phenotypes and provides neuroprotection in a mouse model of Parkinson's disease. In this study, we assessed whether inhibiting fatty acid amide hydrolase could also provide beneficial effects on the time course of this disease. The fatty acid amide hydrolase inhibitor, URB597, was administered chronically to mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and probenecid (MPTPp) over 5weeks...
October 2016: Brain, Behavior, and Immunity
Ki-Tae Suk, Ingmar Mederacke, Geum-Youn Gwak, Sung Won Cho, Adebowale Adeyemi, Richard Friedman, Robert F Schwabe
OBJECTIVE: The endocannabinoid system (ECS) exerts key roles in the development of liver fibrosis and fatty liver, two diseases that promote the development of hepatocellular carcinoma (HCC). Although cannabinoids exert potent antitumour effects in vitro, the contribution of the ECS to carcinogenesis in vivo remains elusive. DESIGN: Expression of key components of the ECS, including endocannanabinoids, endocannabinoid-degrading enzymes and endocannabinoid receptors, was determined in healthy liver and tumours...
October 2016: Gut
Matthew N Hill, Francis S Lee
No abstract text is available yet for this article.
May 15, 2016: Biological Psychiatry
Cristina Palomo-Garo, Yolanda Gómez-Gálvez, Concepción García, Javier Fernández-Ruiz
Most of cases of Parkinson's disease (PD) have a sporadic origin, with their causes mostly unknown, although overexposure to some environmental factors has been found to occur in some cases. Other forms of parkinsonism are the consequence of dominant or recessive mutations in specific genes, e.g. α-synuclein, parkin and, more recently, leucine-rich repeat kinase 2 (LRRK2), whose G2019S mutation represents the most prevalent form of late-onset, autosomal dominant familial PD. A transgenic mouse model expressing the G2019S mutation of LRRK2 is already available and apparently may represent a valuable experimental model for investigating PD pathogenesis and novel treatments...
August 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
S C Dyall, H K Mandhair, R E A Fincham, D M Kerr, M Roche, F Molina-Holgado
Emerging evidence suggests a complex interplay between the endocannabinoid system, omega-3 fatty acids and the immune system in the promotion of brain self-repair. However, it is unknown if all omega-3 fatty acids elicit similar effects on adult neurogenesis and if such effects are mediated or regulated by interactions with the endocannabinoid system. This study investigated the effects of DHA and EPA on neural stem cell (NSC) fate and the role of the endocannabinoid signalling pathways in these effects. EPA, but not DHA, significantly increased proliferation of NSCs compared to controls, an effect associated with enhanced levels of the endocannabinoid 2-arachidonylglycerol (2-AG) and p-p38 MAPK, effects attenuated by pre-treatment with CB1 (AM251) or CB2 (AM630) receptor antagonists...
August 2016: Neuropharmacology
Ian Burkovskiy, Juan Zhou, Christian Lehmann
OBJECTIVE: Severe CNS injury, such as stroke, traumatic brain injury, or spinal cord injury, is known to increase susceptibility to infections. The increased susceptibility to infection is due to an impaired immune response and is referred to as CIDS. The CB2 receptor on immune cells presents a potential therapeutic target in CIDS as activation of this receptor has been shown to be involved in immunosuppression. The main purpose of this study was to determine the impact of CB2 receptor inhibition on leukocyte activation within the microcirculation following endotoxin challenge in an experimental stroke model...
May 2016: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
G J Stephens
Cerebellar ataxias represent a spectrum of disorders which are, however, linked by common symptoms of motor incoordination and typically associated with deficiency in Purkinje cell firing activity and, often, degeneration. Cerebellar ataxias currently lack a curative agent. The endocannabinoid (eCB) system includes eCB compounds and their associated metabolic enzymes, together with cannabinoid receptors, predominantly the cannabinoid CB1 receptor (CB1 R) in the cerebellum; activation of this system in the cerebellar cortex is associated with deficits in motor coordination characteristic of ataxia, effects which can be prevented by CB1 R antagonists...
August 15, 2016: Journal of Physiology
Aurore Thomazeau, Clémentine Bosch-Bouju, Olivier Manzoni, Sophie Layé
Maternal n-3 polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid, is critical during perinatal brain development. How early postnatal n-3 PUFA deficiency impacts on hippocampal synaptic plasticity is mostly unknown. Here we compared activity-dependent plasticity at excitatory and inhibitory synapses in the CA1 region of the hippocampus in weaned pups whose mothers were fed with an n-3 PUFA-balanced or n-3 PUFA-deficient diet. Normally, endogenous cannabinoids (eCB) produced by the post-synapse dually control network activity by mediating the long-term depression of inhibitory inputs (iLTD) and positively gating NMDAR-dependent long-term potentiation (LTP) of excitatory inputs...
March 5, 2016: Cerebral Cortex
Katja Zschiebsch, Caroline Fischer, Geethanjali Pickert, Annett Häussler, Heinfried Radeke, Sabine Grösch, Nerea Ferreirós, Gerd Geisslinger, Ernst R Werner, Irmgard Tegeder
BACKGROUND AND AIMS: Guanosine triphosphate cyclohydrolase [GCH1] governs the production of the enzyme cofactor tetrahydrobiopterin [BH4] which is essential for biogenic amine synthesis, lipid metabolism via alkylglycerol monooxygenase [AGMO], and redox coupling of nitric oxide synthases [NOSs]. Inflammation-evoked unequal regulation of GCH1 and NOS or AGMO may cause redox stress and lipid imbalances. METHODS: The present study assessed potential therapeutic effects of rebalancing these systems with BH4 in experimental colitis in mice...
August 2016: Journal of Crohn's & Colitis
Leah Y Liu, Kristen Alexa, Mauricio Cortes, Stephanie Schatzman-Bone, Andrew J Kim, Bani Mukhopadhyay, Resat Cinar, George Kunos, Trista E North, Wolfram Goessling
Endocannabinoid (EC) signaling mediates psychotropic effects and regulates appetite. By contrast, potential roles in organ development and embryonic energy consumption remain unknown. Here, we demonstrate that genetic or chemical inhibition of cannabinoid receptor (Cnr) activity disrupts liver development and metabolic function in zebrafish (Danio rerio), impacting hepatic differentiation, but not endodermal specification: loss of cannabinoid receptor 1 (cnr1) and cnr2 activity leads to smaller livers with fewer hepatocytes, reduced liver-specific gene expression and proliferation...
February 15, 2016: Development
Sherry Shu-Jung Hu
Rimonabant is well recognized as a cannabinoid CB₁ receptor antagonist/inverse agonist. Rimonabant not only antagonizes the effects induced by exogenous cannabinoids and endocannabinoids at CB₁ receptors, it also exerts several pharmacological and behavioral effects independent of CB₁ receptor inactivation. For example, rimonabant can function as a low-potency mixed agonist/antagonist of the transient receptor potential vanilloid receptor 1 (TRPV1). Hence, it is important to explain the underlying mechanisms of the diverse physiological effects induced by rimonabant with caution...
February 29, 2016: Chinese Journal of Physiology
R B Frei, P Luschnig, G P Parzmair, M Peinhaupt, S Schranz, A Fauland, C E Wheelock, A Heinemann, E M Sturm
BACKGROUND: Accumulation of activated eosinophils in tissue is a hallmark of allergic inflammation. The endocannabinoid 2-arachidonoylglycerol (2-AG) has been proposed to elicit eosinophil migration in a CB2 receptor/Gi/o -dependent manner. However, it has been claimed recently that this process may also involve other mechanisms such as cytokine priming and the metabolism of 2-AG into eicosanoids. Here, we explored the direct contribution of specific CB2 receptor activation to human and mouse eosinophil effector function in vitro and in vivo...
July 2016: Allergy
A Adibfar, M Saleem, K L Lanctot, N Herrmann
Depression, the most common mood disorder, is a leading contributor to the global burden of disease affecting more than 120 million individuals worldwide. Various pathophysiological processes underlie depression; this complexity renders it difficult to identify clinically useful diagnostic and prognostic markers, as well as treatment options. The current state of knowledge driving the management and treatment of depression remains incomplete, which underscores the need for further insight into pathways relevant to depression...
2016: Current Molecular Medicine
V Rosato, L Abenavoli, A Federico, M Masarone, M Persico
AIMS: Alcohol is the most commonly used addictive substance and alcoholic liver disease (ALD) is a major cause of chronic liver disease worldwide, responsible for 47.9% of all liver chronic deaths. Despite ALD has a significant burden on the health, few therapeutic advances have been made in the last 40 years, particularly in the long-term management of these patients. METHODS: we searched in PubMed, Scopus, Google Scholar, and MEDLINE databases to identify relevant English language publications focused on long-term therapy of ALD...
February 2016: International Journal of Clinical Practice
Nemanja Vujic, Stefanie Schlager, Thomas O Eichmann, Corina T Madreiter-Sokolowski, Madeleine Goeritzer, Silvia Rainer, Silvia Schauer, Angelika Rosenberger, Albert Woelfler, Prakash Doddapattar, Robert Zimmermann, Gerald Hoefler, Achim Lass, Wolfgang F Graier, Branislav Radovic, Dagmar Kratky
BACKGROUND AND AIMS: Monoglyceride lipase (MGL) catalyzes the final step of lipolysis by degrading monoglyceride (MG) to glycerol and fatty acid. MGL also hydrolyzes and thereby deactivates 2-arachidonoyl glycerol (2-AG), the most abundant endocannabinoid in the mammalian system. 2-AG acts as full agonist on cannabinoid receptor type 1 (CB1R) and CB2R, which are mainly expressed in brain and immune cells, respectively. Thus, we speculated that in the absence of MGL, increased 2-AG concentrations mediate CB2R signaling in immune cells to modulate inflammatory responses, thereby affecting the development of atherosclerosis...
January 2016: Atherosclerosis
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