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Endocannabinoid deficiency

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https://www.readbyqxmd.com/read/29748627/deficient-endocannabinoid-signaling-in-the-central-amygdala-contributes-to-alcohol-dependence-related-anxiety-like-behavior-and-excessive-alcohol-intake
#1
Antonia Serrano, Francisco J Pavon, Matthew W Buczynski, Joel Schlosburg, Luis A Natividad, Ilham Y Polis, David G Stouffer, Eric P Zorrilla, Marisa Roberto, Benjamin F Cravatt, Rémi Martin-Fardon, Fernando Rodriguez de Fonseca, Loren H Parsons
Negative emotional states that are associated with excessive alcohol intake, particularly anxiety-like states, have been linked to opponent processes in the central nucleus of the amygdala (CeA), affecting stress-related transmitters and monoamines. This study extends these observations to include endocannabinoid signaling in alcohol-dependent animals. Rats and mice were exposed to chronic intermittent alcohol with vapor inhalation or liquid diet to induce dependence. In vivo microdialysis was used to estimate interstitial concentrations of endocannabinoids [N-arachidonoylethanolamine (anandamide; AEA) and 2-arachidonoylglycerol (2-AG)] and amino acids (glutamate and GABA) in rat CeA...
April 5, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29740328/emerging-role-of-endo-cannabinoids-in-migraine
#2
REVIEW
Pinja Leimuranta, Leonard Khiroug, Rashid Giniatullin
In this mini-review, we summarize recent discoveries and present new hypotheses on the role of cannabinoids in controlling trigeminal nociceptive system underlying migraine pain. Individual sections of this review cover key aspects of this topic, such as: (i) the current knowledge on the endocannabinoid system (ECS) with emphasis on expression of its components in migraine related structures; (ii) distinguishing peripheral from central site of action of cannabinoids, (iii) proposed mechanisms of migraine pain and control of nociceptive traffic by cannabinoids at the level of meninges and in brainstem, (iv) therapeutic targeting in migraine of monoacylglycerol lipase and fatty acid amide hydrolase, enzymes which control the level of endocannabinoids; (v) dual (possibly opposing) actions of cannabinoids via anti-nociceptive CB1 and CB2 and pro-nociceptive TRPV1 receptors...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29707693/catsper-a-unique-calcium-channel-of-the-sperm-flagellum
#3
Polina V Lishko, Nadja Mannowetz
To overcome egg protective vestments and ensure successful fertilization, mammalian spermatozoa switch symmetrical progressive motility to a powerful, whip-like flagellar motion, known as hyperactivation. The latter is triggered by a calcium influx through the sperm-specific, voltage-dependent, and alkalization-activated calcium channel of sperm - CatSper. The channel comprises nine subunits which together form a heteromeric complex. CatSper-deficient male mice and men with mutations in CatSper genes are infertile...
April 2018: Current Opinion in Physiology
https://www.readbyqxmd.com/read/29686301/endocannabinoids-in-caenorhabditis-elegans-are-essential-for-the-mobilization-of-cholesterol-from-internal-reserves
#4
Celina Galles, Gastón M Prez, Sider Penkov, Sebastian Boland, Exequiel O J Porta, Silvia G Altabe, Guillermo R Labadie, Ulrike Schmidt, Hans-Joachim Knölker, Teymuras V Kurzchalia, Diego de Mendoza
Proper cholesterol transport is crucial for the functionality of cells. In C. elegans, certain cholesterol derivatives called dafachronic acids (DAs) govern the entry into diapause. In their absence, worms form a developmentally arrested dauer larva. Thus, cholesterol transport to appropriate places for DA biosynthesis warrants the reproductive growth. Recently, we discovered a novel class of glycosphingolipids, PEGCs, required for cholesterol mobilization/transport from internal storage pools. Here, we identify other components involved in this process...
April 23, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29670176/activity-dependent-modulation-of-hippocampal-synaptic-plasticity-via-pirb-and-endocannabinoids
#5
Maja Djurisic, Barbara K Brott, Nay L Saw, Mehrdad Shamloo, Carla J Shatz
The threshold for Hebbian synaptic plasticity in the CNS is modulated by prior synaptic activity. At adult CA3-CA1 synapses, endocannabinoids play a role in this process, but how activity engages and maintains this retrograde signaling system is not well understood. Here we show that conditional deletion of Paired Immunoglobulin-like receptor B (PirB) from pyramidal neurons in adult mouse hippocampus results in deficient LTD at CA3-CA1 synapses over a range of stimulation frequencies, accompanied by an increase in LTP...
April 18, 2018: Molecular Psychiatry
https://www.readbyqxmd.com/read/29660628/transcriptional-abundance-of-type-1-endocannabinoid-receptor-cb1-and-fatty-acid-amide-hydrolase-faah-in-bull-spermatozoa-relationship-with-field-fertility
#6
Vimlesh Kumar, Arumugam Kumaresan, Pradeep Nag, Puneeth Kumar, Tirtha Kumar Datta, Rubina Kumari Baithalu, Tushar Kumar Mohanty
A highly sophisticated endogenous cannabinoid system (ECS) has been shown to play a crucial role in controlling sperm functions and fertility in men. In the present study, we report the differences in the expression level of components of ECS [type-1 endocannabinoid receptor (CB1) and fatty acid amide hydrolase (FAAH)] in spermatozoa from bulls with different field fertility ratings. Cryopreserved spermatozoa from crossbred cattle bulls (n = 40) were utilized for the study. The bulls were classified into high-, medium- and low-fertile bulls based on field conception rates...
April 8, 2018: Theriogenology
https://www.readbyqxmd.com/read/29570114/fatty-acid-binding-proteins-5-and-7-gene-deletion-increases-sucrose-consumption-and-diminishes-forced-swim-immobility-time
#7
John Hamilton, Christopher Koumas, Brendan H Clavin, Matthew Marion, Antonio Figueiredo, Steve Gonzalez, Joseph R O'Rourke, Dale Deutsch, Martin Kaczocha, Samir Haj-Dahmane, Panayotis K Thanos
Inhibition and genetic deletion of fatty acid-binding proteins (FABPs) 5 and 7 have been shown to increase the levels of the endocannabinoid anandamide as well as the related N-acylethanolamine's palmitoylethanolamide and oleoylethanolamide. This study examined the role of these FABPs on forced-swim (FS) behavior and on sucrose consumption in two experiments: (experiment 1) using wild-type (WT) mice treated with the FABP inhibitor SBFI26 or vehicle and (experiment 2) using WT and FABP5/7 deficient mice. Results from experiment 1 showed that acute treatment with SBFI26 did not have any effect on sucrose intake or FS behavior in mice...
March 21, 2018: Behavioural Pharmacology
https://www.readbyqxmd.com/read/29458998/role-of-striatal-direct-pathway-2-arachidonoylglycerol-signaling-in-sociability-and-repetitive-behavior
#8
Brian C Shonesy, Walker P Parrish, Hala K Haddad, Jason R Stephenson, Rita Báldi, Rebecca J Bluett, Christian R Marks, Samuel W Centanni, Oakleigh M Folkes, Keeley Spiess, Shana M Augustin, Ken Mackie, David M Lovinger, Danny G Winder, Sachin Patel, Roger J Colbran
BACKGROUND: Endocannabinoid signaling plays an important role in regulating synaptic transmission in the striatum, a brain region implicated as a central node of dysfunction in autism spectrum disorder. Deficits in signaling mediated by the endocannabinoid 2-arachidonoylglycerol (2-AG) have been reported in mouse models of autism spectrum disorder, but a causal role for striatal 2-AG deficiency in phenotypes relevant to autism spectrum disorder has not been explored. METHODS: Using conditional knockout mice, we examined the electrophysiological, biochemical, and behavioral effects of 2-AG deficiency by deleting its primary synthetic enzyme, diacylglycerol lipase α (DGLα), from dopamine D1 receptor-expressing or adenosine A2a receptor-expressing medium spiny neurons (MSNs) to determine the role of 2-AG signaling in striatal direct or indirect pathways, respectively...
December 28, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/29274505/age-related-regulation-of-bone-formation-by-the-sympathetic-cannabinoid-cb1-receptor
#9
Saif Deis, Raj Kamal Srivastava, Inigo Ruiz de Azua, Laura Bindila, Saja Baraghithy, Beat Lutz, Itai Bab, Joseph Tam
The endocannabinoid (eCB) system, including its receptors, ligands, and their metabolizing enzymes, plays an important role in bone physiology. Skeletal cannabinoid type 1 (CB1) receptor signaling transmits retrograde signals that restrain norepinephrine (NE) release, thus transiently stimulating bone formation following an acute challenge, suggesting a feedback circuit between sympathetic nerve terminals and osteoblasts. To assess the effect of chronic in vivo occurrence of this circuit, we characterized the skeletal phenotype of mice with a conditional deletion of the CB1 receptor in adrenergic/noradrenergic cells, including sympathetic nerves...
March 2018: Bone
https://www.readbyqxmd.com/read/29167401/acetaminophen-relieves-inflammatory-pain-through-cb-1-cannabinoid-receptors-in-the-rostral-ventromedial-medulla
#10
Pascal P Klinger-Gratz, William T Ralvenius, Elena Neumann, Ako Kato, Rita Nyilas, Zsolt Lele, István Katona, Hanns Ulrich Zeilhofer
Acetaminophen (paracetamol) is a widely used analgesic and antipyretic drug with only incompletely understood mechanisms of action. Previous work, using models of acute nociceptive pain, indicated that analgesia by acetaminophen involves an indirect activation of CB1 receptors by the acetaminophen metabolite and endocannabinoid reuptake inhibitor AM 404. However, the contribution of the cannabinoid system to antihyperalgesia against inflammatory pain, the main indication of acetaminophen, and the precise site of the relevant CB1 receptors have remained elusive...
January 10, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29145497/rare-genetic-variants-in-the-endocannabinoid-system-genes-cnr1-and-dagla-are-associated-with-neurological-phenotypes-in-humans
#11
Douglas R Smith, Christine M Stanley, Theodore Foss, Richard G Boles, Kevin McKernan
Rare genetic variants in the core endocannabinoid system genes CNR1, CNR2, DAGLA, MGLL and FAAH were identified in molecular testing data from 6,032 patients with a broad spectrum of neurological disorders. The variants were evaluated for association with phenotypes similar to those observed in the orthologous gene knockouts in mice. Heterozygous rare coding variants in CNR1, which encodes the type 1 cannabinoid receptor (CB1), were found to be significantly associated with pain sensitivity (especially migraine), sleep and memory disorders-alone or in combination with anxiety-compared to a set of controls without such CNR1 variants...
2017: PloS One
https://www.readbyqxmd.com/read/29068398/precision-nutrition-and-omega-3-polyunsaturated-fatty-acids-a-case-for-personalized-supplementation-approaches-for-the-prevention-and-management-of-human-diseases
#12
REVIEW
Floyd H Chilton, Rahul Dutta, Lindsay M Reynolds, Susan Sergeant, Rasika A Mathias, Michael C Seeds
BACKGROUND: Dietary essential omega-6 ( n -6) and omega-3 ( n -3) 18 carbon (18C-) polyunsaturated fatty acids (PUFA), linoleic acid (LA) and α-linolenic acid (ALA), can be converted (utilizing desaturase and elongase enzymes encoded by FADS and ELOVL genes) to biologically-active long chain (LC; >20)-PUFAs by numerous cells and tissues. These n -6 and n -3 LC-PUFAs and their metabolites (ex, eicosanoids and endocannabinoids) play critical signaling and structural roles in almost all physiologic and pathophysiologic processes...
October 25, 2017: Nutrients
https://www.readbyqxmd.com/read/29031713/peripheral-cannabinoid-1-receptor-blockade-restores-hypothalamic-leptin-signaling
#13
Joseph Tam, Gergő Szanda, Adi Drori, Ziyi Liu, Resat Cinar, Yoshihiro Kashiwaya, Marc L Reitman, George Kunos
OBJECTIVE: In visceral obesity, an overactive endocannabinoid/CB1 receptor (CB1 R) system promotes increased caloric intake and decreases energy expenditure, which are mitigated by global or peripheral CB1 R blockade. In mice with diet-induced obesity (DIO), inhibition of food intake by the peripherally restricted CB1 R antagonist JD5037 could be attributed to endogenous leptin due to the rapid reversal of hyperleptinemia that maintains leptin resistance, but the signaling pathway engaged by leptin has remained to be determined...
October 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28852269/cannabinoid-receptor-2-modulates-neutrophil-recruitment-in-a-murine-model-of-endotoxemia
#14
Theodore S Kapellos, Carlota Recio, David R Greaves, Asif J Iqbal
The endocannabinoid system consists of endogenous lipid mediators and cannabinoid receptors (CB) 1 and 2. It has previously been demonstrated that activation of the leukocyte-expressed CB2 has anti-inflammatory effects in vivo . Here, we report its role under baseline conditions and in a model of low-dose endotoxemia by comparing CB2 knockout to littermate control mice. CB2 -deficient mice displayed significantly more neutrophils and fewer monocytes in the bone marrow under steady state. In initial validation experiments, administration of 1 mg/kg LPS to male C57BL/6J mice was shown to transiently upregulate systemic proinflammatory mediators (peaked at 2 hours) and mobilise bone marrow neutrophils and monocytes into circulation...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28799288/neuroprotective-activity-of-cannabinoid-receptor-2-against-oxidative-stress-and-apoptosis-in-rat-pups-having-experimentally-induced-congenital-hypothyroidism
#15
Mehmet Eray Alcigir, Halef Okan Dogan, Sevil Atalay Vural, Fatma Meric Yilmaz
In this study, it was aimed to show the cannabinoid receptor-2 (CB2) role, which is a part of neuroprotective endocannabinoidal system, against increasing nitric oxide synthetase (iNOS, eNOS) levels and the apoptotic activity (caspase-3, caspase-9, and DNA in situ fragmentation) within the postnatal critical period in pups of pregnant rats with artificially induced maternal thyroid hormone (TH) deficiency. Each of the three groups established comprised one male and two female rats, and they were coupled. Their pups were used...
August 11, 2017: Developmental Neurobiology
https://www.readbyqxmd.com/read/28759733/protective-effect-of-rimonabant-a-canabinoid-receptor-1-antagonist-on-nonalcoholic-fatty-liver-disease-in-a-rat-model-through-modulation-of-the-hepatic-expression-of-activin-a-and-follistatin
#16
Noha I Hussien, Hanan I El-Kerdasy, Mohammad El-Tantawy Ibrahim
Non-alcoholic fatty liver disease (NAFLD) is a major cause of liver morbidity and mortality, and there is still no proven effective therapy. The endocannabinoid system plays an important role in various liver diseases. Activin A is a member of the transforming growth factor beta (TGF-β) superfamily and inhibits hepatocyte growth. Follistatin antagonizes the biological actions of activin A. This study was designed to investigate the effect of rimonabant (a potent cannabinoid receptor1 (CB1) antagonist) on NAFLD induced with a choline-deficient (CD) diet in rats, as well as to detect whether it can alter the hepatic expression of activin A and follistatin...
July 31, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28752643/combined-deficiency-of-the-cnr1-and-cnr2-receptors-protects-against-age-related-bone-loss-by-osteoclast-inhibition
#17
Antonia Sophocleous, Silvia Marino, Dilruba Kabir, Stuart H Ralston, Aymen I Idris
The endocannabinoid system plays a role in regulating bone mass and bone cell activity and inactivation of the type 1 (Cnr1) or type 2 (Cnr2) cannabinoid receptors influences peak bone mass and age-related bone loss. As the Cnr1 and Cnr2 receptors have limited homology and are activated by different ligands, we have evaluated the effects of combined deficiency of Cnr1 and 2 receptors (Cnr1/2(-/-) ) on bone development from birth to old age and studied ovariectomy induced bone loss in female mice. The Cnr1/2(-/-) mice had accelerated bone accrual at birth when compared with wild type littermates, and by 3 months of age, they had higher trabecular bone mass...
October 2017: Aging Cell
https://www.readbyqxmd.com/read/28745306/integrating-endocannabinoid-signaling-and-cannabinoids-into-the-biology-and-treatment-of-posttraumatic-stress-disorder
#18
Matthew N Hill, Patrizia Campolongo, Rachel Yehuda, Sachin Patel
Exposure to stress is an undeniable, but in most cases surmountable, part of life. However, in certain individuals, exposure to severe or cumulative stressors can lead to an array of pathological conditions including posttraumatic stress disorder (PTSD), characterized by debilitating trauma-related intrusive thoughts, avoidance behaviors, hyperarousal, as well as depressed mood and anxiety. In the context of the rapidly changing political and legal landscape surrounding use of cannabis products in the USA, there has been a surge of public and research interest in the role of cannabinoids in the regulation of stress-related biological processes and in their potential therapeutic application for stress-related psychopathology...
January 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28630250/amplification-of-mglu5-endocannabinoid-signaling-rescues-behavioral-and-synaptic-deficits-in-a-mouse-model-of-adolescent-and-adult-dietary-polyunsaturated-fatty-acid-imbalance
#19
Antonia Manduca, Anissa Bara, Thomas Larrieu, Olivier Lassalle, Corinne Joffre, Sophie Layé, Olivier J Manzoni
Energy-dense, yet nutritionally poor food is a high-risk factor for mental health disorders. This is of particular concern during adolescence, a period often associated with increased consumption of low nutritional content food and higher prevalence of mental health disorders. Indeed, there is an urgent need to understand the mechanisms linking unhealthy diet and mental disorders. Deficiency in n-3 polyunsaturated fatty acids (PUFAs) is a hallmark of poor nutrition and mood disorders. Here, we developed a mouse model of n-3 PUFA deficiency lasting from adolescence into adulthood...
July 19, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28515018/plasma-levels-of-the-endocannabinoid-anandamide-related-n-acylethanolamines-and-linoleic-acid-derived-oxylipins-in-patients-with-migraine
#20
Sandra Gouveia-Figueira, Kristina Goldin, Sanaz A Hashemian, Agneta Lindberg, Monica Persson, Malin L Nording, Katarina Laurell, Christopher J Fowler
There is evidence that patients with migraine have deficient levels of the endogenous cannabinoid receptor ligand anandamide (AEA). It is not known, however, if this is a localised or generalised phenomenon. In the present study, levels of AEA, related N-acylethanolamines (NAEs) and linoleic acid-derived oxylipins have been measured in the blood of 26 healthy women and 38 women with migraine (26 with aura, 12 without aura) who were matched for age and body-mass index. Blood samples were taken on two occasions: the first sample near the start of the menstrual cycle (when present) and the second approximately fourteen days later...
May 2017: Prostaglandins, Leukotrienes, and Essential Fatty Acids
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