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Endocannabinoid system

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https://www.readbyqxmd.com/read/29227996/generation-and-phenotypic-characterisation-of-a-cytochrome-p450-4x1-knockout-mouse
#1
Himanshu Kharkwal, Farhat Batool, Frank Koentgen, David R Bell, David A Kendall, Francis J P Ebling, Ian R Duce
Cytochrome P450 4x1 (Cyp4x1) is expressed at very high levels in the brain but the function of this protein is unknown. It has been hypothesised to regulate metabolism of fatty acids and to affect the activity of endocannabinoid signalling systems, which are known to influence appetite and energy metabolism. The objective of the present investigation was to determine the impact of Cyp4x1 on body weight and energy metabolism by developing a line of transgenic Cyp4x1-knock out mice. Mice were developed with a global knock-out of the gene; the full-length RNA was undetectable, and mice were viable and fertile...
2017: PloS One
https://www.readbyqxmd.com/read/29223163/neuroprotective-properties-of-endocannabinoids-n-arachidonoyl-dopamine-and-n-docosahexaenoyl-dopamine-examined-in-neuronal-precursors-derived-from-human-pluripotent-stem-cells
#2
E V Novosadova, E L Arsenyeva, E S Manuilova, L G Khaspekov, M Yu Bobrov, V V Bezuglov, S N Illarioshkin, I A Grivennikov
Neuroprotective properties of endocannabinoids N-arachidonoyl dopamine (NADA) and N-docosahexaenoyl dopamine (DHDA) were examined in neuronal precursor cells differentiated from human induced pluripotent stem cells and subjected to oxidative stress. Both compounds exerted neuroprotective activity, which was enhanced by elevating the concentration of the endocannabinoids within the 0.1-10 µM range. However, both agents at 10 µM concentration showed a marked toxic effect resulting in death of ~30% of the cells...
November 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/29222605/the-endocannabinoid-system-in-cardiovascular-function-novel-insights-and-clinical-implications
#3
REVIEW
Salvador Sierra, Natasha Luquin, Judith Navarro-Otano
RATIONALE: Cardiovascular disease is now recognized as the number one cause of death in the world, and the size of the population at risk continues to increase rapidly. The dysregulation of the endocannabinoid (eCB) system plays a central role in a wide variety of conditions including cardiovascular disorders. Cannabinoid receptors, their endogenous ligands, as well as enzymes conferring their synthesis and degradation, exhibit overlapping distributions in the cardiovascular system. Furthermore, the pharmacological manipulation of the eCB system has effects on blood pressure, cardiac contractility, and endothelial vasomotor control...
December 8, 2017: Clinical Autonomic Research: Official Journal of the Clinical Autonomic Research Society
https://www.readbyqxmd.com/read/29219634/using-molecular-imaging-to-understand-early-schizophrenia-related-psychosis-neurochemistry-a-review-of-human-studies
#4
Christin Schifani, Sina Hafizi, Tania Da Silva, Jeremy Joseph Watts, M Saad Khan, Romina Mizrahi
Schizophrenia is a chronic psychiatric disorder generally preceded by a so-called prodromal phase, which is characterized by attenuated psychotic symptoms. Advances in clinical research have enabled prospective identification of those individuals who are at clinical high risk (CHR) for psychosis, with the power to predict psychosis onset within the near future. Changes in several brain neurochemical systems and molecular mechanisms are implicated in the pathophysiology of schizophrenia and the psychosis spectrum, including the dopaminergic, γ-aminobutyric acid (GABA)-ergic, glutamatergic, endocannabinoid, and immunologic (i...
December 8, 2017: International Review of Psychiatry
https://www.readbyqxmd.com/read/29218000/synapse-specific-regulation-revealed-at-single-synapses-is-concealed-when-recording-multiple-synapses
#5
Justin Lines, Ana Covelo, Ricardo Gómez, Lan Liu, Alfonso Araque
Synaptic transmission and its activity-dependent modulation, known as synaptic plasticity, are fundamental processes in nervous system function. Neurons may receive thousands of synaptic contacts, but synaptic regulation may occur only at individual or discrete subsets of synapses, which may have important consequences on the spatial extension of the modulation of synaptic information. Moreover, while several electrophysiological methods are used to assess synaptic transmission at different levels of observation, i...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29216450/endocannabinoid-actions-on-cortical-terminals-orchestrate-local-modulation-of-dopamine-release-in-the-nucleus-accumbens
#6
Yolanda Mateo, Kari A Johnson, Dan P Covey, Brady K Atwood, Hui-Ling Wang, Shiliang Zhang, Iness Gildish, Roger Cachope, Luigi Bellocchio, Manuel Guzmán, Marisela Morales, Joseph F Cheer, David M Lovinger
Dopamine (DA) transmission mediates numerous aspects of behavior. Although DA release is strongly linked to firing of DA neurons, recent developments indicate the importance of presynaptic modulation at striatal dopaminergic terminals. The endocannabinoid (eCB) system regulates DA release and is a canonical gatekeeper of goal-directed behavior. Here we report that extracellular DA increases induced by selective optogenetic activation of cholinergic neurons in the nucleus accumbens (NAc) are inhibited by CB1 agonists and eCBs...
December 6, 2017: Neuron
https://www.readbyqxmd.com/read/29203303/interactive-effects-of-morphine-and-nicotine-on-memory-function-depend-on-the-central-amygdala-cannabinoid-cb1-receptor-function-in-rats
#7
Fatemeh Tirgar, Ameneh Rezayof, Sakineh Alijanpour, Nima Yazdanbakhsh
The present study investigated the possible involvement of the central amygdala (CeA) cannabinoid receptors type-1 (CB1Rs) in the interactive effects of morphine and nicotine on memory formation in a passive avoidance learning task. Our results showed that systemic administration of morphine (3 and 6mg/kg, s.c.) immediately after training phase impaired memory consolidation and induced amnesia. Administration of nicotine (0.3 and 0.6mg/kg, s.c.) before testing phase significantly restored morphine-induced amnesia, suggesting a cross state-dependent learning between morphine and nicotine...
December 1, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29198512/understanding-the-role-of-serotonin-in-female-hypoactive-sexual-desire-disorder-and-treatment-options
#8
REVIEW
Harry A Croft
BACKGROUND: The neurobiology of sexual response is driven in part by dopamine and serotonin-the former modulating excitatory pathways and the latter regulating inhibitory pathways. Neurobiological underpinnings of hypoactive sexual desire disorder (HSDD) are seemingly related to overactive serotonin activity that results in underactive dopamine activity. As such, pharmacologic agents that decrease serotonin, increase dopamine, or some combination thereof, have therapeutic potential for HSDD...
December 2017: Journal of Sexual Medicine
https://www.readbyqxmd.com/read/29197803/redox-system-and-phospholipid-metabolism-in-the-kidney-of-hypertensive-rats-after-faah-inhibitor-urb597-administration
#9
Michał Biernacki, Ewa Ambrożewicz, Agnieszka Gęgotek, Marek Toczek, Katarzyna Bielawska, Elżbieta Skrzydlewska
Primary and secondary hypertension is associated with kidney redox imbalance resulting in enhanced reactive oxygen species (ROS) and enzymes dependent phospholipid metabolism. The fatty acid amide hydrolase inhibitor, URB597, modulates the levels of endocannabinoids, particularly of anandamide, which is responsible for controlling blood pressure and regulating redox balance. Therefore, this study aimed to compare the effects of chronic URB597 administration to spontaneously hypertensive rats (SHR) and rats with secondary hypertension (DOCA-salt rats) on the kidney metabolism associated with the redox and endocannabinoid systems...
November 27, 2017: Redox Biology
https://www.readbyqxmd.com/read/29196970/endocannabinoid-hydrolases-in-avian-hd11-macrophages-identified-by-chemoproteomics-inactivation-by-small-molecule-inhibitors-and-pathogen-induced-downregulation-of-their-activity
#10
Jung Hwa Lee, Xiang Hou, Evangel Kummari, Abdolsamad Borazjani, Mariola J Edelmann, Matthew K Ross
The endocannabinoids (eCBs) are endogenous arachidonoyl-containing lipid mediators with important roles in host defense. Macrophages are first-line defenders of the innate immune system and biosynthesize large amounts of eCBs when activated. The cellular levels of eCBs are controlled by the activities of their biosynthetic enzymes and catabolic enzymes, which include members of the serine hydrolase (SH) superfamily. The physiologic activity of SHs can be assessed in a class-specific way using chemoproteomic activity-based protein profiling (ABPP) methods...
December 1, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29192125/endocannabinoid-specific-impairment-in-synaptic-plasticity-in-striatum-of-huntington-s-disease-mouse-model
#11
Marja D Sepers, Amy Smith-Dijak, Jeff LeDue, Karolina Kolodziejczyk, Ken Mackie, Lynn A Raymond
Huntington's disease (HD) is an inherited neurodegenerative disease affecting predominantly striatum and cortex that results in motor and cognitive disorders. Prior to a motor phenotype, animal models of HD show aberrant cortical-striatal glutamate signaling. Here, we tested synaptic plasticity of cortical excitatory synapses onto striatal spiny projection neurons (SPNs) early in the YAC128 mouse model of HD. High frequency stimulation-induced long-term depression, mediated by the endocannabinoid anandamide and cannabinoid receptor 1 (CB1), was significantly attenuated in male and female YAC128 SPNs...
November 30, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29186065/binge-alcohol-exposure-transiently-changes-the-endocannabinoid-system-a-potential-target-to-prevent-alcohol-induced-neurodegeneration
#12
Daniel J Liput, James R Pauly, Audra L Stinchcomb, Kimberly Nixon
Excessive alcohol consumption leads to neurodegeneration, which contributes to cognitive decline that is associated with alcohol use disorders (AUDs). The endocannabinoid system has been implicated in the development of AUDs, but little is known about how the neurotoxic effects of alcohol impact the endocannabinoid system. Therefore, the current study investigated the effects of neurotoxic, binge-like alcohol exposure on components of the endocannabinoid system and related N-acylethanolamines (NAEs), and then evaluated the efficacy of fatty acid amide hydrolase (FAAH) inhibition on attenuating alcohol-induced neurodegeneration...
November 29, 2017: Brain Sciences
https://www.readbyqxmd.com/read/29176975/targeting-cannabinoid-signaling-in-the-immune-system-high-ly-exciting-questions-possibilities-and-challenges
#13
REVIEW
Attila Oláh, Zoltán Szekanecz, Tamás Bíró
It is well known that certain active ingredients of the plants of Cannabis genus, i.e., the "phytocannabinoids" [pCBs; e.g., (-)-trans-Δ9-tetrahydrocannabinol (THC), (-)-cannabidiol, etc.] can influence a wide array of biological processes, and the human body is able to produce endogenous analogs of these substances ["endocannabinoids" (eCB), e.g., arachidonoylethanolamine (anandamide, AEA), 2-arachidonoylglycerol (2-AG), etc.]. These ligands, together with multiple receptors (e.g., CB1 and CB2 cannabinoid receptors, etc...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29169961/the-cannabinoid-transporter-inhibitor-omdm-2-reduces-social-interaction-further-evidence-for-transporter-mediated-endocannabinoid-release
#14
Alexandre Seillier, Andrea Giuffrida
Experimental evidence suggests that the transport of endocannabinoids might work bi-directionally. Accordingly, it is possible that pharmacological blockade of the latter affects not only the re-uptake, but also the release of endocannabinoids, thus preventing them from stimulating CB1 receptors. We used biochemical, pharmacological, and behavioral approaches to investigate the effects of the transporter inhibitor OMDM-2 on social interaction, a behavioral assay that requires activation of CB1 receptors. The underlying mechanisms of OMDM-2 were compared with those of the Fatty Acid Amide Hydrolase (FAAH) inhibitor URB597...
November 21, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29167401/acetaminophen-relieves-inflammatory-pain-through-cb1-cannabinoid-receptors-in-the-rostral-ventromedial-medulla
#15
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 re-uptake inhibitor AM 404. However, the contribution of the cannabinoid system to anti-hyperalgesia against inflammatory pain, the main indication of acetaminophen, and the precise site of the relevant CB1 receptors have remained elusive...
November 22, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29165386/alterations-in-rat-accumbens-endocannabinoid-and-gaba-content-during-fentanyl-treatment-the-role-of-ghrelin
#16
Magdalena Sustkova-Fiserova, Chrysostomos Charalambous, Tereza Havlickova, Marek Lapka, Pavel Jerabek, Nina Puskina, Kamila Syslova
The opioid-induced rise of extracellular dopamine, endocannabinoid anandamide and γ-aminobutyric acid (GABA) concentrations triggered by opioids in the nucleus accumbens shell (NACSh) most likely participate in opioid reward. We have previously demonstrated that systemic administration of ghrelin antagonist (JMV2959) significantly decreased morphine-induced dopamine and anandamide (N-arachidonoylethanolamine, AEA) increase in the NACSh. Fentanyl is considered as a µ-receptor-selective agonist. The aim of this study was to test whether JMV2959, a growth hormone secretagogue receptor (GHS-R1A) antagonist, can influence the fentanyl-induced effects on anandamide, 2-arachidonoylglycerol (2-AG) and GABA in the NACSh and specify the involvement of GHS-R1A located in the ventral tegmental area (VTA) and nucleus accumbens (NAC)...
November 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29164003/the-endocannabinoid-system-in-pain-and-inflammation-its-relevance-to-rheumatic-disease
#17
REVIEW
Nicola Barrie, Nicholas Manolios
Pain is the most common manifestation of both acute and chronic inflammation that often challenges patients with rheumatic disease. Simply, we attribute this to local joint changes of pH in joints, the formation of radicals, enhanced joint pressure, or cytokine release acting on local nerves to produce pain. However, there is a more complex interplay of interactions between cytokines, mediators of inflammation, and ion channels that influence the final immune response and our perception of pain. Endocannabinoids, a group of less well-known endogenous bioactive lipids, have such manifold immunomodulatory effects able to influence both inflammation and pain...
September 2017: European Journal of Rheumatology
https://www.readbyqxmd.com/read/29156899/modulating-the-endocannabinoid-pathway-as-treatment-for-peripheral-neuropathic-pain-a-selected-review-of-preclinical-studies
#18
Shannon O'Hearn, Patrick Diaz, Bo Angela Wan, Carlo DeAngelis, Nicholas Lao, Leila Malek, Edward Chow, Alexia Blake
Chemotherapy-induced neuropathic pain is a distressing and commonly occurring side effect of many commonly used chemotherapeutic agents, which in some cases may prevent cancer patients from being able to complete their treatment. Cannabinoid based therapies have the potential to manage or even prevent pain associated with this syndrome. Pre-clinical animal studies that investigate the modulation of the endocannabinoid system (endogenous cannabinoid pathway) are being conducted to better understand the mechanisms behind this phenomenon...
August 31, 2017: Annals of Palliative Medicine
https://www.readbyqxmd.com/read/29151103/immunoregulatory-role-of-cannabinoids-during-infectious-disease
#19
Rosalía Hernández-Cervantes, Mónica Méndez-Díaz, Óscar Prospéro-García, Jorge Morales-Montor
Although the endocannabinoid system (ECS) is involved in the regulation of several physiological processes, including sleep and the immune response, its role during infections has not been fully studied. It is well known that the use of this drug increases susceptibility to infections because of the impact on the modulation of the immune system. Concerning the medicinal or recreational use of marijuana, its influence on the course of an infection, whether this has been caused by bacteria, viruses, parasites, and to a lesser degree, fungi, has been reported...
November 18, 2017: Neuroimmunomodulation
https://www.readbyqxmd.com/read/29151076/modulation-of-the-endocannabinoid-system-by-the-fatty-acid-amide-hydrolase-monoacylglycerol-and-diacylglycerol-lipase-inhibitors-as-an-attractive-target-for-secretory-diarrhoea-therapy
#20
A Wasilewski, A Misicka, M Sacharczuk, J Fichna
Secretory diarrhoea is a leading cause of mortality and morbidity worldwide. Our aim was to characterize the effect of inhibition of selected enzymes involved in the synthesis or degradation of endocannabinoids on electrolyte equilibrium in the mouse colonic tissue. The aim of this study was to evaluate the effects of PF-3845, JZL-184 and RHC-80267, as inhibitors of fatty acid amide hydrolase (FAAH), monoacylglycerol (MAGL) and diacylglycerol lipase (DAGL), respectively on epithelial ion transport in isolated mouse colon stimulated by forskolin (FSK), veratridine (VER) and bethanechol (BET)...
August 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
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