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Endocannabinoid microglia

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https://www.readbyqxmd.com/read/29786066/repeated-social-defeat-induced-neuroinflammation-anxiety-like-behavior-and-resistance-to-fear-extinction-were-attenuated-by-the-cannabinoid-receptor-agonist-win55-212-2
#1
Sabrina Francesca Lisboa, Anzela Niraula, Leonardo Barbosa Resstel, Francisco Silveira Guimaraes, Jonathan P Godbout, John F Sheridan
Psychosocial stress contributes to the development of psychiatric disorders. Repeated social defeat (RSD) is a murine stressor that causes a release of inflammatory monocytes into circulation. Moreover, RSD-induced anxiety-like behavior is dependent on the recruitment of these monocytes to the brain. Activation of the endocannabinoid (ECB) system may modulate both neuroendocrine and inflammatory responses mediated by stress. Therefore, we hypothesized that a cannabinoid receptor agonist would attenuate RSD-induced inflammation, anxiety, and stress sensitization...
April 17, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29725299/octadecylpropyl-sulfamide-reduces-neurodegeneration-and-restores-the-memory-deficits-induced-by-hypoxia-ischemia-in-mice
#2
Elk Kossatz, Daniel Silva-Peña, Juan Suárez, Fernando R de Fonseca, Rafael Maldonado, Patricia Robledo
The PPAR-α agonist, oleoylethanolamide (OEA) has neuroprotective properties in stroke models. However, its rapid degradation represents a limitation for an effective therapeutic approach. In this study, we evaluated the effects of a stable OEA-modeled compound, octadecylpropyl sulfamide (SUL) on the cognitive, behavioral, cellular and molecular alterations associated with hypoxia-ischemia (HI) in mice. Mice subjected to HI were treated with the PPAR-α antagonist GW6471 (GW) (1 mg/kg) followed 15 min later by SUL (3 and 10 mg/kg)...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29579222/inhibition-of-fatty-acid-amide-hydrolase-by-pf-3845-alleviates-the-nitrergic-and-proinflammatory-response-in-rat-hippocampus-following-acute-stress
#3
Hsiao-Jou Cortina Chen, Jereme G Spiers, Conrad Sernia, Nickolas A Lavidis
Background: Long term exposure to stress has been demonstrated to cause neuroinflammation through a sustained overproduction of free radicals, including nitric oxide, via an increased inducible nitric oxide synthase (iNOS) activity. We have previously demonstrated that iNOS activity and mRNA are significantly upregulated in the rat hippocampus following just 4 hours of restraint stress. Similar to nitric oxide, endocannabinoids are synthesised on demand, with preclinical observations suggesting that cannabinoid receptor agonists and endocannabinoid enhancers inhibit nitrergic activity...
March 22, 2018: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29560022/paeoniflorin-exerts-neuroprotective-effects-by-modulating-the-m1-m2-subset-polarization-of-microglia-macrophages-in-the-hippocampal-ca1-region-of-vascular-dementia-rats-via-cannabinoid-receptor-2
#4
Xian-Qin Luo, Ao Li, Xue Yang, Xiao Xiao, Rong Hu, Tian-Wen Wang, Xiao-Yun Dou, Da-Jian Yang, Zhi Dong
Background: Cerebral hypoperfusion is a pivotal risk factor for vascular dementia (VD), for which effective therapy remains inadequate. Persistent inflammatory responses and excessive chemotaxis of microglia/macrophages in the brain may accelerate the progression of VD. Endocannabinoids are involved in neuronal protection against inflammation-induced neuronal injury. Cannabinoids acting at cannabinoid receptor 2 (CB2 R) can decrease inflammation. Based on the identification of paeoniflorin (PF) as a CB2 R agonist, we investigated the neuroprotective and microglia/macrophages M1 to M2 polarization promoting effects of PF in a permanent four-vessel occlusion rat model...
2018: Chinese Medicine
https://www.readbyqxmd.com/read/29484707/2-ag-limits-theiler-s-virus-induced-acute-neuroinflammation-by-modulating-microglia-and-promoting-mdscs
#5
Miriam Mecha, Ana Feliú, Isabel Machín, Cesar Cordero, Francisco Carrillo-Salinas, Leyre Mestre, Gloria Hernández-Torres, Silvia Ortega-Gutiérrez, María L López-Rodríguez, Fernando de Castro, Diego Clemente, Carmen Guaza
The innate immune response is mediated by primary immune modulators such as cytokines and chemokines that together with immune cells and resident glia orchestrate CNS immunity and inflammation. Growing evidence supports that the endocannabinoid 2-arachidonoylglycerol (2-AG) exerts protective actions in CNS injury models. Here, we used the acute phase of Theiler's virus induced demyelination disease (TMEV-IDD) as a model of acute neuroinflammation to investigate whether 2-AG modifies the brain innate immune responses to TMEV and CNS leukocyte trafficking...
February 27, 2018: Glia
https://www.readbyqxmd.com/read/29392440/cannabinoids-and-glial-cells-possible-mechanism-to-understand-schizophrenia
#6
REVIEW
Valéria de Almeida, Daniel Martins-de-Souza
Clinical and neurobiological findings have reported the involvement of endocannabinoid signaling in the pathophysiology of schizophrenia. This system modulates dopaminergic and glutamatergic neurotransmission that is associated with positive, negative, and cognitive symptoms of schizophrenia. Despite neurotransmitter impairments, increasing evidence points to a role of glial cells in schizophrenia pathobiology. Glial cells encompass three main groups: oligodendrocytes, microglia, and astrocytes. These cells promote several neurobiological functions, such as myelination of axons, metabolic and structural support, and immune response in the central nervous system...
February 1, 2018: European Archives of Psychiatry and Clinical Neuroscience
https://www.readbyqxmd.com/read/29352424/cannabinoid-cb1-and-cb2-receptors-and-monoacylglycerol-lipase-gene-expression-alterations-in-the-basal-ganglia-of-patients-with-parkinson-s-disease
#7
Francisco Navarrete, M Salud García-Gutiérrez, Auxiliadora Aracil-Fernández, José L Lanciego, Jorge Manzanares
Previous studies suggest that the endocannabinoid system plays an important role in the neuropathological basis of Parkinson's disease (PD). This study was designed to detect potential alterations in the cannabinoid receptors CB1 (CB1 r) and CB2 (A isoform, CB2A r), and in monoacylglycerol lipase (MAGL) gene expression in the substantia nigra (SN) and putamen (PUT) of patients with PD. Immunohistochemical studies were performed to identify precise CB2 r cellular localization in the SN of control and PD patients...
January 19, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/29310667/wwl70-protects-against-chronic-constriction-injury-induced-neuropathic-pain-in-mice-by-cannabinoid-receptor-independent-mechanisms
#8
Jie Wen, Melissa Jones, Mikiei Tanaka, Prabhuanand Selvaraj, Aviva J Symes, Brian Cox, Yumin Zhang
BACKGROUND: Targeting the endocannabinoid system has emerged as an effective strategy for the treatment of inflammatory and neurological diseases. Unlike the inhibition of the principal 2-arachidonyl glycerol (2-AG) hydrolytic enzyme monoacylglycerol lipase (MAGL), which leads to 2-AG overload and cannabinoid receptor desensitization, selective inhibition of the minor 2-AG hydrolytic enzyme alpha, beta-hydrolase domain 6 (ABHD6) can provide therapeutic benefits without producing cannabimimetic side effects...
January 8, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28843453/receptor-heteromer-mediated-regulation-of-endocannabinoid-signaling-in-activated-microglia-role-of-cb1-and-cb2-receptors-and-relevance-for-alzheimer-s-disease-and-levodopa-induced-dyskinesia
#9
Gemma Navarro, Dasiel Borroto-Escuela, Edgar Angelats, Íñigo Etayo, Irene Reyes-Resina, Marta Pulido-Salgado, Ana I Rodríguez-Pérez, Enric I Canela, Josep Saura, José Luis Lanciego, José Luis Labandeira-García, Carlos A Saura, Kjell Fuxe, Rafael Franco
Endocannabinoids are important regulators of neurotransmission and, acting on activated microglia, they are postulated as neuroprotective agents. Endocannabinoid action is mediated by CB1 and CB2 receptors, which may form heteromeric complexes (CB1-CB2Hets) with unknown function in microglia. We aimed at establishing the expression and signaling properties of cannabinoid receptors in resting and LPS/IFN-γ-activated microglia. In activated microglia mRNA transcripts increased (2 fold for CB1 and circa 20 fold for CB2), whereas receptor levels were similar for CB1 and markedly upregulated for CB2; CB1-CB2Hets were also upregulated...
January 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28826718/contrasting-effects-of-selective-magl-and-faah-inhibition-on-dopamine-depletion-and-gdnf-expression-in-a-chronic-mptp-mouse-model-of-parkinson-s-disease
#10
Noemi Pasquarelli, Christoph Porazik, Hanna Bayer, Eva Buck, Stefan Schildknecht, Patrick Weydt, Anke Witting, Boris Ferger
The modulation of the brain endocannabinoid system has been identified as an option to treat neurodegenerative diseases including Parkinson's disease (PD). Especially the elevation of endocannabinoid levels by inhibition of hydrolytic degradation represents a valuable approach. To evaluate whether monoacylglycerol lipase (MAGL) or fatty acid amide hydrolase (FAAH) inhibition could be beneficial for PD, we examined in parallel the therapeutic potential of the highly selective MAGL inhibitor KML29 elevating 2-arachidonoylglyerol (2-AG) levels and the highly selective FAAH inhibitor PF-3845 elevating anandamide (AEA) levels in a chronic methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid (MPTP/probenecid) mouse model of PD...
November 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28356120/in-vivo-tspo-and-cannabinoid-receptor-type-2-availability-early-in-post-stroke-neuroinflammation-in-rats-a-positron-emission-tomography-study
#11
Teruyo Hosoya, Dai Fukumoto, Takeharu Kakiuchi, Shingo Nishiyama, Shigeyuki Yamamoto, Hiroyuki Ohba, Hideo Tsukada, Takatoshi Ueki, Kohji Sato, Yasuomi Ouchi
BACKGROUND: Upregulated levels of 18-kDa translocator proteins (TSPO) and type 2 endocannabinoid receptors (CB2) are considered to reflect different aspects of microglia-related neuroinflammatory responses in the brain. Relative to the increase in the TSPO expression that occurs slightly later during neuroinflammation in a proinflammatory fashion, CB2 activation is considered to relate to the neuroprotective responses that occurs predominantly at an early stage of brain disorders. These findings, however, were deduced from studies with different animal samples under different experimental settings...
March 29, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28336953/palmitoylethanolamide-induces-microglia-changes-associated-with-increased-migration-and-phagocytic-activity-involvement-of-the-cb2-receptor
#12
F Guida, L Luongo, S Boccella, M E Giordano, R Romano, G Bellini, I Manzo, A Furiano, A Rizzo, R Imperatore, F A Iannotti, E D'Aniello, F Piscitelli, F Sca Rossi, L Cristino, V Di Marzo, V de Novellis, S Maione
The endogenous fatty acid amide palmitoylethanolamide (PEA) has been shown to exert anti-inflammatory actions mainly through inhibition of the release of pro-inflammatory molecules from mast cells, monocytes and macrophages. Indirect activation of the endocannabinoid (eCB) system is among the several mechanisms of action that have been proposed to underlie the different effects of PEA in vivo. In this study, we used cultured rat microglia and human macrophages to evaluate whether PEA affects eCB signaling. PEA was found to increase CB2 mRNA and protein expression through peroxisome proliferator-activated receptor-α (PPAR-α) activation...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28292183/n-docosahexaenoyl-dopamine-an-endocannabinoid-like-conjugate-of-dopamine-and-the-n-3-fatty-acid-docosahexaenoic-acid-attenuates-lipopolysaccharide-induced-activation-of-microglia-and-macrophages-via-cox-2
#13
Ya Wang, Pierluigi Plastina, Jean-Paul Vincken, Renate Jansen, Michiel Balvers, Jean Paul Ten Klooster, Harry Gruppen, Renger Witkamp, Jocelijn Meijerink
Several studies indicate that the n-3 long-chain polyunsaturated fatty acid docosahexaenoic acid (DHA) contributes to an attenuated inflammatory status in the development of neurodegenerative disorders, such as Alzheimer's and Parkinson's disease. To explain these effects, different mechanisms are being proposed, including those involving endocannabinoids and related signaling molecules. Many of these compounds belong to the fatty acid amides, conjugates of fatty acids with biogenic amines. Conjugates of DHA with ethanolamine or serotonin have previously been shown to possess anti-inflammatory and potentially neuroprotective properties...
March 15, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28115138/endocannabinoid-2-arachidonoylglycerol-protects-inflammatory-insults-from-sulfur-dioxide-inhalation-via-cannabinoid-receptors-in-the-brain
#14
Ben Li, Minjun Chen, Lin Guo, Yang Yun, Guangke Li, Nan Sang
Sulfur dioxide (SO2 ) pollution in the atmospheric environment causes brain inflammatory insult and inflammatory-related microvasculature dysfunction. However, there are currently no effective medications targeting the harmful outcomes from chemical inhalation. Endocannabinoids (eCBs) are involved in neuronal protection against inflammation-induced neuronal injury. The 2-arachidonoylglycerol (2-AG), the most abundant eCBs and a full agonist for cannabinoid receptors (CB1 and CB2), is also capable of suppressing proinflammatory stimuli and improving microvasculature dysfunction...
January 2017: Journal of Environmental Sciences (China)
https://www.readbyqxmd.com/read/28104279/effect-of-inhibition-of-fatty-acid-amide-hydrolase-on-mptp-induced-dopaminergic-neuronal-damage
#15
J M Viveros-Paredes, R E Gonzalez-Castañeda, A Escalante-Castañeda, A R Tejeda-Martínez, F Castañeda-Achutiguí, M E Flores-Soto
INTRODUCTION: Parkinson's disease (PD) is a neurodegenerative disorder characterised by balance problems, muscle rigidity, and slow movement due to low dopamine levels and loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). The endocannabinoid system is known to modulate the nigrostriatal pathway through endogenous ligands such as anandamide (AEA), which is hydrolysed by fatty acid amide hydrolase (FAAH). The purpose of this study was to increase AEA levels using FAAH inhibitor URB597 to evaluate the modulatory effect of AEA on dopaminergic neuronal death induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)...
January 16, 2017: Neurología: Publicación Oficial de la Sociedad Española de Neurología
https://www.readbyqxmd.com/read/28086912/wwl70-attenuates-pge2-production-derived-from-2-arachidonoylglycerol-in-microglia-by-abhd6-independent-mechanism
#16
Mikiei Tanaka, Sean Moran, Jie Wen, Kwame Affram, Tinghua Chen, Aviva J Symes, Yumin Zhang
BACKGROUND: α/β-Hydrolase domain 6 (ABHD6) is one of the major enzymes for endocannabinoid 2-arachidonoylglycerol (2-AG) hydrolysis in microglia cells. Our recent studies have shown that a selective ABHD6 inhibitor WWL70 has anti-inflammatory and neuroprotective effects in animal models of traumatic brain injury and multiple sclerosis. However, the role of ABHD6 in the neuroinflammatory response and the mechanisms by which WWL70 suppresses inflammation has not yet been elucidated in reactive microglia...
January 10, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27531971/cannabinoid-type-2-cb2-receptors-activation-protects-against-oxidative-stress-and-neuroinflammation-associated-dopaminergic-neurodegeneration-in-rotenone-model-of-parkinson-s-disease
#17
Hayate Javed, Sheikh Azimullah, M Emdadul Haque, Shreesh K Ojha
The cannabinoid type two receptors (CB2), an important component of the endocannabinoid system, have recently emerged as neuromodulators and therapeutic targets for neurodegenerative diseases including Parkinson's disease (PD). The downregulation of CB2 receptors has been reported in the brains of PD patients. Therefore, both the activation and the upregulation of the CB2 receptors are believed to protect against the neurodegenerative changes in PD. In the present study, we investigated the CB2 receptor-mediated neuroprotective effect of β-caryophyllene (BCP), a naturally occurring CB2 receptor agonist, in, a clinically relevant, rotenone (ROT)-induced animal model of PD...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/27512365/synthesis-and-biological-evaluation-of-thiophene-based-cannabinoid-receptor-type-2-radiotracers-for-pet-imaging
#18
Ahmed Haider, Adrienne Müller Herde, Roger Slavik, Markus Weber, Claudia Mugnaini, Alessia Ligresti, Roger Schibli, Linjing Mu, Simon Mensah Ametamey
Over the past two decades, our understanding of the endocannabinoid system has greatly improved due to the wealth of results obtained from exploratory studies. Currently, two cannabinoid receptor subtypes have been well-characterized. The cannabinoid receptor type 1 (CB1) is widely expressed in the central nervous system, while the levels of the cannabinoid receptor type 2 (CB2) in the brain and spinal cord of healthy individuals are relatively low. However, recent studies demonstrated a CB2 upregulation on activated microglia upon neuroinflammation, an indicator of neurodegeneration...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/27425766/expression-of-the-endocannabinoid-receptor-1-in-human-stroke-an-autoptic-study
#19
Paola Caruso, Marcello Naccarato, Valentina Faoro, Danae Pracella, Marta Borando, Isabella Dotti, Nadia Koscica, Giorgio Stanta, Gilberto Pizzolato, Paolo Manganotti
OBJECTIVE: Stroke is one of the leading causes of disability and death in the world. The endocannabinoid (eCB) system is upregulated in several neurological diseases including stroke. A previous animal study demonstrated an increased expression of the endocannabinoid receptor 1 (CB1R) in the penumbra area surrounding the ischemic core, suggesting a crucial role in inflammation/reperfusion after stroke. Regarding the localization of CB1/CB2 receptors, animal studies showed that cortical neurons, activated microglia, and astroglia are involved...
September 2016: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/27373505/microglia-activation-states-and-cannabinoid-system-therapeutic-implications
#20
REVIEW
M Mecha, F J Carrillo-Salinas, A Feliú, L Mestre, C Guaza
Microglial cells are recognized as the brain's intrinsic immune cells, mediating actions that range from the protection against harmful conditions that modify CNS homeostasis, to the control of proliferation and differentiation of neurons and their synaptic pruning. To perform these functions, microglia adopts different activation states, the so-called phenotypes that depending on the local environment involve them in neuroinflammation, tissue repair and even the resolution of the inflammatory process. There is accumulating evidence indicating that cannabinoids (CBs) might serve as a promising tool to modify the outcome of inflammation, especially by influencing microglial activity...
October 2016: Pharmacology & Therapeutics
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