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https://www.readbyqxmd.com/read/28253997/cb2-cannabinoid-receptors-modulate-hif-1%C3%AE-and-tim-3-expression-in-a-hypoxia-ischemia-mouse-model
#1
Elk Kossatz, Rafael Maldonado, Patricia Robledo
The role of CB2 cannabinoid receptors (CB2R) in global brain lesions induced by hypoxia-ischemia (HI) insult is still unresolved. The aim of this study was to evaluate the involvement of CB2R in the behavioural and biochemical underpinnings related to brain damage induced by HI in adult mice, and the mechanisms involved. CB2R knockout (KO) mice and wild-type littermates (WT) underwent permanent ligation of the left common carotid artery and hypoxia. Behavioural measurements in the rotarod, beam walking, object recognition, open field, and Irwin tests were carried out 24h, 72h and 7 days...
December 2016: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28115138/endocannabinoid-2-arachidonoylglycerol-protects-inflammatory-insults-from-sulfur-dioxide-inhalation-via-cannabinoid-receptors-in-the-brain
#2
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/27766068/mild-traumatic-brain-injury-produces-neuron-loss-that-can-be-rescued-by-modulating-microglial-activation-using-a-cb2-receptor-inverse-agonist
#3
Wei Bu, Huiling Ren, Yunping Deng, Nobel Del Mar, Natalie M Guley, Bob M Moore, Marcia G Honig, Anton Reiner
We have previously reported that mild TBI created by focal left-side cranial blast in mice produces widespread axonal injury, microglial activation, and a variety of functional deficits. We have also shown that these functional deficits are reduced by targeting microglia through their cannabinoid type-2 (CB2) receptors using 2-week daily administration of the CB2 inverse agonist SMM-189. CB2 inverse agonists stabilize the G-protein coupled CB2 receptor in an inactive conformation, leading to increased phosphorylation and nuclear translocation of the cAMP response element binding protein (CREB), and thus bias activated microglia from a pro-inflammatory M1 to a pro-healing M2 state...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/27717112/activation-of-cannabinoid-receptor-2-attenuates-mechanical-allodynia-and-neuroinflammatory-responses-in-a-chronic-post-ischemic-pain-model-of-complex-regional-pain-syndrome-type-i-in-rats
#4
Jijun Xu, Yuying Tang, Mian Xie, Bihua Bie, Jiang Wu, Hui Yang, Joseph F Foss, Bin Yang, Richard W Rosenquist, Mohamed Naguib
Complex regional pain syndrome type 1 (CRPS-I) remains one of the most clinically challenging neuropathic pain syndromes and its mechanism has not been fully characterized. Cannabinoid receptor 2 (CB2) has emerged as a promising target for treating different neuropathic pain syndromes. In neuropathic pain models, activated microglia expressing CB2 receptors are seen in the spinal cord. Chemokine fractalkine receptor (CX3CR1) plays a substantial role in microglial activation and neuroinflammation. We hypothesized that a CB2 agonist could modulate neuroinflammation and neuropathic pain in an ischemia model of CRPS by regulating CB2 and CX3CR1 signaling...
December 2016: European Journal of Neuroscience
https://www.readbyqxmd.com/read/27534533/cb2-receptor-activation-prevents-glial-derived-neurotoxic-mediator-production-bbb-leakage-and-peripheral-immune-cell-infiltration-and-rescues-dopamine-neurons-in-the-mptp-model-of-parkinson-s-disease
#5
Young C Chung, Won-Ho Shin, Jeong Y Baek, Eun J Cho, Hyung H Baik, Sang R Kim, So-Yoon Won, Byung K Jin
The cannabinoid (CB2) receptor type 2 has been proposed to prevent the degeneration of dopamine neurons in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. However, the mechanisms underlying CB2 receptor-mediated neuroprotection in MPTP mice have not been elucidated. The mechanisms underlying CB2 receptor-mediated neuroprotection of dopamine neurons in the substantia nigra (SN) were evaluated in the MPTP mouse model of Parkinson's disease (PD) by immunohistochemical staining (tyrosine hydroxylase, macrophage Ag complex-1, glial fibrillary acidic protein, myeloperoxidase (MPO), and CD3 and CD68), real-time PCR and a fluorescein isothiocyanate-labeled albumin assay...
2016: Experimental & Molecular Medicine
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
#6
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
#7
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
#8
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
#9
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
https://www.readbyqxmd.com/read/27317300/upregulation-of-the-cannabinoid-cb2-receptor-in-environmental-and-viral-inflammation-driven-rat-models-of-parkinson-s-disease
#10
Ruth M Concannon, Bright N Okine, David P Finn, Eilís Dowd
In recent years, it has become evident that Parkinson's disease is associated with a self-sustaining cycle of neuroinflammation and neurodegeneration, with dying neurons activating microglia, which, once activated, can release several factors that kill further neurons. One emerging pharmacological target that has the potential to break this cycle is the microglial CB2 receptor which, when activated, can suppress microglial activity and reduce their neurotoxicity. However, very little is known about CB2 receptor expression in animal models of Parkinson's disease which is essential for valid preclinical assessment of the anti-Parkinsonian efficacy of drugs targeting the CB2 receptor...
September 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27303261/cb2-cannabinoid-receptor-as-potential-target-against-alzheimer-s-disease
#11
REVIEW
Ester Aso, Isidro Ferrer
The CB2 receptor is one of the components of the endogenous cannabinoid system, a complex network of signaling molecules and receptors involved in the homeostatic control of several physiological functions. Accumulated evidence suggests a role for CB2 receptors in Alzheimer's disease (AD) and indicates their potential as a therapeutic target against this neurodegenerative disease. Levels of CB2 receptors are significantly increased in post-mortem AD brains, mainly in microglia surrounding senile plaques, and their expression levels correlate with the amounts of Aβ42 and β-amyloid plaque deposition...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/26884647/cannabinoid-cb2-receptor-mediates-nicotine-induced-anti-inflammation-in-n9-microglial-cells-exposed-to-%C3%AE-amyloid-via-protein-kinase-c
#12
Ji Jia, Jie Peng, Zhaoju Li, Youping Wu, Qunlin Wu, Weifeng Tu, Mingchun Wu
BACKGROUND: Reducing β amyloid- (Aβ-) induced microglial activation is considered to be effective in treating Alzheimer's disease (AD). Nicotine attenuates Aβ-induced microglial activation; the mechanism, however, is still elusive. Microglia could be activated into classic activated state (M1 state) or alternative activated state (M2 state); the former is cytotoxic and the latter is neurotrophic. In this investigation, we hypothesized that nicotine attenuates Aβ-induced microglial activation by shifting microglial M1 to M2 state, and cannabinoid CB2 receptor and protein kinase C mediate the process...
2016: Mediators of Inflammation
https://www.readbyqxmd.com/read/26824325/up-regulation-of-immunomodulatory-effects-of-mouse-bone-marrow-derived-mesenchymal-stem-cells-by-tetrahydrocannabinol-pre-treatment-involving-cannabinoid-receptor-cb2
#13
Junran Xie, Dongju Xiao, Yun Xu, Jinning Zhao, Li Jiang, Xuming Hu, Yaping Zhang, Lina Yu
Chronic pain is commonly and closely correlated with inflammation. Both cannabinoid signaling and mesenchymal stem cells (MSCs) have been demonstrated to reduce inflammatory pain. Although cannabinoid signaling is essential for mesenchymal stem cell survival and differentiation, little is known about its role in modulatory effect of MSCs on inflammation and pain sensitivity. Here we showed that mouse bone-marrow derived MSCs (BM-MSCs) expressed both cannabinoid receptor type 1 and 2 (CB1 and CB2). CB2 expression level in BM-MSCs increased with their maturation...
February 9, 2016: Oncotarget
https://www.readbyqxmd.com/read/26819091/characterization-of-a-novel-adult-murine-immortalized-microglial-cell-line-and-its-activation-by-amyloid-beta
#14
Ryan C McCarthy, Dah-Yuu Lu, Ahmed Alkhateeb, Andrew M Gardeck, Chih-Hao Lee, Marianne Wessling-Resnick
BACKGROUND: Alzheimer's disease is associated with amyloid-beta (Aβ)-induced microglia activation. This pro-inflammatory response promotes neuronal damage, and therapies are sought to limit microglial activation. Screening efforts to develop new pharmacological inhibitors require a robust in vitro cell system. Current models lack significant responses to Aβ, and their use in examining age-related neurodegenerative diseases is questionable. For example, the commonly used BV-2 microglial line was derived from embryonic mononuclear cells and its activation by various stimuli is limited...
January 27, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/26515747/neuronal-expression-of-cb2-cannabinoid-receptor-mrnas-in-the-mouse-hippocampus
#15
Y Li, J Kim
In the brain, CB1 cannabinoid receptors primarily mediate the effects of cannabinoids, but CB2 cannabinoid receptors (CB2Rs) have recently been discovered in the nervous system and also implicated in neuromodulatory roles. To understand the mechanisms of CB2R functions in the brain, it is essential to localize CB2Rs, but the types of cells expressing CB2Rs have been controversial. Unequivocal localization of CB2Rs in the brain has been impeded in part by the low expression levels of CB2Rs and poor specificity of detection methods...
December 17, 2015: Neuroscience
https://www.readbyqxmd.com/read/26499171/cortical-neuroinflammation-contributes-to-long-term-cognitive-dysfunctions-following-adolescent-delta-9-tetrahydrocannabinol-treatment-in-female-rats
#16
Erica Zamberletti, Marina Gabaglio, Pamela Prini, Tiziana Rubino, Daniela Parolaro
Over 180 million people consume cannabis globally. Cannabis use peaks during adolescence with a trend for continued consumption by adults. Notably, several studies have shown that long-term and heavy cannabis use during adolescence can impair brain maturation and predispose to neurodevelopmental disorders, although the neurobiological mechanisms underlying this association remain largely unknown. In this study, we evaluated whether, in female rats, chronic administration of increasing doses of the psychotropic plant-derived cannabis constituent, delta-9-tetrahydrocannabinol (THC), during adolescence (PND 35-45) could affect microglia function in the long-term...
December 2015: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/26406232/expression-analysis-of-cb2-gfp-bac-transgenic-mice
#17
Anne-Caroline Schmöle, Ramona Lundt, Benjamin Gennequin, Hanna Schrage, Eva Beins, Alexandra Krämer, Till Zimmer, Andreas Limmer, Andreas Zimmer, David-Marian Otte
The endocannabinoid system (ECS) is a retrograde messenger system, consisting of lipid signaling molecules that bind to at least two G-protein-coupled receptors, Cannabinoid receptor 1 and 2 (CB1 and 2). As CB2 is primarily expressed on immune cells such as B cells, T cells, macrophages, dendritic cells, and microglia, it is of great interest how CB2 contributes to immune cell development and function in health and disease. Here, understanding the mechanisms of CB2 involvement in immune-cell function as well as the trafficking and regulation of CB2 expressing cells are crucial issues...
2015: PloS One
https://www.readbyqxmd.com/read/26196013/preclinical-evaluation-of-smm-189-a-cannabinoid-receptor-2-specific-inverse-agonist
#18
Chaela Presley, Ammaar Abidi, Satyendra Suryawanshi, Suni Mustafa, Bernd Meibohm, Bob M Moore
Cannabinoid receptor 2 agonists and inverse agonists are emerging as new therapeutic options for a spectrum of autoimmune-related disease. Of particular interest, is the ability of CB2 ligands to regulate microglia function in neurodegenerative diseases and traumatic brain injury. We have previously reported the receptor affinity of 3',5'-dichloro-2,6-dihydroxy-biphenyl-4-yl)-phenyl-methanone (SMM-189) and the characterization of the beneficial effects of SMM-189 in the mouse model of mild traumatic brain injury...
August 2015: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/26189763/activation-of-cb2-receptor-is-required-for-the-therapeutic-effect-of-abhd6-inhibition-in-experimental-autoimmune-encephalomyelitis
#19
Jie Wen, Rachel Ribeiro, Mikiei Tanaka, Yumin Zhang
Alpha/beta-hydrolase domain 6 (ABHD6) is a novel 2-arachidonoylglycerol (2-AG) hydrolytic enzyme, that can fine-tune the endocannabinoid signaling in the central nervous system. Recently we and others have demonstrated the protective effect of ABHD6 inhibition in the animal models of traumatic brain injury and epileptic seizures. In this study, we investigated the role of targeting ABHD6 in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Post-symptom treatment with an ABHD6 inhibitor WWL70 increased the brain levels of 2-AG and ameliorated the clinical signs of EAE, T cells infiltration, microglia activation and the expression of activated leukocyte cell adhesion molecules...
December 2015: Neuropharmacology
https://www.readbyqxmd.com/read/26090232/anandamide-acting-via-cb2-receptors-alleviates-lps-induced-neuroinflammation-in-rat-primary-microglial-cultures
#20
Natalia Malek, Katarzyna Popiolek-Barczyk, Joanna Mika, Barbara Przewlocka, Katarzyna Starowicz
Microglial activation is a polarized process divided into potentially neuroprotective phenotype M2 and neurotoxic phenotype M1, predominant during chronic neuroinflammation. Endocannabinoid system provides an attractive target to control the balance between microglial phenotypes. Anandamide as an immune modulator in the central nervous system acts via not only cannabinoid receptors (CB1 and CB2) but also other targets (e.g., GPR18/GPR55). We studied the effect of anandamide on lipopolysaccharide-induced changes in rat primary microglial cultures...
2015: Neural Plasticity
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