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CB2 microglia

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https://www.readbyqxmd.com/read/28899427/activation-of-dorsal-horn-cannabinoid-cb2-receptor-suppresses-the-expression-of-p2y12-and-p2y13-receptors-in-neuropathic-pain-rats
#1
Juan Niu, Dujuan Huang, Rui Zhou, MingXia Yue, Tao Xu, Junna Yang, Li He, Hong Tian, XiaoHong Liu, Junwei Zeng
BACKGROUND: More evidence suggests that dorsal spinal cord microglia is an important site contributing to CB2 receptor-mediated analgesia. The upregulation of P2Y12 and P2Y13 purinoceptors in spinal dorsal horn microglia is involved in the development of pain behavior caused by peripheral nerve injury. However, it is not known whether the expression of P2Y12 and P2Y13 receptors at spinal dorsal horn will be influenced after CB2 receptor activation in neuropathic pain rats. METHODS: Chronic constriction injury (CCI) and intrathecal ADPbetaS injection were performed in rats to induce neuropathic pain...
September 12, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28888955/distinct-roles-of-neuronal-and-microglial-cb2-cannabinoid-receptors-in-the-mouse-hippocampus
#2
Yong Li, Jimok Kim
The effects of cannabinoids are primarily mediated by type-1 cannabinoid receptors in the brain and type-2 cannabinoid receptors (CB2Rs) in the peripheral immune system. However, recent evidence demonstrates that CB2Rs are also expressed in the brain and implicated in neuropsychiatric effects. Diverse types of cells in various regions in the brain express CB2Rs but the cellular loci of CB2Rs that induce specific behavioral effects have not been determined. To manipulate CB2R expression in specific types of cells in the dorsal hippocampus of adult mice, we used Cre-dependent overexpression and CRISPR-Cas9 genome editing techniques in combination with adeno-associated viruses and transgenic mice...
September 6, 2017: Neuroscience
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
#3
Gemma Navarro, Dasiel Borroto-Escuela, Edgar Angelats, Íñigo Etayo, Irene Reyes-Resina, Marta Pulido-Salgado, Ana I Rodriguez-Perez, 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. Unlike CB1, CB2 receptors and CB1-CB2Hets were upregulated in activated microglia...
August 23, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28828401/abnormalities-in-dynamic-brain-activity-caused-by-mild-traumatic-brain-injury-are-partially-rescued-by-the-cannabinoid-type-2-receptor-inverse-agonist-smm-189
#4
Yu Liu, Samuel S McAfee, Natalie M Guley, Nobel Del Mar, Wei Bu, Scott A Heldt, Marcia G Honig, Bob M Moore, Anton Reiner, Detlef H Heck
Mild traumatic brain injury (mTBI) can cause severe long-term cognitive and emotional deficits, including impaired memory, depression, and persevering fear, but the neuropathological basis of these deficits is uncertain. As medial prefrontal cortex (mPFC) and hippocampus play important roles in memory and emotion, we used multi-site, multi-electrode recordings of oscillatory neuronal activity in local field potentials (LFPs) in awake, head-fixed mice to determine if the functioning of these regions was abnormal after mTBI, using a closed-skull focal cranial blast model...
July 2017: ENeuro
https://www.readbyqxmd.com/read/28551012/activation-of-cb2-receptor-system-restores-cognitive-capacity-and-hippocampal-sox2-expression-in-a-transgenic-mouse-model-of-alzheimer-s-disease
#5
Jiang Wu, Mark Hocevar, Joseph F Foss, Bihua Bie, Mohamed Naguib
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by neuroinflammation, extensive deposits of amyloid-β aggregates, and loss of memory and cognitive abilities. The brains of patients with AD show increased expression of cannabinoid receptor type 2 (CB2) receptors and glial markers. CB2 receptors act as a negative feedback regulator; when activated by a CB2 agonist, they can help limit the extent of the neuroinflammatory response and the subsequent development of neuronal damage in the central nervous system...
September 15, 2017: European Journal of Pharmacology
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
#6
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
#7
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/28253997/cb2-cannabinoid-receptors-modulate-hif-1%C3%AE-and-tim-3-expression-in-a-hypoxia-ischemia-mouse-model
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
https://www.readbyqxmd.com/read/27317300/upregulation-of-the-cannabinoid-cb2-receptor-in-environmental-and-viral-inflammation-driven-rat-models-of-parkinson-s-disease
#17
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
#18
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
#19
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
#20
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
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