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Endocannabinoid microglia

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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
#1
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
#2
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
#3
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
#4
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
#5
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/27266665/ethanol-downregulates-n-acyl-phosphatidylethanolamine-phospholipase-d-expression-in-bv2-microglial-cells-via-epigenetic-mechanisms
#6
Fernando Correa, Andrea De Laurentiis, Ana María Franchi
Excessive ethanol drinking has deleterious effects on the brain. However, the effects of alcohol on microglia, the main mediator of the brain's innate immune response remain poorly understood. On the other hand, the endocannabinoid system plays a fundamental role in regulating microglial reactivity and function. Here we studied the effects of acute ethanol exposure to murine BV2 microglial cells on N-acyl phosphatidylethanolamine-phospholipase D (NAPE-PLD), a major synthesizing enzyme of anandamide and other N-acylethanolamines...
September 5, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/26779719/a-chemical-proteomic-atlas-of-brain-serine-hydrolases-identifies-cell-type-specific-pathways-regulating-neuroinflammation
#7
Andreu Viader, Daisuke Ogasawara, Christopher M Joslyn, Manuel Sanchez-Alavez, Simone Mori, William Nguyen, Bruno Conti, Benjamin F Cravatt
Metabolic specialization among major brain cell types is central to nervous system function and determined in large part by the cellular distribution of enzymes. Serine hydrolases are a diverse enzyme class that plays fundamental roles in CNS metabolism and signaling. Here, we perform an activity-based proteomic analysis of primary mouse neurons, astrocytes, and microglia to furnish a global portrait of the cellular anatomy of serine hydrolases in the brain. We uncover compelling evidence for the cellular compartmentalization of key chemical transmission pathways, including the functional segregation of endocannabinoid (eCB) biosynthetic enzymes diacylglycerol lipase-alpha (DAGLα) and -beta (DAGLβ) to neurons and microglia, respectively...
2016: ELife
https://www.readbyqxmd.com/read/26517721/non-selective-cannabinoid-receptor-antagonists-hinokiresinols-reduce-infiltration-of-microglia-macrophages-into-ischemic-brain-lesions-in-rat-via-modulating-2-arachidonolyglycerol-induced-migration-and-mitochondrial-activity
#8
Angela M A Anthony Jalin, Maheswari Rajasekaran, Paul L Prather, Jin Sun Kwon, Veeraswamy Gajulapati, Yongseok Choi, Chunsook Kim, Kisoo Pahk, Chung Ju, Won-Ki Kim
Growing evidence suggests that therapeutic strategies to modulate the post-ischemic inflammatory responses are promising approaches to improve stroke outcome. Although the endocannabinoid system has been emerged as an endogenous therapeutic target to regulate inflammation after stroke insult, the downstream mechanisms and their potentials for therapeutic intervention remain controversial. Here we identified trans- and cis-hinokiresinols as novel non-selective antagonists for two G-protein-coupled cannabinoid receptors, cannabinoid receptor type 1 and type 2...
2015: PloS One
https://www.readbyqxmd.com/read/26408160/genetic-manipulation-of-the-endocannabinoid-system
#9
REVIEW
Andreas Zimmer
The physiological and pathophysiological functions of the endocannabinoid system have been studied extensively using transgenic and targeted knockout mouse models. The first gene deletions of the cannabinoid CB(1) receptor were described in the late 1990s, soon followed by CB(2) and FAAH mutations in early 2000. These mouse models helped to elucidate the fundamental role of endocannabinoids as retrograde transmitters in the CNS and in the discovery of many unexpected endocannabinoid functions, for example, in the skin, bone and liver...
2015: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/26406232/expression-analysis-of-cb2-gfp-bac-transgenic-mice
#10
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/26189763/activation-of-cb2-receptor-is-required-for-the-therapeutic-effect-of-abhd6-inhibition-in-experimental-autoimmune-encephalomyelitis
#11
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
#12
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
https://www.readbyqxmd.com/read/26086345/endocannabinoids-drive-the-acquisition-of-an-alternative-phenotype-in-microglia
#13
M Mecha, A Feliú, F J Carrillo-Salinas, A Rueda-Zubiaurre, S Ortega-Gutiérrez, R García de Sola, C Guaza
The ability of microglia to acquire diverse states of activation, or phenotypes, reflects different features that are determinant for their contribution to homeostasis in the adult CNS, and their activity in neuroinflammation, repair or immunomodulation. Despite the widely reported immunomodulatory effects of cannabinoids in both the peripheral immune system and the CNS, less is known about how the endocannabinoid signaling system (eCBSS) influence the microglial phenotype. The general aim of the present study was to investigate the role of endocannabinoids in microglia polarization by using microglia cell cultures...
October 2015: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/25963415/cannabinoid-receptor-2-attenuates-microglial-accumulation-and-brain-injury-following-germinal-matrix-hemorrhage-via-erk-dephosphorylation-in-vivo-and-in-vitro
#14
Jun Tang, Yihao Tao, Liang Tan, Liming Yang, Yin Niu, Qianwei Chen, Yunfeng Yang, Hua Feng, Zhi Chen, Gang Zhu
Microglia accumulation plays detrimental roles in the pathology of germinal matrix hemorrhage (GMH) in the immature preterm brain. However, the underlying mechanisms remain poorly defined. Here, we investigated the effects of a cannabinoid receptor 2 (CB2R) agonist on microglia proliferation and the possible involvement of the mitogen-activated protein kinase (MAPK) family pathway in a collagenase-induced GMH rat model and in thrombin-induced rat microglia cells. We demonstrated that activation of CB2R played a key role in attenuating brain edema, neuronal degeneration, microglial accumulation and the phosphorylated extracellular signal-regulated kinase (p-ERK) protein level 24 h following GMH...
August 2015: Neuropharmacology
https://www.readbyqxmd.com/read/25927213/monoacylglycerol-lipase-inhibitor-jzl184-reduces-neuroinflammatory-response-in-apde9-mice-and-in-adult-mouse-glial-cells
#15
Rea Pihlaja, Jatta Takkinen, Olli Eskola, Jenni Vasara, Francisco R López-Picón, Merja Haaparanta-Solin, Juha O Rinne
BACKGROUND: Recently, the role of monoacylglycerol lipase (MAGL) as the principal regulator of simultaneous prostaglandin synthesis and endocannabinoid receptor activation in the CNS was demonstrated. To expand upon previously published research in the field, we observed the effect of the MAGL inhibitor JZL184 during the early-stage proinflammatory response and formation of beta-amyloid (Aβ) in the Alzheimer's disease mouse model APdE9. We also investigated its effects in proinflammatory agent - induced astrocytes and microglia isolated from adult mice...
2015: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/25870539/pharmacological-blockade-of-the-fatty-acid-amide-hydrolase-faah-alters-neural-proliferation-apoptosis-and-gliosis-in-the-rat-hippocampus-hypothalamus-and-striatum-in-a-negative-energy-context
#16
Patricia Rivera, Laura Bindila, Antoni Pastor, Margarita Pérez-Martín, Francisco J Pavón, Antonia Serrano, Rafael de la Torre, Beat Lutz, Fernando Rodríguez de Fonseca, Juan Suárez
Endocannabinoids participate in the control of neurogenesis, neural cell death and gliosis. The pharmacological effect of the fatty acid amide hydrolase (FAAH) inhibitor URB597, which limits the endocannabinoid degradation, was investigated in the present study. Cell proliferation (phospho-H3(+) or BrdU(+) cells) of the main adult neurogenic zones as well as apoptosis (cleaved caspase-3(+)), astroglia (GFAP(+)), and microglia (Iba1(+) cells) were analyzed in the hippocampus, hypothalamus and striatum of rats intraperitoneally treated with URB597 (0...
2015: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/25568329/active-endocannabinoids-are-secreted-on-extracellular-membrane-vesicles
#17
Martina Gabrielli, Natalia Battista, Loredana Riganti, Ilaria Prada, Flavia Antonucci, Laura Cantone, Michela Matteoli, Mauro Maccarrone, Claudia Verderio
Endocannabinoids primarily influence neuronal synaptic communication within the nervous system. To exert their function, endocannabinoids need to travel across the intercellular space. However, how hydrophobic endocannabinoids cross cell membranes and move extracellularly remains an unresolved problem. Here, we show that endocannabinoids are secreted through extracellular membrane vesicles produced by microglial cells. We demonstrate that microglial extracellular vesicles carry on their surface N-arachidonoylethanolamine (AEA), which is able to stimulate type-1 cannabinoid receptors (CB1), and inhibit presynaptic transmission, in target GABAergic neurons...
February 2015: EMBO Reports
https://www.readbyqxmd.com/read/25534441/enhanced-microglial-activity-in-faah-animals
#18
F Ativie, O Albayram, K Bach, B Pradier, A Zimmer, A Bilkei-Gorzo
AIMS: Several lines of evidence suggest that the endocannabinoid system is involved in the regulation of glial activity. Enhanced levels of the endocannabinoid N-arachidonoyl ethanolamine (AEA, also referred to as anandamide) as well as non-cannabinoid lipids like palmitoylethanolamine (PEA) due to genetic deletion or pharmacologic blockade of its degrading enzyme fatty acid amide hydrolase (FAAH) reduced neuroinflammatory changes in models of neurodegeneration. Now we addressed the question if genetic deletion of FAAH also influences age-related neuroinflammation...
October 1, 2015: Life Sciences
https://www.readbyqxmd.com/read/25278116/advances-in-the-management-of-multiple-sclerosis-spasticity-multiple-sclerosis-spasticity-nervous-pathways
#19
Diego Centonze
BACKGROUND: Spasticity arises from hyperexcitability of the neural stretch reflex arc secondary to injury of the corticospinal tract. In response to injury, the density of glutamatergic inputs from afferent 1A fibers to motor neurons increases dramatically and adaptive changes occur in the morphology of microglia cells in the spinal cord. SUMMARY: Involvement of the endocannabinoid system in pathophysiological mechanisms responsible for spasticity has been demonstrated in animal models of MS...
2014: European Neurology
https://www.readbyqxmd.com/read/25269445/r-flurbiprofen-attenuates-experimental-autoimmune-encephalomyelitis-in-mice
#20
Katja Schmitz, Natasja de Bruin, Philipp Bishay, Julia Männich, Annett Häussler, Christine Altmann, Nerea Ferreirós, Jörn Lötsch, Alfred Ultsch, Michael J Parnham, Gerd Geisslinger, Irmgard Tegeder
R-flurbiprofen is the non-cyclooxygenase inhibiting R-enantiomer of the non-steroidal anti-inflammatory drug flurbiprofen, which was assessed as a remedy for Alzheimer's disease. Because of its anti-inflammatory, endocannabinoid-modulating and antioxidative properties, combined with low toxicity, the present study assessed R-flurbiprofen in experimental autoimmune encephalomyelitis (EAE) models of multiple sclerosis in mice. Oral R-flurbiprofen prevented and attenuated primary progressive EAE in C57BL6/J mice and relapsing-remitting EAE in SJL mice, even if the treatment was initiated on or after the first flare of the disease...
November 2014: EMBO Molecular Medicine
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