11_Martin-Moreno_CBD reduces microglial actiuvation rel Alzheimer's_Mol Pharm

11_Martin-Moreno_CBD reduces microglial actiuvation rel Alzheimer's_Mol Pharm

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Sheet1 Page 1 Molecular Pharmacology Fast Forward. Published on February 24, 2011 as doi:10.1124/mol.111.071290 MOL #71290 1 Cannabidiol and other cannabinoids reduce microglial activation in vitro and in vivo: relevance to Alzheimer& s disease Ana María Martín-Moreno*, David Reigada*, Belén.G.Ramírez, R. Mechoulam, Nadia Innamorato, Antonio Cuadrado and María L. de Ceballos Neurodenegeration Group, Dept. of Cellular, Molecular and Developmental Neurobiology, Instituto Cajal, CSIC, Doctor Arce, 37, 28002 Madrid, Spain AMM-M, DR, BGR, MLC Centro de Investigación en Red en Enfermedades Neurodegenerativas (CIBERNED) AMMM, DR, BGR, MLC, NI, AC Institute for Drug Research, Medical Faculty, Hebrew University, Jerusalem 91120, Israel RM Departamento de Bioquímica, Instituto de Investigaciones Biomédicas & Alberto Sols± UAMCSIC, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain NI, AC Copyright 2011 by the American Society for Pharmacology and Experimental Therapeutics. C MOL #71290 Running title: Effects of cannabinoids on microglial cell function Corresponding author: M.L.de Ceballos Neurodenegeration Group, Dept. of Cellular, Molecular and Developmental Neurobiology, Instituto Cajal, CSIC, Doctor Arce, 37, 28002 Madrid, Spain and CIBER de Enfermedades Neurodegenerativas (CIBERNED) Telephone:+34-91 5854716 Present address: DR Molecular Neuroprotection Group, Experimental Neurology Unit,Paraplejic National Hospital, Finca la Peraleda s/n, 45071 Toledo, Spain. Present address: BGR Unidad de Apoyo a la Investigación, Fundación MD Anderson Internacional España, C/Arturo Soria 270, 28033 Madrid, Spain. Nº text pages 31 Nº Figures 6 Nº References 40
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Sheet1 Page 2 Nº words Abstract 238 Nº of words Introduction 658 Nº of words Discussion 1357 Abbreviations: Aß, ß-amyloid peptide disease d MOL #71290 Abstract s disease (AD). Interestingly cannabinoids are neuroprotective by preventing ß-amyloid (Aß) induced microglial activation both in vitro and in vivo. On the other hand, the phytocannabinoid cannabidiol (CBD) has shown anti-inflammatory properties in different paradigms. In the present study we compared the effects of CBD with those of other cannabinoids on microglial cell functions in vitro and on learning behaviour and cytokine expression following Aß intraventricular administration to mice. CBD, WIN 55,212-2 (WIN), a mixed CB1/CB2 agonist, and JWH-133 (JWH), a CB2 selective agonist, concentration-dependently decreased ATP-induced (400 µM) increase in intracellular calcium ([Ca2+]i) in cultured N13 microglial cells and in rat primary microglia. In contrast HU-308 (HU), another CB2 agonist, was without effect. Cannabinoid and adenosine A2A receptors may be involved in the CBD action. CBD and WIN-promoted primary microglia migration was blocked by CB1 and/or CB2 antagonists. JWH and HU-induced migration was blocked by a CB2 antagonist only. All the cannabinoids decreased LPS-induced nitrite
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This note was uploaded on 08/14/2011 for the course GENETICS 2203 taught by Professor Athwal during the Spring '09 term at Temple.

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11_Martin-Moreno_CBD reduces microglial actiuvation rel Alzheimer's_Mol Pharm

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