title: Cannabinoid receptor 2 deficiency results in reduced neuroinflammation in an Alzheimer's disease mouse model.
abstract: Several studies have indicated that the cannabinoid receptor 2 (CB2) plays an important role in neuroinflammation associated with Alzheimer's disease (AD) progression. The present study examined the role of CB2 in microglia activation in vitro as well as characterizing the neuroinflammatory process in a transgenic mouse model of AD (APP/PS1 mice). We demonstrate that microglia harvested from CB2(-/-) mice were less responsive to pro-inflammatory stimuli than CB2(+/+) microglia, based on the cell surface expression of ICAM and CD40 and the release of chemokines and cytokines CCL2, IL-6, and TNFα. Transgenic APP/PS1 mice lacking CB2 showed reduced percentages of microglia and infiltrating macrophages. Furthermore, they showed lowered expression levels of pro-inflammatory chemokines and cytokines in the brain, as well as diminished concentrations of soluble Aβ 40/42. The reduction in neuroinflammation did not affect spatial learning and memory in APP/PS1*CB2(-/-) mice. These data suggest a role for the CB2 in Alzheimer's disease-associated neuroinflammation, independent of influencing Aβ-mediated pathology and cognitive impairment.
authors.affiliation: Institute of Molecular Psychiatry, University of Bonn, Bonn, Germany; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
authors.forename: Anne-Caroline
authors.initials: AC
authors.lastname: Schmöle
authors.affiliation: Institute of Molecular Psychiatry, University of Bonn, Bonn, Germany.
authors.forename: Ramona
authors.initials: R
authors.lastname: Lundt
authors.affiliation: Institute of Molecular Psychiatry, University of Bonn, Bonn, Germany.
authors.forename: Svenja
authors.initials: S
authors.lastname: Ternes
authors.affiliation: Institute of Molecular Psychiatry, University of Bonn, Bonn, Germany.
authors.forename: Önder
authors.initials: Ö
authors.lastname: Albayram
authors.affiliation: Life and Medical Sciences (LIMES) Institute, Genomics and Immunoregulation, University of Bonn, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Ulas
authors.affiliation: Life and Medical Sciences (LIMES) Institute, Genomics and Immunoregulation, University of Bonn, Germany.
authors.forename: Joachim L
authors.initials: JL
authors.lastname: Schultze
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
authors.forename: Daniele
authors.initials: D
authors.lastname: Bano
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Nicotera
authors.affiliation: Institute of Molecular Psychiatry, University of Bonn, Bonn, Germany; Department of Psychiatry, University Münster, Münster, Germany; Cluster of Excellence EXC 1003, Cells in Motion, Münster, Germany.
authors.forename: Judith
authors.initials: J
authors.lastname: Alferink
authors.affiliation: Institute of Molecular Psychiatry, University of Bonn, Bonn, Germany. Electronic address: a.zimmer@uni-bonn.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Zimmer
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D003071:Cognition; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D018836:Inflammation Mediators / Q000378:metabolism; D008822:Mice, Transgenic; D017628:Microglia / Q000473:pathology*; D043885:Receptor, Cannabinoid, CB2 / Q000172:deficiency / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D018932:Chemokine CCL2; D018925:Chemokines; C571431:Cnr2 protein, mouse; D016207:Cytokines; D018836:Inflammation Mediators; D043885:Receptor, Cannabinoid, CB2
keywords: Alzheimer's disease; CB2; CCL2; Endocannabinoid system; Microglia; Neuroinflammation