Cannabinoid receptor 2 deficiency results in reduced neuroinflammation in an Alzheimer's disease mouse model

Autor: Judith Alferink, Thomas Ulas, Andreas Zimmer, Pierluigi Nicotera, Svenja Ternes, Anne-Caroline Schmöle, Daniele Bano, Joachim L. Schultze, Ramona Lundt, Onder Albayram
Rok vydání: 2015
Předmět:
Aging
Chemokine
psychology [Alzheimer Disease]
genetics [Alzheimer Disease]
Receptor
Cannabinoid
CB2
Cognition
pathology [Brain]
Cannabinoid receptor type 2
Cells
Cultured
Chemokine CCL2
Microglia
biology
metabolism [Chemokine CCL2]
General Neuroscience
pathology [Microglia]
Brain
deficiency [Receptor
Cannabinoid
CB2]
Endocannabinoid system
medicine.anatomical_structure
Cnr2 protein
mouse
Disease Progression
Cytokines
lipids (amino acids
peptides
and proteins)
Tumor necrosis factor alpha
Chemokines
Inflammation Mediators
Genetically modified mouse
metabolism [Amyloid beta-Peptides]
Mice
Transgenic
CCL2
Alzheimer Disease
medicine
Animals
ddc:610
Neuroinflammation
metabolism [Receptor
Cannabinoid
CB2]
Amyloid beta-Peptides
business.industry
metabolism [Inflammation Mediators]
metabolism [Chemokines]
metabolism [Cytokines]
Disease Models
Animal
nervous system
metabolism [Brain]
Immunology
biology.protein
Neurology (clinical)
Geriatrics and Gerontology
business
Developmental Biology
Zdroj: Neurobiology of aging 36(2), 710-719 (2015). doi:10.1016/j.neurobiolaging.2014.09.019
ISSN: 0197-4580
Popis: 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.
Databáze: OpenAIRE
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