Cannabinoid receptor 2 deficiency results in reduced neuroinflammation in an Alzheimer’s disease mouse model.. Mus musculus

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 ofAD (APP/PS1mice). 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 CB2showed reduced percentages of microglia and infiltrating macrophages. Furthermore, they showed lowered expression levels of pro-inflammatory chemokines and cytokine 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. Overall design: Primary microglia generated from 1-5 days old C57BL/6J (CB2+/+) pups were treated for 16h with LPS (100n/ml) and IFNγ (20 ng/ml)) or for 48 h with Interleukin-4 (IL-4) (100 U/ml). After harvesting, cells were immediately lysed in Trizol (Invitrogen) before storage at -80°C for RNA isolation.