Cannabidiol in vivo blunts β-amyloid induced neuroinflammation by suppressing IL-1β and iNOS expression

Background and purpose: Pharmacological inhibition of beta-amyloid (A beta) induced reactive gliosis may represent a novel rationale to develop drugs able to blunt neuronal damage and slow the course of Alzheimer's disease (AD). Cannabidiol (CBD), the main non-psychotropic natural cannabinoid, exerts in vitro a combination of neuroprotective effects in different models of Ab neurotoxicity. The present study, performed in a mouse model of AD-related neuroinflammation, was aimed at confirming in vivo the previously reported antiinflammatory properties of CBD. Experimental approach: Mice were inoculated with human A beta (1-42) peptide into the right dorsal hippocampus, and treated daily with vehicle or CBD (2.5 or 10mgkg(-1), i.p.)for 7 days. mRNA for glial fibrillary acidic protein (GFAP) was assessed by in situ hybridization. Protein expression of GFAP, inducible nitric oxide synthase (iNOS) and IL-1 beta was determined by immunofluorescence analysis. In addition, ELISA assay of IL-1 beta level and the measurement of NO were performed in dissected and homogenized ipsilateral hippocampi, derived from vehicle and Ab inoculated mice, in the absence or presence of CBD. Key results: In contrast to vehicle, CBD dose-dependently and significantly inhibited GFAP mRNA and protein expression in A beta injected animals. Moreover, under the same experimental conditions, CBD impaired iNOS and IL-1 beta protein expression, and the related NO and IL-1 beta release. Conclusion and implications: The results of the present study confirm in vivo anti-inflammatory actions of CBD, emphasizing the importance of this compound as a novel promising pharmacological tool capable of attenuating A beta evoked neuroinflammatory responses.