Canna~Fangled Abstracts

Regulatory role of the Cannabinoid-2 receptor in stress-induced neuroinflammation in mice.

By January 28, 2014 No Comments
2014 Jan 28. doi: 10.1111/bph.12607. [Epub ahead of print]

pm8Regulatory role of the Cannabinoid-2 receptor in stress-induced neuroinflammation in mice.

Abstract

BACKGROUND AND PURPOSE:

Stress-exposure produces excitoxicity and neuroinflammation, contributing to the cellular damage observed in stress-related neuropathologies. The endocannabinoid system is present in stress-responsive neural circuits and it is emerging as a homeostatic system. The aim of this study was to elucidate the possible regulatory role of cannabinoid-2 receptor in stress-induced excitotoxicity and neuroinflammation.

EXPERIMENTAL APPROACH:

Different genetic and pharmacological approaches were used: 1) Wild type (WT), transgenic over-expressing CB2 receptor (CB2xP) and CB2 receptor knockout (CB2-KO) mice were exposed to immobilization/acoustic stress (2h/day for 4 days), and 2) the CB2 receptor agonist JWH-133 was administered daily (2 mg kg-1 , i.p.) to WT and CB2 receptor-KO animals.

KEY RESULTS:

Stress-induced HPA axis activation was not modified by CB2 receptor manipulations. JWH-133 treatment or overexpression of CB2 resulted in an increase of control levels of glutamate uptake, which is then reduced by stress exposure back to control levels. JWH-133 prevented the stress-induced increase in the cytokines TNF-α and MCP-1, the nuclear factor kappa B, the enzymes inducible nitric oxide synthase 2 and cyclooxygenase-2 and the cellular oxidative/nitrosative damage (lipid peroxidation) in brain frontal cortex. CB2xP mice displayed anti-inflammatory/neuroprotective actions similar to those observed in JWH-133 pre-treated animals. Conversely, CB2-KO mice experiments indicated that the lack of CB2 receptor exacerbated stress-induced neuroinflammatory responses and validated the CB2 receptor-dependent effects of JWH-133.

CONCLUSIONS AND IMPLICATIONS:

These results suggest that pharmacological manipulation of CB2 receptor is a potential therapeutic strategy for the treatment of stress-related pathologies with a neuroinflammatory component, such as depression.
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KEYWORDS:

CB2 receptor, CB2xP mice, JWH-133, brain frontal cortex, excitotoxicity, neuroinflammation, stress

PMID:

 

24467609

 

[PubMed – as supplied by publisher]
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