Title

Seasonal Patterns Of Body Temperature Daily Rhythms In Group-Living Cape Ground Squirrels Xerus Inauris

Keywords

Cannabinoids; LPS; Microglial activation; NADPH oxidase; Oxidative stress; Proinflammatory cytokines

Abstract

We investigated the effects of synthetic cannabinoids, WIN55,212-2 and HU210, on LPS-injected rat substantia nigra in vivo. Intranigral injection of LPS resulted in a significant loss of nigral dopaminergic (DA) neurons, as determined by Nissl staining and TH immunohistochemistry. LPS-induced neurotoxicity was accompanied by microglial activation, as demonstrated by OX-42 immunohistochemistry. In parallel, Western blot analysis, ELISA assay and hydroethidine histochemistry revealed activation of NADPH oxidase, as demonstrated by increased translocation of the cytosolic proteins p47 phox and p67phox, generation of reactive oxygen species (ROS) and increased level of proinflammatory cytokines (TNF-α and IL-1β), where degeneration of nigral DA neurons was evident. Interestingly, WIN55,212-2 and HU210 increased the survival of nigral DA neurons at 7 days post-LPS treatment. Consistent with these results, cannabinoids inhibited activation of NADPH oxidase, ROS production and production of proinflammatory cytokines in the rat SN. The present data suggest that cannabinoids may be beneficial for the treatment of neurodegenerative diseases, such as PD, that are associated with microglial activation. © 2012 Elsevier B.V.

Publication Date

4-27-2012

Publication Title

PLoS ONE

Volume

7

Number of Pages

-

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1371/journal.pone.0036053

Socpus ID

84860439546 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/84860439546

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