Journal
BRAIN RESEARCH
Volume 1451, Issue -, Pages 110-116Publisher
ELSEVIER
DOI: 10.1016/j.brainres.2012.02.058
Keywords
Cannabinoids; LPS; Microglial activation; NADPH oxidase; Oxidative stress; Proinflammatory cytoldnes
Categories
Funding
- Kyung Hee University [KHU-20080277]
Ask authors/readers for more resources
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 immunohistochemisty. 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 p67(Phox), generation of reactive oxygen species (ROS) and increased level of proinflammatory cytokines (TNF-alpha and IL-1 beta), 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 cytoldnes 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. (C) 2012 Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available