Delta-9-Tetrahydrocannabinol (THC) Protects Partly against Demyelination by Modulating the Inflammatory Response: An In Vitro Study in Aggregating Brain Cell Cultures
- *Corresponding Author:
- Florianne Monnet-Tschudi
Department of Physiology, University of Lausanne
7, rue du Bugnon, CH-1005 Lausanne, Switzerland
Tel: +41 21 692 55 20
Fax: +41 21 692 55 05
E-mail: [email protected]
Received date: February 08, 2012; Accepted date: March 26, 2012; Published date: March 28, 2012
Citation: Defaux A, Schiffrin M, Vorlet-Fawer L, Spiehlmann A, Giroud C, et al. (2012) Delta-9-Tetrahydrocannabinol (THC) Protects Partly against Demyelination by Modulating the Inflammatory Response: An In Vitro Study in Aggregating Brain Cell Cultures. J Clinic Toxicol S6:002. doi: 10.4172/2161-0495.S6-002
Copyright: © 2012 Defaux A, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Delta 9-tetrahydrocannabinol (THC) has been proposed as therapeutic agent in the treatment of multiple sclerosis. In the present study, we examined whether a modulation of brain inflammation by THC may protect against demyelination. Myelinating aggregating brain cell cultures were subjected to demyelination by a repeated treatment (3x) with the two inflammatory agents interferon-γ (IFN-γ) and lipopolysaccharide (LPS). The effects of THC on an acute inflammatory response were also examined by treating the aggregates with a single application of the two inflammatory agents. THC effects on the demyelinating process and on several mediators of the inflammatory response were analyzed. THC treatment partially prevented the decreased immunoreactivity for MBP, and the decrease in MBP content measured by immunoblotting. It prevented IFN-γ + LPS-induced microglial reactivity; and decreased the IFN-γ + LPS-induced increased phosphorylation of p44/42 MAP kinase. The other inflammatory markers, i-NOS and TNF-α mRNA expression, and p38 MAP kinase phosphorylation were downregulated by THC treatment following a single application of the inflammatory agents, but not after repeated applications. THC protected partially against the IFN-γ + LPS-induced demyelination. The protective effect of THC on IFN-γ + LPS-induced demyelination may be due to a decrease of the inflammatory response. However, the anti-inflammatory effect of THC on some inflammatory markers is lost when the inflammatory response is more prominent and of longer duration, suggesting either that the anti-inflammatory effect of a molecule may depend on the properties of the inflammatory response, or that the anti-inflammatory potential of THC decreases in case of repeated exposure.