Integrative Medicine > Cannabinoids

Abstract

Cannabinoids Protect Astrocytes from Ceramide-induced Apoptosis through the Phosphatidylinositol 3-Kinase/Protein Kinase B Pathway 

Teresa Gómez del Pulgar, María L. de Ceballos, Manuel Guzmán, and Guillermo Velasco

From the Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, 28040 Madrid [TGDP, MG, GV] and Neurodegeneration Group, Cajal Institute, CSIC, 28002 Madrid, Spain [MLC]. [GV]: To whom correspondence should be addressed: Dept. of Biochemistry and Molecular Biology I, School of Biology, Complutense University, 28040 Madrid, Spain. Tel.: 34 913944668; Fax: 34 913944672; E-mail: gvd@bbm1.ucm.es.

Cannabinoids, the active components of marijuana and their endogenous counterparts, exert many of their actions on the central nervous system by binding to the CB₁ cannabinoid receptor. 
Different studies have shown that cannabinoids can protect neural cells from different insults. 
However, those studies have been performed in neurons, whereas no attention has been focused on glial cells. 
Here we used the pro-apoptotic lipid ceramide to induce apoptosis in astrocytes, and we studied the protective effect exerted by cannabinoids. 
Results show the following: 
(i) cannabinoids rescue primary astrocytes from C₂-ceramide-induced apoptosis in a dose- and time-dependent manner; 
(ii) triggering of this anti-apoptotic signal depends on the phosphatidylinositol 3-kinase/protein kinase B pathway; 
(iii) ERK and its downstream target p90 ribosomal S6 kinase might be also involved in the protective effect of cannabinoids; and 
(iv) cannabinoids protect astrocytes from the cytotoxic effects of focal C₂-ceramide administration in vivo. 
In summary, results show that cannabinoids protect astrocytes from ceramide-induced apoptosis via stimulation of the phosphatidylinositol 3-kinase/protein kinase B pathway. 
These findings constitute the first evidence for an "astroprotective" role of cannabinoids.