Methamphetamine Injections Cause Widespread Increases in Caspase-8 Expression in the Mouse Brain
Author(s): Xiaolin Deng, Subramaniam Jayanthi, Michael T McCoy, Bruce Ladenheim, Richard Kyle Rothman, and Jean Lud Cadet
Abstract
Methamphetamine administration can cause neuronal apoptotic death in the rat brain via activation of the extrinsic cell death pathway (Fas ligand/Fas/caspase-8 cascade). In the present study, we injected mice with a toxic regimen of methamphetamine (10 mg/kg×4 given at 2-h intervals) to assess the role of the Fas ligand/Fas/caspase-8 death pathway in their brain. Methamphetamine did cause the appearance of TUNEL-positive cells in the frontal cortex, striatum, and hippocampus of these animals. The number of TUNEL-positive cells was higher in the striatum than in the frontal cortex and hippocampus. Immunohistochemical and immunoblot techniques revealed significant methamphetamine-induced increases in Fas ligand expression and diffuse appearance of the active caspase-8 in these brain regions. Taken together, our data suggest that methamphetamine can cause marked activation of the caspase-8-dependent death pathway in the brain.
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