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


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.


image 10.4303/jdar/235648

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