Concurrent calpain and caspase-3 mediated proteolysis of αII-spectrin and tau in rat brain after methamphetamine exposure: A similar profile to traumatic brain injury

• Published in: Life sciences (1973) 2005-12, Vol.78 (3), p.301-309
• Main Authors: Warren, Matthew W., Kobeissy, Firas H., Liu, Ming Cheng, Hayes, Ronald L., Gold, Mark S., Wang, Kevin K.W.
• Format: Article
• Language: English
• Subjects: Alpha-spectrin; Animals; Blotting, Western; Brain - drug effects; Brain - metabolism; Brain Injuries - enzymology; Brain Injuries - metabolism; Calpain; Calpain - metabolism; Caspase 3; Caspases; Caspases - metabolism; Cerebral cortex; Cysteine Endopeptidases - metabolism; Disease Models, Animal; Drug abuse; Electrophoresis, Polyacrylamide Gel; Hippocampus; Male; Methamphetamine; Methamphetamine - toxicity; Nerve Tissue Proteins - metabolism; Neurotoxicity Syndromes - enzymology; Neurotoxicity Syndromes - etiology; Neurotoxicity Syndromes - metabolism; Rats; Rats, Sprague-Dawley; Spectrin - metabolism; Tau protein; tau Proteins; Traumatic brain injury
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2005.04.058

Neurotoxicity in rat cortex and hippocampus following acute methamphetamine administration was characterized and compared to changes following traumatic brain injury. Doses of 10, 20, and 40 mg/kg of methamphetamine produced significant increases in calpain- and caspase-cleaved αII-spectrin and tau protein fragments, suggesting cell injury or death. Changes in proteolytic products were significantly increased over vehicle controls. Use of fragment specific biomarkers detected prominent calpain-mediated protein fragments in the cortex and hippocampus while caspase-mediated protein fragments were also detected in the hippocampus. Remarkably, proteolytic product increases at the 40 mg/kg dose after 24 h were as high as those observed in experimental traumatic brain injury. Use of calpain and caspase proteolytic inhibitors may be useful in preventing methamphetamine-induced neurotoxicity.