title: Calpain and caspase proteolytic markers co-localize with rat cortical neurons after exposure to methamphetamine and MDMA.
abstract: Abuse of the club drugs Methamphetamine (Meth) and Ecstasy (MDMA) is an international problem. The seriousness of this problem is the result of what appears to be programmed cell death (PCD) occurring within the brain following their use. This follow up study focused on determining which cell types, neurons and/or glial cells, were affected in the brains of drug-injected rats. Two proteolytic enzyme families involved in PCD, calpains and caspases, were previously shown to be activated and to degrade the brain cytoskeletal associated protein alphaII-spectrin. Using methods employed and confirmed in traumatic brain injury (TBI) studies, rat brain tissues were examined, 24 and 48 h after Meth and MDMA exposure, for the activation of calpain-1 and caspase-3, and their subsequent alphaII-spectrin cleavage breakdown products (SBDPs), SBDP145, and SBDP120, respectively. Based upon our previous studies we know that activated calpain-1 and caspase-3 were up-regulated after drug use as were the levels of their cleaved SBDPs, SBDP145, and SBDP120, respectively, which is indicative of PCD. Here we show that activated calpain-1 and caspase-3 increases could be localized to neurons in the cortex where the products of their cleaved targets were found to be concentrated, particularly, to the axonal regions. These findings support the hypothesis that calpains and caspases mediate PCD in cortical neurons following club drug abuse and, more importantly, appear to contribute to the neuropathology suffered by abusers.
authors.affiliation: Center for Traumatic Brain Injury Studies, Department of Neuroscience, McKnight Brain Institute of the University of Florida, Gainesville, FL 32610, USA. warren@ufl.edu
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Warren
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Larner
authors.forename: Firas H
authors.initials: FH
authors.lastname: Kobeissy
authors.forename: Christina A
authors.initials: CA
authors.lastname: Brezing
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Jeung
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Hayes
authors.forename: Mark S
authors.initials: MS
authors.lastname: Gold
authors.forename: Kevin K W
authors.initials: KK
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000032:analysis; D015153:Blotting, Western; D002154:Calpain / Q000187:drug effects / Q000378:metabolism*; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects; D007150:Immunohistochemistry; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013049:Spectrin / Q000187:drug effects / Q000378:metabolism
chemical_list: D015415:Biomarkers; D000697:Central Nervous System Stimulants; D013049:Spectrin; D008694:Methamphetamine; D002154:Calpain; D053148:Caspase 3; D018817:N-Methyl-3,4-methylenedioxyamphetamine