Calpain and caspase proteolytic markers co-localize with rat cortical neurons after exposure to methamphetamine and MDMA.
Matthew W Warren, Stephen F Larner, Firas H Kobeissy, Christina A Brezing, Jennifer A. Jeung, Ronald L Hayes, Mark S. Gold, Kevin K W Wang
Acta neuropathologica September 2007 DOI: 10.1007/s00401-007-0259-9 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Population | Rat brain tissues |
| Duration | 24 and 48 hours after drug exposure |
| Topics | MDMA |
| Key findings | Activated calpain-1 and caspase-3 were localized to cortical neurons, with cleaved products concentrated in axonal regions, supporting the hypothesis that these enzymes mediate programmed cell death in cortical neurons following Meth and MDMA exposure. |
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.
Comparable studies
Other observational and cohort studies on MDMA, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Subjective Reports of the Effects of MDMA in a Clinical Setting Individuals who took MDMA in a clinical setting | 1986 | Observational study | |
| Memory impairment in abstinent MDMA ("Ecstasy") users Abstinent MDMA users | 1998 | Observational cohort | |
| Impaired cognitive performance in drug free users of recreational ecstasy (MDMA) Otherwise healthy young people | 2000 | Observational | |
| The Psychological and Physiological Effects of MDMA on Normal Volunteers Older, more educated, drug-experienced individuals | 1986 | Observational cohort | |
| Cognitive performance in recreational users of MDMA or 'ecstasy': evidence for memory deficits Young people who were regular or novice MDMA users, or non-users | 1998 | Observational cohort | n = 30 |
Citations in the library
Cited by 12
- MDMA Increases Glutamate Release and Reduces Parvalbumin-Positive GABAergic Cells in the Dorsal Hippocampus of the Rat: Role of Cyclooxygenase Journal of Neuroimmune Pharmacology November 17, 2012
- The intriguing effects of ecstasy (MDMA) on cognitive function in mice subjected to a minimal traumatic brain injury (mTBI). Psychopharmacology April 1, 2011
- Effects of Stress and MDMA on Hippocampal Gene Expression BioMed Research International 2014
- Longitudinal Examination of Learning and Memory in Rats Following Adolescent Exposure to 3,4-Methylenedioxymethamphetamine or 5-Methoxy-N,N-Diisopropyltryptamine Journal of Behavioral and Brain Science 2017
- 3,4-Methylenedioxymethamphetamine causes cytotoxicity on 661W cells through inducing macrophage polarization. Cutaneous and Ocular Toxicology June 2018
and 7 more in the library
Cites 9
- Positron emission tomographic evidence of toxic effect of MDMA (“Ecstasy”) on brain serotonin neurons in human beings The Lancet October 1, 1998
- 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings Psychopharmacology March 15, 2006
- The abused drug MDMA (Ecstasy) induces programmed death of human serotonergic cells The FASEB Journal February 1, 1997
- Neurotoxic effects of MDMA (“ecstasy”) administration to neonatal rats International Journal of Developmental Neuroscience June 5, 2004
- Studies of MDMA-Induced Neurotoxicity in Nonhuman Primates: A Basis for Evaluating Long-Term Effects in Humans PsycEXTRA Dataset 1989
and 4 more in the library