Methamphetamine induces oligodendroglial cell death in vitro

Genç, Kürşad; Kızıldağ, Sefa; Sonmez, Ulker; Yılmaz, Osman; Tugyan, Kazim; Ergur, Bekir Uğur; Sönmez, Ataç; Buldan, Zisan

doi:10.1016/s0006-8993(03)02890-7

Cited by 24 publications

(21 citation statements)

References 17 publications

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“…The 1-mM and 2-mM concentrations of Meth and MDMA were selected since they would achieve a minimal neurotoxic effect on primary cortical cells both for cell survival and protein proteolysis. It is worth noting that in most previous in-vitro drug-abuse studies drug concentrations needed to be between 3 and 5 mM to achieve similar neurotoxicity (Cadet et al, 1997 ;Deng et al, 2002, Genc et al, 2003, Jimenez et al, 2004Stumm et al, 1999). Neurotoxicity, as measured by the concentration of BDPs was more apparent after 48 h than 24 h and the results show dose dependency.…”

Section: Discussionmentioning

confidence: 93%

Calpain- and caspase-mediated αII-spectrin and tau proteolysis in rat cerebrocortical neuronal cultures after ecstasy or methamphetamine exposure

Warren

Zheng

Kobeissy

et al. 2006

Int. J. Neuropsychopharm.

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Abuse of 3,4-methylenedioxymethamphetamine (MDMA or Ecstasy) and methamphetamine (Meth or Speed) is a growing international problem with an estimated 250 million users of psychoactive drugs worldwide. It is important to demonstrate and understand the mechanism of neurotoxicity so potential prevention and treatment therapies can be designed. In this study rat primary cerebrocortical neuron cultures were challenged with MDMA and Meth (1 or 2 mM) for 24 and 48 h and compared to the excitotoxin N-methyl-D-aspartate (NMDA). The neurotoxicity of these drugs, as assessed by microscopy, lactate dehydrogenase release and immunoblot, was shown to be both dose-and time-dependent. Immunoblot analysis using biomarkers of cell death showed significant proteolysis of both aII-spectrin and tau proteins. Breakdown products of aII-spectrin (SBDPs) of 150, 145, and 120 kDa and tau breakdown products (TBDPs) of 45, 32, 26, and 14 kDa were observed. The use of the protease inhibitors calpain inhibitor SJA6017 and caspase inhibitors z-VAD-fmk and Z-D-DCB, attenuated drug-induced aII-spectrin and tau proteolysis. The calpain inhibitor reduced the calpain-induced breakdown products SBDP145 and TBDP14, but there was an offset increase in the caspase-mediated breakdown products SBDP120 and TBDP45. The caspase inhibitors, on the other hand, decreased SBDP120 and TBDP45. These data suggest that both MDMA and Meth trigger concerted proteolytic attacks of the structural proteins by both calpain and caspase family of proteases. The ability of the protease inhibitors to reduce the damage caused by these drugs suggests that the treatment arsenal could include similar drugs as possible tools to combat the drug-induced neurotoxicity in vivo.

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Section: Discussionmentioning

confidence: 93%

Calpain- and caspase-mediated αII-spectrin and tau proteolysis in rat cerebrocortical neuronal cultures after ecstasy or methamphetamine exposure

Warren

Zheng

Kobeissy

et al. 2006

Int. J. Neuropsychopharm.

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“…Methamphetamine has been shown to induce toxicity in vivo [27] and in vitro [37,38]. There is evidence that BDNF may play a neuroprotective role against drug toxicity [39].…”

Section: Discussionmentioning

confidence: 99%

Dose-Dependent Effects of Binge-Like Methamphetamine Dosing on Dopamine and Neurotrophin Levels in Rat Brain

2017

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This study investigated the acute effect of a dose range of low-to-moderate binge-like methamphetamine treatments on the regional expression of neurotrophin proteins in the brain and serum 2 h after the last dose, in addition to assessing the behavioural effects and dopamine neurotransmitter changes produced. Male Sprague-Dawley rats received 4 subcutaneous doses of methamphetamine (0.5, 1, 2, and 4 mg/kg, or saline as a control) 2 h apart. Methamphetamine had a dose-dependent stimulatory effect on locomotor activity over the 8 h of observation. A significant increase in dopamine concentration was observed in the frontal cortex with the highest dose of methamphetamine (2 h after the last dose). This effect was dose- and region-specific, as no significant increase was observed with lower doses, nor was a significant change observed in any other brain region tested. A similar dose- and region-specific increase in brain-derived neurotrophic factor (BDNF) was observed in the frontal cortex with the highest-dose regimen. No significant change occurred with lower doses of methamphetamine, or in any other brain region tested. A reduction in BDNF levels in the serum was also observed with the highest concentration, but not with lower doses. Collectively, this data highlights the importance of the frontal cortex in methamphetamine-induced effects, and also the similar dose-response effect of methamphetamine on dopamine and BDNF expression.

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“…Several studies have previously shown that METH can be toxic to different brain cells (Deng et al, 2002;Genc et al, 2003;Mandyam et al, 2007), but the direct effect of this drug on DG stem cells has never been addressed before. Thus, in the present study we started by evaluating the toxic effect of METH on DG stem cells by quantifying the number of positive cells for TUNEL and Sox2 (Figs.…”

Section: Methamphetamine Can Induce Dentate Gyrus Stem Cell Deathmentioning

confidence: 99%

Methamphetamine decreases dentate gyrus stem cell self-renewal and shifts the differentiation towards neuronal fate

et al. 2014

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Methamphetamine (METH) is a highly addictive psychostimulant drug of abuse that negatively interferes with neurogenesis. In fact, we have previously shown that METH triggers stem/progenitor cell death and decreases neuronal differentiation in the dentate gyrus (DG). Still, little is known regarding its effect on DG stem cell properties. Herein, we investigate the impact of METH on mice DG stem/progenitor cell self-renewal functions. METH (10nM) decreased DG stem cell self-renewal, while 1nM delayed cell cycle in the G0/G1-to-S phase transition and increased the number of quiescent cells (G0 phase), which correlated with a decrease in cyclin E, pEGFR and pERK1/2 protein levels. Importantly, both drug concentrations (1 or 10nM) did not induce cell death. In accordance with the impairment of self-renewal capacity, METH (10nM) decreased Sox2(+)/Sox2(+) while increased Sox2(-)/Sox2(-) pairs of daughter cells. This effect relied on N-methyl-d-aspartate (NMDA) signaling, which was prevented by the NMDA receptor antagonist, MK-801 (10μM). Moreover, METH (10nM) increased doublecortin (DCX) protein levels consistent with neuronal differentiation. In conclusion, METH alters DG stem cell properties by delaying cell cycle and decreasing self-renewal capacities, mechanisms that may contribute to DG neurogenesis impairment followed by cognitive deficits verified in METH consumers.

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Methamphetamine induces oligodendroglial cell death in vitro

Cited by 24 publications

References 17 publications

Calpain- and caspase-mediated αII-spectrin and tau proteolysis in rat cerebrocortical neuronal cultures after ecstasy or methamphetamine exposure

Calpain- and caspase-mediated αII-spectrin and tau proteolysis in rat cerebrocortical neuronal cultures after ecstasy or methamphetamine exposure

Dose-Dependent Effects of Binge-Like Methamphetamine Dosing on Dopamine and Neurotrophin Levels in Rat Brain

Methamphetamine decreases dentate gyrus stem cell self-renewal and shifts the differentiation towards neuronal fate

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