Amphetamines induce apoptosis and regulation of bcl‐x splice variants in neocortical neurons

  • G. Stumm
    Department of Neuropathology Philipps‐University Marburg Germany
  • J. Schlegel
    Department of Neuropathology Philipps‐University Marburg Germany
  • T. Schäfer
    Institute of Forensic Medicine Philipps‐University Marburg Germany
  • C. Würz
    Department of Psychiatry Philipps‐University Marburg Germany
  • H. D. Mennel
    Department of Neuropathology Philipps‐University Marburg Germany
  • J.‐C. Krieg
    Department of Psychiatry Philipps‐University Marburg Germany
  • H. Vedder
    Department of Psychiatry Philipps‐University Marburg Germany

書誌事項

公開日
1999-06
権利情報
  • http://onlinelibrary.wiley.com/termsAndConditions#vor
DOI
  • 10.1096/fasebj.13.9.1065
公開者
Wiley

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説明

<jats:title>ABSTRACT</jats:title> <jats:p> Amphetamine analogs have emerged as popular recreational drugs of abuse. The number of reports of these substances producing severe acute toxicity and death is increasing. In ‘Ecstasy’ ‐associated deaths, focal necrosis in the liver and individual myocytic necrosis has been reported. Furthermore, serotonergic and dopaminergic neuronal cell damage has been observed in experimental amphetamine intoxication in laboratory animals. Here we demonstrate that subchronic exposure to D‐amphetamine, methamphetamine, methylenedioxyamphetamine, and methylenedioxymethamphetamine (‘Ecstasy’) results in significant neurotoxicity in rat neocortical neurons <jats:italic>in vitro</jats:italic> . This neuronal cell death is accompanied by endonucleosomal DNA cleavage and differential expression of anti‐ and proapoptotic bcl‐x <jats:sub>L/S</jats:sub> splice variants. In addition, we observed pronounced induction of cell stress‐associated transcription factor c‐jun and translation initiation inhibitor p97 after amphetamine treatment. These data support that the neurotoxic effects of different amphetamines are extended to rat neocortical neurons and that apoptotic pathways are involved in amphetamine‐induced neurotoxicity.—Stumm, G., Schlegel, J., Schäfer, T., Würz, C., Mennel, H. D., Krieg, J.‐C., Vedder, H. Amphetamines induce apoptosis and regulation of bcl‐x splice variants in neocortical neurons. <jats:italic>FASEB J.</jats:italic> 13, 1065–1072 (1999) </jats:p>

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