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A Mechanism for the Inhibition of Neural Progenitor Cell Proliferation by Cocaine

A Mechanism for the Inhibition of Neural Progenitor Cell Proliferation by Cocaine

  1. Expat98
    A Mechanism for the Inhibition of Neural Progenitor Cell Proliferation by Cocaine

    Lee C-T, Chen J, Hayashi T, Tsai S-Y, Sanchez JF, et al.
    PLoS Med 5(6): e117.

    Prenatal exposure of the developing brain to cocaine causes morphological and behavioral abnormalities. Recent studies indicate that cocaine-induced proliferation inhibition and/or apoptosis in neural progenitor cells may play a pivotal role in causing these abnormalities. To understand the molecular mechanism through which cocaine inhibits cell proliferation in neural progenitors, we sought to identify the molecules that are responsible for mediating the effect of cocaine on cell cycle regulation.

    Our results demonstrate that down-regulation of cyclin A underlies cocaine-induced proliferation inhibition in neural progenitors. The down-regulation of cyclin A is initiated by N-oxidative metabolism of cocaine and consequent ER stress. Inhibition of cocaine N-oxidative metabolism by P450 inhibitors may provide a preventive strategy for counteracting the adverse effects of cocaine on fetal brain development.