Proceedings of The Physiological Society
University College Dublin (2009) Proc Physiol Soc 15, PC206
Methamphetamine toxicity in PC12 cells is accompanied by an increase in BDNF: Possible neuroprotection.
A. M. Santos1,2, J. Kelly1, K. M. Doyle2
1. Pharmacology and Therapeutics, NUI Galway, Galway, Ireland. 2. Physiology, NUI Galway, Galway, Ireland.
Methamphetamine (MA) has been shown to induce toxicity in vivo and in vitro  affecting in particular, but not only, dopaminergic neurons . The molecular and cellular mechanisms involved in this process remain to be clarified. Previously, in this laboratory, we found that repeated MA administration increases BDNF levels in the frontal cortex and striatum of Sprague Dawley rats , which may be an attempt to protect the brain against MA toxicity. PC12 cells have dopaminergic characteristics  and is a widely used model. The objective of this study was to establish toxic doses of MA in PC12 cells and to correlate apoptotic/necrotic morphology with cell viability as measured by MTT assay, and BDNF levels, measured by ELISA. PC12 cells were seeded on poly-L-lysine coated well plates at a density of 5x 105/ml for ELISA and 2.5x 105/ml for morphology and MTT analysis. Preliminary data demonstrated that MA did not affect morphology, cell viability or BDNF expression in PC12 cells at sub-millimolar concentrations. Cells were treated with MA (1mM, 3mM, 6mM or 15mM), staurosporine (STS) 2mM (positive control known to induce apoptosis) or medium (negative control) for 24 hours. The results (see table) showed that methamphetamine reduced cell viability, induced apoptotic and necrotic cell death and increased BDNF expression in PC12 cells. This study shows that MA induced toxicity is accompanied by an increase in the expression of BDNF. Further elucidation of the mechanism by which MA reduces cell viability and induces cell death is needed, as is a better understanding of the role of BDNF in these events.
Where applicable, experiments conform with Society ethical requirements