抄録
Methamphetamine (METH), widely abused in Taiwan, is a long lasting derivative of d-amphetamine that has led to rapidly spreading health problems due to the high incidence of neurological and psychiatric complications associated with the consumption of this psychostimulant. Repeated exposure to recreational doses of METH produces persistent neurotoxicity to presynaptic monoamine terminals. However, the molecular and cellular mechanism underlying this process has remained unclear. In this study, we established a cell-culture model of METH-induced neuronal damage in human neuroblastoma SH-SY5Y cells. After exposure to 250 microg/ml of METH, we found the following intracellular alterations: (1) Mitochondrial membrane potential showed a 40% decreased after a 2hr treatment. (2) Intracellular mitochondrial mass showed a 50% increased after a 24hr treatment. (3) Cell cycle was arrested at G0/G1 phase after a 24hr treatment. (4) DNA fragmentation (sub-G1) was significantly increased and cytoplasmic vacuoles as well as plasma membrane blebbing were observed after a 48 hr treatment. (5) Cell death was observed in a dose- and time-dependent manner. In addition, we found that pretreatment with 5 mM N-acetyl-cysteine (NAC) prevented the METH-induced cell death. However, pretreatment with 25 to 100 microM baicalein only prevented the cell death induced by the 250 microg/ml METH treatment for 24 hr. Baicalein could delay, but not completely prevent, the METH-induced neurotoxicity in the SH-SY5Y cells. Based on these observations, we suggest that the loss of mitochondrial membrane potential and cell death may play a critical role in the METH-induced neurotoxicity.
