论文部分内容阅读
Alcohol, a widely abused drug, has deleterious effects on the immature nervous system. This study investi-gates the effect of chronic in vitro ethanol exposure on the metabolism of immature rat cerebellar granular cells (CGCs) and on their response to oxygen-glucose deprivation (OGD). Primary CGC cultures were ex-posed to ethanol (100 mM in culture medium) or to control ethanol-free medium starting day one in vitro (DIV1). At DIV8, the expression of ATP synthase gene ATP5g3 was quantified using real-time PCR, then cultures were exposed to 3 hours of OGD or normoxic conditions. Subsequently, cellular metabolism was assessed by a resazurin assay and by ATP level measurement. ATP5g3 expression was reduced by 12-fold (P= 0.03) and resazurin metabolism and ATP level were decreased to 74.4 ± 4.6％ and 55.5 ± 6.9％, respectively after chronic ethanol treatment compared to control values (P < 0.01). Additionally, after OGD exposure of ethanol-treated cultures, resazurin metabolism and ATP level were decreased to 12.7 ± 1.0％ and 9.0 ± 2.0％from control values (P < 0.01). These results suggest that chronic ethanol exposure reduces the cellular ATP level, possibly through a gene expression down-regulation mechanism, and increases the vulnerability to oxygen-glucose deprivation. Thus, interventions which improve metabolic function and sustain ATP-levels could attenuate ethanol-induced neuronal dysfunction and should be addressed in future studies.