Changes in IP 3R1 and SERCA2b mRNA levels in the gerbil brain after chronic ethanol administration and transient cerebral ischemia-reperfusion

Abstract

Despite epidemiological studies indicating a positive relationship between alcohol and stroke, little is known with regard to effect of chronic alcohol on neuronal injury after stroke. In this study, we examined the effect of chronic ethanol on mRNA levels of sarcoplasmic or endoplasmic Ca 2+-ATPase (SERCA2b) and inositol 1,4,5-triphosphate receptor (IP 3R1) in gerbils subjected to global cerebral ischemia induced by ligation of both common carotid arteries. Gerbils were given daily by intragastric intubation either a liquid diet containing ethanol (4 g/kg) or the same diet with an isocaloric amount of sucrose for 35 days. They were subsequently subjected to a 5 min ischemic insult followed by reperfusion for 48 h. In agreement with other studies, ischemic insult caused significant decreases ( P<0.05) in mRNA levels of both IP 3R1 and SERCA2b in the hippocampal CA1 region but not in the dentate gyrus. Nevertheless, despite a significant ( P<0.05) decrease in SERCA2b mRNA in the Purkinje neurons, chronic ethanol did not alter the expression of this mRNA species in the hippocampal CA1 neurons nor did it alter the decrease in SERCA2b mRNA due to cerebral ischemic insult. Since IP 3R1 and SERCA2b are key mediators for regulation of intracellular Ca 2+ stores, the decrease in SERCA2b mRNA but not IP 3R1 mRNA in cerebellar neurons may be an important mechanism underlying alteration of calcium homeostasis and cerebellar degeneration upon chronic ethanol consumption.