Effects of diazoxide on A-1-42-induced expression of the NR2B subunit in cultured cholinergic neurons

Abstract

The accumulation of amyloid-protein (A) is significant in the pathogenesis of Alzheimer's disease. Several previous studies indicate that the NR2B-containing N-methyl-D-aspartate receptors are critically involved in the A mediated disruption of neuronal function. Diazoxide (DZ), a highly selective drug capable of opening mitochondrial ATP-sensitive potassium channels, has neuroprotective effects against neuronal cell death. However, the mechanism by which DZ protects cholinergic neurons against A-induced cytotoxicity remains to be elucidated. The present study was designed to investigate the effects of DZ pretreatment against A-1-42induced expression of NR2B in order to gain novel insights into the neuroprotective mechanisms. Following exposure to A-1-42 for 24 h, the expression of the NR2B subunit remained unchanged compared with the control group. However, a significant increase in the expression of the NR2B subunit was observed following treatment with A-1-42 for 72 h (P<0.05); and the upregulation of the expression of the NR2B subunit was reversed by pretreatment with DZ (P<0.05). These results suggested that DZ may counteract A-1-42mediated cytotoxicity by alleviating the expression of NR2B.