In this study, cerebellar granule neurons were used to examine the role of nitric oxide on cell survival. The N-methyI-D-aspartic acid receptor antagonist, MK-801, and the soluble guanylate cyclase antagonist, 1H-[1, ...In this study, cerebellar granule neurons were used to examine the role of nitric oxide on cell survival. The N-methyI-D-aspartic acid receptor antagonist, MK-801, and the soluble guanylate cyclase antagonist, 1H-[1, 2, 4]oxadiazolo-[4, 3-a] quinoxalin-1 -one, decreased cell viability, induced caspase-3, and decreased phosphorylated-Akt levels, suggesting that blockade of nitric oxide production promotes apoptosis of differentiating cerebellar granule neurons. After administration of sodium nitroprusside, an endogenous nitric oxide donor, cell viability recovered, caspase-3 expression was decreased, and phosphorylated-Akt levels increased. This study provides direct evidence that nitric oxide can sustain the survival of developing cerebellar granule neurons in vitro through the nitric oxide-Akt pathway. Moreover, endogenous nitric oxide exerts these effects in a cyclic guanosine monophosphate-dependent manner while exogenous nitric oxide does so in a cyclic guanosine monophosphate-independent manner.展开更多
γ-amidobutyric acid (GABA) is a major inhibitory neurotransmitter in the central nervous system and mediates fast synaptic inhibition through GABAA and GABAC
基金the National Natural Science Foundation of China, No. 81070995Guangdong Provincial Science Foundation, No.05001726, 1050175
文摘In this study, cerebellar granule neurons were used to examine the role of nitric oxide on cell survival. The N-methyI-D-aspartic acid receptor antagonist, MK-801, and the soluble guanylate cyclase antagonist, 1H-[1, 2, 4]oxadiazolo-[4, 3-a] quinoxalin-1 -one, decreased cell viability, induced caspase-3, and decreased phosphorylated-Akt levels, suggesting that blockade of nitric oxide production promotes apoptosis of differentiating cerebellar granule neurons. After administration of sodium nitroprusside, an endogenous nitric oxide donor, cell viability recovered, caspase-3 expression was decreased, and phosphorylated-Akt levels increased. This study provides direct evidence that nitric oxide can sustain the survival of developing cerebellar granule neurons in vitro through the nitric oxide-Akt pathway. Moreover, endogenous nitric oxide exerts these effects in a cyclic guanosine monophosphate-dependent manner while exogenous nitric oxide does so in a cyclic guanosine monophosphate-independent manner.
文摘γ-amidobutyric acid (GABA) is a major inhibitory neurotransmitter in the central nervous system and mediates fast synaptic inhibition through GABAA and GABAC