- 作者: Chih-Jung YAO ; Chii-Wann LIN ; Shoei-Yn LIN-SHIAU
- 中文摘要: When mature cerebellar granule neurons (CGN) grown in high K+ (25 mM K+, HK)-serum containing medium are subjected to the HK/serum deprivation, they are destined for neuronal death. In this study, we attempted to elucidate the roles of endoplasmic reticular (ER) Ca2+-store and co-cultured astrocytes in HK/serum deprivation induced neuronal death. Thapsigargin (TG), an inhibitor of ER Ca2+-ATPase was simultaneously applied with normal K+ (5 mM K+, NK) serum free medium, and its effects on neuronal death in either astrocyte-poor or astrocyte-rich culture were examined. By means of the fura-2 microfluorimetric technique, we monitored the changes of the intracellular Ca2+ concentration, [Ca2+]i, associated with neuronal death under various treatments. The results obtained showed that in astrocyte-poor cultures of mature CGN (10 days in vitro, DIV), the basal level of [Ca2+]i markedly decreased from 184.plmin.5 to 89.7.plmin.5 nM 24 h after HK/serum deprivation. Although treatment with TG slightly increased the [Ca2+]i to 117.6.plmin.4 nM, the survival rate of the neurons was even worse; it was reduced from 49.plmin.4% to 28.plmin.2%. In the astrocyte-rich cultures, HK/serum deprivation also caused a profound reduction of neuronal [Ca2+]i from 166.plmin.3 to 90.2.plmin.6 nM, accompanied by even more serious neuronal death (95.5.plmin.1%). On the other hand, treatment with TG in astrocyterich cultures further lowered the [Ca2+]i to 65.plmin.2 nM but markedly improved the neuronal survival rate from 4.5.plmin.1% to 60.plmin.2% in a concentration-dependent manner. The strong implication of these findings is that ER Ca2+-store and astrocytes participate in modulating the responses of neurons to stress stimulation.
- 英文摘要: --
- 中文關鍵字: cerebellar granule neurons, thapsigargin, astrocyte, intracellular Ca2+, survival
- 英文關鍵字: --