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首页> 外文期刊>The European Journal of Neuroscience >Cerebral glucose utilization in transgenic mice overexpressing heat shock protein 70 is altered by dizocilpine.
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Cerebral glucose utilization in transgenic mice overexpressing heat shock protein 70 is altered by dizocilpine.

机译:地佐西平改变了过表达热休克蛋白70的转基因小鼠中的大脑葡萄糖利用。

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摘要

Heat shock protein (HSP70), a member of the 70 kDa HSP superfamily, has been widely implicated in the cellular stress response to numerous insults. HSP70 may be a significant factor in cell survival following stresses such as cerebral ischaemia. The precise mechanisms by which HSP70 facilitates cell survival remain unclear. The aim of this study was to ascertain whether any differences in local cerebral glucose utilization (LCGU) existed between transgenic mice overexpressing HSP70 (HSP70 Tg) and wild- type littermate (WT) mice. LCGU was assessed using (14)C-2-deoxyglucose in HSP70 Tg and WT mice under basal conditions (intraperitoneal injection of saline) and during metabolic activation produced by NMDA receptor blockade (intraperitoneal injection of dizocilpine, 1 mg/kg). No significant alterations in LCGU were observed between saline injected HSP70 Tg and WT mice in any of the 35 brain regions analyzed. Dizocilpine injection produced significant heterogeneous alterations in LCGU in HSP70 Tg mice (24 of 35 brain regions) and in WT mice (22 of 35 brain regions) compared with saline injected mice. The distribution of altered LCGU produced by dizocilpine was similar in HSP70 Tg and WT mice. However in five brain regions, dizocilpine injected HSP70 Tg mice displayed significantly altered LCGU compared to dizocilpine injected WT mice (anterior thalamic nucleus +27%, dorsal CA1 stratum lacunosum molecularae +22%, dorsal CA1 stratum oriens + 14%, superior olivary body -26%, and the nucleus of the lateral lemniscus -16%). These data highlight that while overexpression of HSP70 transgene does not significantly alter LCGU in the basal state, mice overexpressing the HSP70 transgene respond differently to metabolic stress produced by NMDA receptor blockade in some important brain regions.
机译:热休克蛋白(HSP70)是70 kDa HSP超家族的成员,已广泛参与了对多种损伤的细胞应激反应。 HSP70可能是应激(例如脑缺血)后细胞存活的重要因素。 HSP70促进细胞存活的确切机制仍不清楚。这项研究的目的是确定过表达HSP70(HSP70 Tg)的转基因小鼠和野生型同窝仔(WT)小鼠之间局部脑葡萄糖利用(LCGU)是否存在任何差异。 LCGU是在基础条件下(腹膜内注射盐水)和在NMDA受体阻断产生的代谢活化过程中(腹膜内注射双唑西平1 mg / kg)在HSP70 Tg和WT小鼠中使用(14)​​C-2-脱氧葡萄糖评估的。在所分析的35个脑区中的任何一个中,注射盐水的HSP70 Tg与WT小鼠之间均未观察到LCGU的显着变化。与注射盐水的小鼠相比,地佐西平注射液在HSP70 Tg小鼠(35个脑区中的24个)和WT小鼠(35个脑区中的22个)中的LCGU产生了显着的异质性变化。在HSP70 Tg和WT小鼠中,地佐西平产生的改变的LCGU的分布相似。然而,在五个大脑区域中,与地佐西平注射的WT小鼠相比,地佐西平注射的HSP70 Tg小鼠表现出LCGU的显着改变(丘脑前核+ 27%,背侧CA1腔层+ 22%,背侧CA1层+ 14%,上橄榄岩体-占26%,而侧生盘状核为-16%)。这些数据强调,虽然HSP70转基因的过表达不会显着改变基础状态下的LCGU,但过表达HSP70转基因的小鼠对某些重要脑区域中NMDA受体阻滞产生的代谢应激反应不同。

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