Interactions among glucose, lactate and adenosine regulate energy substrate utilization in hippocampal cultures

Interactions among glucose, lactate and adenosine regulate energy substrate utilization in hippocampal cultures
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DOI:
10.1016/s0006-8993(01)02218-1
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发表时间:
2001-04-27
期刊:
影响因子:
2.9
通讯作者:
Sapolsky, RM
Sapolsky, RM
中科院分区:
医学3区
文献类型:
--
作者:
Bliss, TM;Sapolsky, RM

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葡萄糖是正常成人大脑活动的主要能量来源。然而,在缺氧缺血后,神经元似乎更倾向于将胶质源性乳酸作为能量底物。我们研究了影响培养的海马神经元从葡萄糖到乳酸能量转换的因素,重点研究了在缺氧缺血过程中乳酸、葡萄糖和腺苷浓度的生理变化。我们发现,在乳酸和葡萄糖的典型基础浓度下,乳酸对葡萄糖摄取没有影响。然而,在缺氧缺血后发现的这些代谢物的浓度下,乳酸抑制了葡萄糖的摄取。反过来,无论葡萄糖和乳酸浓度如何,葡萄糖对乳酸的利用都没有影响。此外,我们发现在低血糖条件下,腺苷对葡萄糖摄取有轻微但显著的抑制作用。此外,腺苷增加了乳酸的利用率。因此,葡萄糖、乳酸和腺苷的相对浓度,可以指示海马体的能量状态。影响所使用的能源基材。这些结果支持这样的观点,即在缺氧缺血后,神经元偏向于乳酸而不是葡萄糖的利用,这是通过一系列调节步骤实现的。(C)2001 Elsevier Science B.V.保留所有权利。
Glucose is the major energy source during normal adult brain activity. However, it appears that glial-derived lactate is preferred as an energy substrate by neurons following hypoxia-ischemia, We examined factors influencing this switch in energetic bias from glucose to lactate in cultured hippocampal neurons, focusing on the effects of the physiological changes in lactate, glucose and adenosine concentrations seen during hypoxia-ischemia. We show that with typical basal concentrations of lactate and glucose, lactate had no effect on glucose uptake. However, at the concentrations of these metabolites found after hypoxia-ischemia, lactate inhibited glucose uptake. Reciprocally, glucose had no effect on lactate utilization regardless of glucose and lactate concentrations. Furthermore, we find that under hypoglycemic conditions adenosine had a small, but significant, inhibitory effect on glucose uptake. Additionally, adenosine increased lactate utilization. Thus, the relative concentrations of glucose, lactate and adenosine, which are indicative of the energy status of the hippocampus. influence which energy substrates are used. These results support the idea that after hypoxia-ischemia, neurons are biased in the direction of lactate rather than glucose utilization and this is accomplished through a number of regulatory steps. (C) 2001 Elsevier Science B.V. All rights reserved.