COUPLING OF METABOLIC PROCESSES AND FUNCTIONAL ACTIVITY IN BRAIN

代谢过程与大脑功能活动的耦合

• 批准号: 5203816
• 负责人: G DIENEL
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5203816
• 关键词: bioenergetics; brain metabolism; calcium flux; calcium metabolism; carbon; cerebral cortex; enzyme activity; glia; glucose metabolism; glycogen; glycolysis; laboratory rat; lactates; neurons; oxygen consumption; potassium

The traditional concept of a dynamic balance between oxygen and glucose consumption to meet brain energy expenditures has been challenged by recent studies reporting that glucose utilization exceeds that for oxygen during and after mental testing and sensory stimulation. Others speculated that glycolysis is preferentially stimulated to support mental activity; increased channeling of glucose into non-oxidative pathways when the demand for energy is increased and when levels of oxygen in arterial blood are adequate is unexpected and is not understood. We are, therefore, elucidating metabolic requirements of functional activation to better understand the interactions between neurons and glia in working brain in vivo. We examined metabolism of [14C]glucose in rat brain when glucose consumption was increased and found that labeling of the brain lactate pool was increased 3-fold in K+-stimulated compared to resting tissue. Almost all of the excess glucose consumed in the activated tissue was converted to diffusible metabolites. About 20% of the glucose taken up by brain was lost to blood as lactate, and similar quantities must have been transported from activated tissue to other brain regions. Thus, trafficking of intermediary metabolites within the brain can be extensive; this is a new, unexpected finding. On the other hand, during and after sensory stimulation lactate accumulation and efflux to blood was much smaller even though the oxygen/glucose uptake ratio was reduced. We found that glycogen, which is localized mainly in glial cells, was depleted by sensory stimulation, indicating that replenishment of metabolic pools explains, in part, the excess consumption of glucose. Metabolism in both neurons and glia is altered when the brain responds to stimuli or carries out mental tasks and activities, and also during the recovery period following the activation period; the oxygen/glucose uptake ratio is influenced by both cell types.

传统的氧糖动态平衡概念 满足大脑能量消耗的消耗受到了挑战， 最近的研究报告说，葡萄糖的利用率超过了氧气的利用率 在精神测试和感官刺激期间和之后。别人 推测糖酵解被优先刺激，以支持精神 活性;增加葡萄糖进入非氧化途径的通道 当对能量的需求增加时， 动脉血是足够的，这是出乎意料的，也是不理解的。是的， 因此，阐明功能激活的代谢要求 为了更好地理解神经元和神经胶质在工作中的相互作用， 大脑在体内。我们检查了大鼠脑中[14 C]葡萄糖的代谢， 葡萄糖消耗增加，发现大脑的标记 与静息状态相比，K+刺激下乳酸池增加3倍 组织.几乎所有被激活的组织中消耗的多余葡萄糖 转化为可扩散的代谢物。大约20%的葡萄糖摄入量 大脑中的乳酸盐以乳酸盐的形式流失到血液中， 从激活的组织转移到大脑的其他区域。因此，在本发明中， 中间代谢物在脑内的运输可以是 广泛;这是一个新的，意想不到的发现。另一方面，在 感觉刺激后乳酸积累并流出血液 即使氧/葡萄糖摄取比降低， 我们发现，主要位于神经胶质细胞中的糖原， 由于感官刺激而耗尽，这表明 代谢池部分解释了葡萄糖的过度消耗。 当大脑做出反应时，神经元和神经胶质细胞的代谢都会发生变化 刺激或执行心理任务和活动，以及在 激活期之后的恢复期;氧/葡萄糖 摄取率受两种细胞类型的影响。