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: 2578810
• 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/2578810
• 关键词: brain metabolism; fatty acid metabolism; glia; glucose metabolism; glycogen; laboratory rat; lactates; oxygen consumption; potassium

The traditional concept of a dynamic balance and stoichiometry between oxygen consumption and glucose utilization to meet the brain's energy demands to support its functional activity has been questioned because of recent studies reporting that glucose utilization is stoichiometrically in excess of oxygen consumption during and following cognitive challenges or sensory stimulation. It is now a common speculation that glycolysis is preferentially stimulated to support functional activity in brain and that oxidative metabolism is little, if at all affected. Increased channeling of glucose into non-oxidative pathways when the demand for energy is increased, while the oxygen supply is adequate, violates traditional concepts about energy metabolism. We have, therefore, examined in vivo the metabolism of [14C]glucose in rat brain when glucose consumption was increased by functional activation. We have found that labeling of the brain lactate pool was increased 3- fold during K+-stimulated metabolic activity. About 20% of the glucose taken up by brain was lost to the 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, 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, indicating stoichiometrically higher glucose utilization than oxygen consumption. We found, however, that glycogen, which is localized mainly in glial cells, is depleted by sensory functional activation, indicating that some, if not all, of the excess glucose utilization that persists following the functional activation can be explained by the diversion of glucose carbon to the replenishment of metabolic pools depleted by the energy demands of the functional and metabolic activations.

传统的动态平衡和化学计量的概念， 氧气消耗和葡萄糖利用，以满足大脑的能量 支持其职能活动的要求受到质疑， 最近的研究报告说，葡萄糖的利用是 化学计量地超过氧消耗， 认知挑战或感官刺激。如今，它是一种常见的 推测糖酵解被优先刺激以支持 大脑中的功能活动和氧化代谢很少，如果 完全不受影响。增加葡萄糖进入非氧化性 当对能量的需求增加时， 是足够的，违反了关于能量代谢的传统概念。我们 因此，在大鼠体内检测了[14 C]葡萄糖的代谢 当葡萄糖消耗增加时，大脑功能激活。 我们已经发现，大脑乳酸池的标记增加了3- 倍期间K+刺激的代谢活动。大约20%的葡萄糖 被大脑吸收的蛋白质以乳酸盐的形式流失到血液中， 数量必须从激活的组织转移到其他组织， 大脑区域。因此，中间代谢物在细胞内的运输 大脑可以是广泛的，这是一个新的，意想不到的发现。另一方面，在一项研究中， 在感觉刺激期间和之后，乳酸积累和流出， 尽管氧/葡萄糖摄取比 减少，表明化学计量上葡萄糖利用率高于 耗氧量然而我们发现， 主要存在于神经胶质细胞中，被感觉功能激活耗尽， 这表明，如果不是全部， 在功能激活后持续存在可以通过以下原因来解释： 将葡萄糖碳转移到代谢池的补充 被功能和代谢活化的能量需求耗尽。