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: 6162918
• 负责人: L SOKOLOFF
• 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/6162918
• 关键词: brain metabolism; fatty acid metabolism; glia; glucose metabolism; glycogen; laboratory rat; lactates; oxygen consumption; potassium

It has been generally believed for some time that there is a dynamic balance and stoichiometry between oxygen consumption and glucose utilization to meet the brain's energy demands to support its functional activity. This concept has recently been challenged because of 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 functional activity in brain is supported by energy derived from glycolysis and little, if at all, from oxidative metabolism. Under conditions of limited oxygen supply, this would be expected, but for this to happen in the presence of adequate oxygen violates traditional concepts about energy metabolism. We have, therefore, examined in vivo the metabolism of [14C]glucose in rat brain in conditions in which glucose consumption was increased by functional activation. We 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 following sensory stimulation lactate accumulation in the brain and loss to the blood were much smaller even though the oxygen/glucose uptake ratio was reduced, indicating that glucose utilization exceeded the stoichiometric equivalent of the 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 activation's.

一段时间以来，人们普遍认为存在着一种动态的 耗氧量和葡萄糖之间的平衡和化学计量 利用以满足大脑支持其功能的能量需求 活动。这个概念最近因研究而受到挑战 报告称葡萄糖利用率按化学计量超过 认知挑战或感官挑战期间和之后的耗氧量 刺激。现在普遍的猜测是，功能活动 大脑由糖酵解产生的能量支持，如果有的话，也很少 所有这些，都来自氧化代谢。有限氧气条件下 供应，这是预料之中的，但是要在存在的情况下发生这种情况 充足的氧气违反了传统的能量概念 代谢。因此，我们检查了体内代谢 在葡萄糖消耗量减少的条件下，大鼠脑中的[14C]葡萄糖 通过功能激活而增加。我们发现大脑的标签 在 K+- 刺激代谢过程中，乳酸池增加了 3 倍 活动。大脑吸收的葡萄糖大约有20%被损失掉了 血液中含有乳酸，并且类似数量的血液必须是从 激活其他大脑区域的组织。因此，贩运 大脑内的中间代谢物可以是广泛的，一种新的， 意外的发现。另一方面，在感觉期间和之后 刺激乳酸在大脑中的积累和血液中的流失 即使氧气/葡萄糖摄取比率降低，也要小得多， 表明葡萄糖利用率超过化学计量 相当于耗氧量。然而，我们发现糖原， 主要位于神经胶质细胞中，被感觉耗尽 功能激活，表明部分（如果不是全部）多余的 功能激活后持续的葡萄糖利用 可以通过葡萄糖碳转移到补充来解释 代谢池因功能和功能的能量需求而耗尽 代谢激活。