COUPLING OF METABOLIC PROCESSES AND FUNCTIONAL ACTIVITY IN BRAIN

人们普遍认为，大脑的能量 需求通常是通过消耗氧气和 化学计量比的葡萄糖，用于完全氧化 葡萄糖转化为氧气和水。这一信念最近受到了挑战 因为PET研究报告葡萄糖的使用量超过了 认知挑战期间的等量耗氧量 感官刺激。这导致了现在流行的猜测 大脑的功能活动是由来自于 糖酵解和少量的，如果有的话，来自氧化代谢。在……下面 在氧气供应有限的情况下，这是意料之中的，但对于 在氧气充足的情况下发生这种情况违反了传统 能量代谢的概念。因此，我们已经研究了 清醒大鼠体内[14C]葡萄糖在大鼠脑内的代谢 在葡萄糖消耗量增加了 功能激活。脑动静脉血氧分压、葡萄糖和 乳酸的差异和总的和14C标记的乳酸水平， 糖原，和大脑中的葡萄糖，在每个时期结束时 对患者进行功能状态测量。脑乳酸的~(14)C标记 在K+刺激的代谢活动中，Pool增加了3倍。 大约20%被大脑摄取的葡萄糖流失到血液中 作为乳酸盐，而且类似数量的物质一定是从 激活的组织转移到其他脑区。因此，贩运 大脑中的中间代谢物可以是广泛的，一种新的， 出乎意料的发现。在感觉刺激期间和之后 乳酸在大脑中的积聚和对血液的损失很大 更小即使氧/葡萄糖摄取比降低， 表明葡萄糖的利用率超过了化学计量比 相当于刺激期的耗氧量 。此外，大脑中的糖原水平，主要局限于 在感觉功能激活过程中，星形胶质细胞减少。 然而，在感觉刺激的恢复过程中， 氧/葡萄糖比率上升到远高于 完整的化学计量比，表明耗氧量更大 而不是等量的葡萄糖利用率。因此，这些结果表明， 功能激活仅依赖于糖酵解是不正确的 而不是氧化代谢。两国间的明显脱钩 氧糖代谢只是暂时的；过量的葡萄糖 利用会导致葡萄糖代谢物在体内积累 功能激活期间的中间池，然后 在较长时间内进一步氧化成二氧化碳和水 在康复期间。关于这部作品的手稿已出版或 都在印刷中。这个项目现在在这里停止，因为 从事这项工作的专业工作人员已经离开了 目前正在他们的新实验室继续这些研究 地点。出版物：Dienel，G.A.，Cruz，N.F.，Adachi，K. Sokoloff，L.和Holden，J.E.(1997)局部脑的测定 血糖水平与[14C]甲基葡萄糖：葡萄糖供应的影响 和需求。我是J.Physiol。(内分泌。梅塔布。36)、273： E839-E849。马德森、P.L.、克鲁兹、索科洛夫、L和迪内尔， G.A.(在媒体)感觉期间大脑氧/葡萄糖比率较低 刺激并在恢复期间高于正常水平：过量葡萄糖 刺激过程中的消耗量不会被乳酸盐计算在内 从脑组织流出或积聚在脑组织中。J·雷伯。血液流动 梅塔布。(1998年8月14日获接纳)。

It has been generally believed that the brain's energy demands were normally met by the consumption of oxygen and glucose in stoichiometric amounts for the complete oxidation of glucose to oxygen and water. This belief was recently challenged because of PET studies reporting that glucose is used in excess of equivalent oxygen consumption during cognitive challenges or sensory stimulation. This has led to the now popular speculation that functional activity in brain is supported by energy derived from glycolysis and litt,e 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 O2 violates traditional concepts of energy metabolism. We have, therefore, examined in conscious rats in vivo the metabolism of [14C]glucose in rat brain under conditions in which glucose consumption was increased by functional activation. Cerebral arteriovenous O2 glucose, and lactate differences and total and 14C-labeled levels of lactate, glycogen, and glucose in the brain at the end of the period for each functional state were measured. 14C- 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. 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 during the stimulation period . Also, brain levels of glycogen, which is localized mainly in astroglial cells, was diminished during sensory functional activation. During recovery from the sensory stimulation, however, the oxygen/glucose ratio rose to much higher levels that that for complete stoichiometry, indicating greater oxygen consumption than equivalent glucose utilization. These results, therefore, show that it is not true that functional activaty depends only on glycolytic and not oxidative metabolism. The apparent uncoupling between oxygen glucose metabolism is only temporal; the excess glucose utilization leads to accumulation of glucose metabolites in intermediate pools during functional activation which are then oxidized further to CO2 and H2O over an extended period of time during recovery. Manuscripts on this work have been published or are in press. This project is now discontinued here because the professional staff members who were working on it have left the laboratory and are now continuing these studies at their new locations. Publications Dienel, G.A., Cruz, N.F., Adachi, K., Sokoloff, L., and Holden, J.E. (1997) Determination of local brain glucose level with [14C]methylglucose: Effects of glucose supply and demand. Am J. Physiol. (Endocrinol. Metab. 36), 273: E839-E849. Madsen, P.L., Cruz, N.F., Sokoloff, L, and Dienel, G.A. (In press) Cerebral oxygen/glucose ratio is low during sensory stimulation and rises above normal during recovery: Excess glucose consumption during stimulation is not accounted for by lactate efflux from or accumulation in brain tissue. J. Cereb. Blood Flow Metab. (Accepted August 14, 1998).