Astrocytic glycogen-derived lactate fuels the brain during exhaustive exercise to maintain endurance capacity

Takashi Matsui, Hideki Omuro, Yu Fan Liu, Mariko Soya, Takeru Shima, Bruce S. Mcewen, Hideaki Soya

研究成果: ジャーナルへの寄稿学術誌査読

79 被引用数 (Scopus)

抄録

Brain glycogen stored in astrocytes provides lactate as an energy source to neurons through monocarboxylate transporters (MCTs) to maintain neuronal functions such as hippocampus-regulated memory formation. Although prolonged exhaustive exercise decreases brain glycogen, the role of this decrease and lactate transport in the exercising brain remains less clear. Because muscle glycogen fuels exercising muscles, we hypothesized that astrocytic glycogen plays an energetic role in the prolonged-exercising brain to maintain endurance capacity through lactate transport. To test this hypothesis, we used a rat model of exhaustive exercise and capillary electrophoresismass spectrometry-based metabolomics to observe comprehensive energetics of the brain (cortex and hippocampus) and muscle (plantaris). At exhaustion, muscle glycogen was depleted but brain glycogenwas only decreased. The levels of MCT2, which takes up lactate in neurons, increased in the brain, as did muscle MCTs. Metabolomics revealed that brain, but not muscle, ATP was maintained with lactate and other glycogenolytic/glycolytic sources. Intracerebroventricular injection of the glycogen phosphorylase inhibitor 1,4-dideoxy-1,4- imino-D-arabinitol did not affect peripheral glycemic conditions but suppressed brain lactate production and decreased hippocampal ATP levels at exhaustion. An MCT2 inhibitor, α-cyano-4-hydroxycinnamate, triggered a similar response that resulted in lower endurance capacity. These findings provide direct evidence for the energetic role of astrocytic glycogen-derived lactate in the exhaustive-exercising brain, implicating the significance of brain glycogen level in endurance capacity. Glycogen-maintained ATP in the brain is a possible defense mechanism for neurons in the exhausted brain.

本文言語英語
ページ(範囲)6358-6363
ページ数6
ジャーナルProceedings of the National Academy of Sciences of the United States of America
114
24
DOI
出版ステータス出版済み - 6月 13 2017
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