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We studied lactate uptake and intracellular metabolism in the mouse brain using hyperpolarized C magnetic resonance spectroscopy (MRS). Following the intravenous injection of hyperpolarized [1-C]lactate, we observed that the distribution of the C label between lactate and pyruvate, which has been shown to be representative of their pool size ratio, is different in NMRI and C57BL/6 mice, the latter exhibiting a higher level of cerebral lactate dehydrogenase A ( Ldha) expression. On the basis of this observation, and an additional set of experiments showing that the cerebral conversion of [1-C]lactate to [1-C]pyruvate increases after exposing the brain to ultrasound irradiation that reversibly opens the BBB, we concluded that lactate transport is rate-limited by the BBB, with a 30% increase in lactate uptake after its disruption. 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Hyperpolarized 13C magnetic resonance spectroscopy reveals the rate-limiting role of the blood-brain barrier in the cerebral uptake and metabolism of L-lactate in vivo.
https://repo.qst.go.jp/records/49068
https://repo.qst.go.jp/records/49068e3be15fb-1ddc-4208-aa5a-f103619bc3e4
Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2018-05-29 | |||||
タイトル | ||||||
タイトル | Hyperpolarized 13C magnetic resonance spectroscopy reveals the rate-limiting role of the blood-brain barrier in the cerebral uptake and metabolism of L-lactate in vivo. | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
アクセス権 | ||||||
アクセス権 | metadata only access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
著者 |
Takado, Yuhei
× Takado, Yuhei× Cheng, Tian× A M Bastiaansen, Jessica× A I Yoshihara, Hikari× Lanz, Bernard× Mishkovsky, Mor× Lengacher, Sylvain× Comment, Arnaud× Takado, Yuhei |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | The dynamics of l-lactate transport across the blood-brain barrier (BBB) and its cerebral metabolism are still subject to debate. We studied lactate uptake and intracellular metabolism in the mouse brain using hyperpolarized C magnetic resonance spectroscopy (MRS). Following the intravenous injection of hyperpolarized [1-C]lactate, we observed that the distribution of the C label between lactate and pyruvate, which has been shown to be representative of their pool size ratio, is different in NMRI and C57BL/6 mice, the latter exhibiting a higher level of cerebral lactate dehydrogenase A ( Ldha) expression. On the basis of this observation, and an additional set of experiments showing that the cerebral conversion of [1-C]lactate to [1-C]pyruvate increases after exposing the brain to ultrasound irradiation that reversibly opens the BBB, we concluded that lactate transport is rate-limited by the BBB, with a 30% increase in lactate uptake after its disruption. It was also deduced from these results that hyperpolarized C MRS can be used to detect a variation in cerebral lactate uptake of <40 nmol in a healthy brain during an in vivo experiment lasting only 75 s, opening new opportunities to study the role of lactate in brain metabolism. | |||||
書誌情報 |
ACS chemical neuroscience 巻 9, 号 11, p. 2554-2562, 発行日 2018-05 |
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出版者 | ||||||
出版者 | American Chemical Society. | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 1948-7193 | |||||
PubMed番号 | ||||||
識別子タイプ | PMID | |||||
関連識別子 | 29771492 | |||||
DOI | ||||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1021/acschemneuro.8b00066 | |||||
関連サイト | ||||||
識別子タイプ | URI | |||||
関連識別子 | https://pubs.acs.org/doi/10.1021/acschemneuro.8b00066 |