| Project/Area Number |
21500353
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Keio University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
ISHIKAWA Mami 自治医科大学, 医学部, 准教授 (60212859)
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2011: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 脳血流代謝カップリング / 一酸化炭素 / 硫化水素 / ガスバイオロジー / heme oxygenase / 脳血流循環代謝 / 低酸素応答 / 質量分析イメージング / neurovascular coupling / cystathionine β-synthase |
|---|
| Research Abstract |
Enhancement of cerebral blood flow by hypoxia is critical for brain function, but signaling systems underlying its regulation have been unclear. We report a novel pathway mediating hypoxia-induced cerebral vasodilation in studies monitoring vascular disposition in cerebellar slices as well as in intact mouse brains employing two-photon intravital laser scanning microscopy. In this cascade, hypoxia elicits cerebral vasodilation via the coordinate actions of hydrogen sulfide(H_2S) formed by cystathionine.-synthase(CBS) and carbon monoxide(CO) generated by heme oxygenase(HO)-2. Hypoxia diminishes CO generation by HO-2, an oxygen(O_2) sensor. The constitutive CO physiologically inhibits CBS, so that hypoxia leads to increased levels of H_2S that mediate the vasodilation of pre-capillary arterioles. Mice with targeted deletion of HO-2 or CBS display impaired vascular responses to hypoxia. Thus, in intact adult brain cerebral cortex of HO-2-null mice, imaging mass spectrometry reveals an impaired ability to maintain ATP levels on hypoxia.
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