Investigation of the epigenetic mechanism of swallowing and respiratory disturbances
| Project/Area Number |
23593045
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Orthodontic/Pediatric dentistry
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| Research Institution | Nihon University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
ASANO Masatake 日本大学, 歯学部, 准教授 (10231896)
SAIGUSA Tadashi 日本大学, 松戸歯学部, 准教授 (50277456)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2013: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2011: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
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| Keywords | 呼吸 / 嚥下 / 延髄 / 呼吸中枢 / GABA / GAD1 / MeCP2 / DNAメチル化 / 呼吸調節 / 無呼吸 / CpG |
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| Research Abstract |
Rett syndrome (RTT) is caused by mutations in the gene encoding methyl-CpG-binding protein 2 (MeCP2). Mecp2-null mice exhibit frequent apnea similar to that seen in RTT, but epigenetic mechanisms underlying the respiratory disturbances are not well known. Because GABAergic neurotransmission has been reported to be impaired in the brain of Mecp2-null mice, we measured glutamate decarboxylase 1 (GAD1) mRNA expression in the respiratory nuclei in the medulla oblongata, and found that GAD1 mRNA was significantly reduced in Mecp2-null mice compared to wild-type mice at 2 weeks of age (p < 0.05). Methylation analysis of CpGs in the GAD1 proximal promoter revealed differences of the sites of methylated CpG between Mecp2-null mice and wild-type mice, and highly methylated CpGs in the GAD1 promoter of Mecp2-null mice.
These results indicate that the altered GAD1 expression in the respiratory nuclei in the medulla may be responsible for the respiratory disturbances in Mecp2-null mice.
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Report
(4 results)
Research Products
(8 results)
