Investigation of the epigenetic mechanism of swallowing and respiratory disturbances

吞咽和呼吸障碍的表观遗传机制研究

• 批准号: 23593045
• 负责人: SHIRAKAWA Tetsuo
• 金额: $ 3.49万
• 依托单位: Nihon University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23593045/
• 关键词: 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

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.

Rett综合征（RTT）是由编码甲基CpG结合蛋白2（MeCP2）的基因突变引起的。 Mecp2基因敲除小鼠表现出与RTT相似的频繁呼吸暂停，但呼吸紊乱的表观遗传机制尚不清楚。由于据报道Mecp 2基因敲除小鼠大脑中的GABA能神经传递受损，我们测量了延髓呼吸核中谷氨酸脱羧酶1（GAD 1）mRNA的表达，发现Mecp 2基因敲除小鼠中的GAD 1 mRNA在2周龄时比野生型小鼠显著降低（p < 0.05）。GAD 1近端启动子区CpG甲基化分析显示，Mecp 2基因敲除小鼠和野生型小鼠的CpG甲基化位点存在差异，而Mecp 2基因敲除小鼠GAD 1启动子区CpG甲基化程度较高，提示Mecp 2基因敲除小鼠延髓呼吸核团GAD 1表达的改变可能是导致呼吸功能紊乱的原因。

项目成果

Diurnal increase of apnea and reduced GAD1 mRNA expression in respiratory nuclei of Mecp2-deficient mice

Mecp2 缺陷小鼠呼吸暂停的昼夜增加和呼吸核中 GAD1 mRNA 表达减少

• 发表时间: 2013
• 作者: Nishiyama M;Asano M;Iwasa S;Suzuki A;Wada T;Takiguchi H;Shirakawa T
• 通讯作者: Shirakawa T

Therapeutic management of malocclusion caused by a lip sucking habit in a girl with Rett syndrome.

患有雷特综合征的女孩因吸唇习惯引起的咬合不正的治疗管理。

• 发表时间: 2012
• 作者: Nakamura Y;Kawakami T;Karibe H;米倉智子,本間宏実,桜井敦朗,森口美津子,見明康雄,豊澤悟,新谷誠康;Shirakawa Tetsuo
• 通讯作者: Shirakawa Tetsuo

レット症候群モデルの呼吸異常

雷特综合征模型中的呼吸异常

• 发表时间: 2011
• 作者: Nakamura Y;Kawakami T;Karibe H;白川哲夫
• 通讯作者: 白川哲夫

Abnormal breathing and occlusal disharmony in a mouse model of Rett syndrome

雷特综合征小鼠模型的呼吸异常和咬合不协调

• 发表时间: 2012
• 作者: Nishiyama M;Wada T;Takiguchi H;Takamori K;Asano M;Iwasa S;Suzuki A;Shirakawa T
• 通讯作者: Shirakawa T

Histaminergic effects on the frequency of repetitive spike firing in rat insular cortex

组胺能对大鼠岛叶皮层重复尖峰放电频率的影响

• 发表时间: 2012
• 期刊: Neurosci Lett
• 影响因子: 2.5
• 作者: Takei H;Song L;Ebihara K;Shirakawa T;Koshikawa N;Kobayashi M
• 通讯作者: Kobayashi M