| 研究課題/領域番号 |
22K06792
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| 研究種目 |
基盤研究(C)
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| 配分区分 | 基金 |
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| 応募区分 | 一般 |
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| 審査区分 |
小区分48010:解剖学関連
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| 研究機関 | 山口大学 |
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研究代表者 |
イスラム エムディノビウル 山口大学, 大学院医学系研究科, 講師 (80759671)
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| 研究分担者 |
篠田 晃 山口大学, 大学院医学系研究科, 教授 (40192108)
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| 研究期間 (年度) |
2022-04-01 – 2025-03-31
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| 研究課題ステータス |
交付 (2022年度)
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| 配分額 *注記 |
4,290千円 (直接経費: 3,300千円、間接経費: 990千円)
2024年度: 1,300千円 (直接経費: 1,000千円、間接経費: 300千円)
2023年度: 1,430千円 (直接経費: 1,100千円、間接経費: 330千円)
2022年度: 1,560千円 (直接経費: 1,200千円、間接経費: 360千円)
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| キーワード | HAP1 / Stigmoid body / Motor neuron / Autonomic neuron / Motoneuron / Neurodegeneration |
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| 研究開始時の研究の概要 |
Stigmoid body (STB)/huntingtin-associated protein 1 (HAP1) can protect neurodegenerative apoptosis in vitro. In this study, we will examine the changes of autonomic neurons and their functions using our recently generated HAP1-KO mice, and will elucidate the differences in motor function behavior test battery between aged-wild-type mice and aged-motor-neuron-specific HAP1-TG mice that we genetically engineered. The outcomes of this study may shed light on yet-to-be-uncovered new diagnostic or therapeutic applications for certain neurodegenerative diseases.
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| 研究実績の概要 |
In the first year of our study, we clarified the neuroanatomical distribution of STB/HAP1 in the brainstem of adult mice. We also elucidated the relationships of STB/HAP1 with ChAT, with particular emphasis on autonomic and motor neurons. Our results suggest that cranial nerve motor nuclei might be more vulnerable to neurodegenerative stresses than STB/HAP1-expressing brainstem nuclei. In addition, we clarified the STB/HAP1 expression in the enteric and tongue autonomic ganglia.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
We have completed our first objective, which includes the relationships of STB/HAP1 with ChAT in the brainstem. We have published our data in peer-reviewed journals.
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| 今後の研究の推進方策 |
1. We will clarify the immunohistochemical relationships of STB/HAP1 with the causal agents of certain neurodegenerative diseases in vivo.
2. We will examine STB/HAP1-expression in autonomic ganglion and determine the autonomic neuron number changes in the CNS/PNS of HAP1-KO mice. Furthermore, we will compare autonomic function-related behavioral test batteries between wild-type and HAP1-KO mice.
3. Aged mouse is an excellent model to examine the vulnerability to motor neuron degeneration. We will also determine the changes in motor neuron number motor function-related behavioral test battery comparison between aged-wild type and aged-HAP1-TG mice.
4. The microbiota/gut-and-brain axis is an emerging and widely accepted concept. STB/HAP1 might affect microbiota colonization in the intestine, jeopardizing the neurodegeneration in ENS and CNS. Using HAP1-KO mice, we will examine the effects of STB/HAP1 on enteric neurons and the composition of gut microbiota.
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