| 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 (2023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 / Neuroprotection / ChAT / Huntingtin / STB / 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, we clarified the relationships of STB/HAP1 with ChAT in the brainstem, particularly in motoneurons and autonomic neurons. In the second year, we further investigated the relationships of STB/HAP1 with ChAT in the forebrain. We found that the cholinergic neurons of MS, VDB, and LS that are mainly projected to the hippocampus and parahippocampal gyrus might be protected by STB/HAP1 to regulate the sensory-motor integration or cognition during neurodegenerative/psychotic stresses. In contrast, the STB/HAP1 and ChAT co-expression devoid area (e.g., CPU and cortex) might be more prone to neurodegeneration. In addition, we also clarified that HAP1 is highly expressed in the submucosal plexuses of the enteric nervous system and the lingual 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 objectives 1 and 2 of our current research, and the other objectives are progressing smoothly. We have presented our research findings at various regional, national, and international conferences. We have also published two articles in peer-reviewed international 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 Huntingtin in the brain and spinal cord.
2. We will clarify the immunohistochemical relationships of STB/HAP1 with the Serotonin in the brain.
3. 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.
4. The aged mouse is an excellent model for examining motor neuron degeneration vulnerability. We will also determine the changes in motor neuron number and motor function-related behavioral test battery comparison between aged-wild type and aged-HAP1-TG mice.
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