| 研究課題/領域番号 |
20K11551
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| 研究機関 | 国際基督教大学 |
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研究代表者 |
グホ サビン 国際基督教大学, 教養学部, 准教授 (30453179)
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| 研究分担者 |
宮本 泰則 お茶の水女子大学, ヒューマンライフイノベーション研究所, 教授 (50272737)
和気 秀文 順天堂大学, スポーツ健康科学部, 教授 (50274957)
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| 研究期間 (年度) |
2020-04-01 – 2025-03-31
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| キーワード | Nanoplastic / Neuroinflammation / Area postrema / Oral exposure / Gene expression / NTS / hear rate / osmoregulation |
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| 研究実績の概要 |
We examined the effects of oral nanoplastic exposure on cardiovascular parameters and cellular/molecular characteristics within the rat area postrema (AP, a blood-brain barrier (BBB)-free region) and Nucleus Tractus Solitarius (NTS, located beyond the BBB). Male Wistar rats, aged five weeks, were administered daily doses of either positively or negatively charged polystyrene nanoparticles (NPs) for two months. NPs altered heart rate and osmoregulation and induced microglial reactivity in the AP and NTS, regardless of the presence of a BBB. However, NPs induced a 61% decrease in cFos gene expression and a 13% increase in VEGF gene expression within the AP but not the NTS. This suggests that BBB-free areas react to NPs through neuroprotective mechanisms, which may alter their function.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
4: 遅れている
理由
The FY2023 plan aimed to analyze changes in the expression of potential neuroinflammatory markers at the transcript level using RT-qPCR in AP and NTS total RNAs. Our objective also involved microinjecting the altered products of these candidate genes (or their ligands) into the AP of anesthetized rats to assess their impact on cardiovascular parameters. However, challenges in identifying differentially expressed genes in the AP, coupled with time constraints from other commitments, impeded a comprehensive gene expression analysis. Additionally, to compare the molecular impact of NP treatment on BBB-protected areas versus non-protected areas, we examined the gene expression of these candidates in two other cardiovascular centers, namely the hypothalamus and the NTS, both protected by a BBB.
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| 今後の研究の推進方策 |
In FY2024, due to limited experimentation in FY2023, further investigation into the inflammatory status of the AP, NTS, and hypothalamus will be conducted at the molecular level. We will continue examining neuroinflammatory marker expression via RT-qPCR in these regions. Candidate molecules or their ligands showing differential gene expression in NP-exposed rat APs will be microinjected into anesthetized rat APs, and their role in regulating cardiovascular parameters will be acutely assessed. If successful, siRNA will be used to chronically silence the expression of targeted AP molecules to identify their functional roles in cardiovascular regulation in freely moving animals.
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| 次年度使用額が生じた理由 |
Part of the unused budget from FY2023 will be allocated towards purchasing additional primers and RT-qPCR kits to sustain ongoing experiments to identify gene expression changes induced by NP exposure in the AP, NTS, and hypothalamus. Another part of the FY2024 budget will be utilized to purchase rats (n=18), peptides, and siRNA essential for investigating the functional roles of candidate molecules identified through RT-qPCR experiments. The remaining budget will cover the publication fee for disseminating the resulting data.
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