| Project/Area Number |
20K11551
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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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| Review Section |
Basic Section 59040:Nutrition science and health science-related
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| Research Institution | International Christian University (2022-2023)
Ochanomizu University (2020-2021) |
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Principal Investigator |
グホ サビン 国際基督教大学, 教養学部, 准教授 (30453179)
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| Co-Investigator(Kenkyū-buntansha) |
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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| Project Period (FY) |
2020-04-01 – 2025-03-31
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| Project Status |
Granted (Fiscal Year 2023)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | Nanoplastic / Neuroinflammation / Area postrema / Oral exposure / Gene expression / NTS / hear rate / osmoregulation / Heart rate / Urine osmolality / Microglia reactivity / nanoplastics / oral exposure / heart rate / urine osmolality / area postrema / microglia morphology / nanoplastics exposure / blood pressure / cardiovascular centers / autonomic functions / circumventricular organs / inflammatory response |
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| Outline of Research at the Start |
This research plan aims at investigating whether a chronic oral exposure to plastic nanoparticles affects central nervous system in rats. The study will focus on molecular and functional characteristics of brains areas involved in the regulation of autonomic functions.
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| Outline of Annual Research Achievements |
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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| Current Status of Research Progress |
Current Status of Research Progress
4: Progress in research has been delayed.
Reason
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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| Strategy for Future Research Activity |
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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