| Project/Area Number |
22K15656
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 51030:Pathophysiologic neuroscience-related
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| Research Institution | Hyogo Medical University |
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Principal Investigator |
段 ショウキ 兵庫医科大学, 薬学部, 博士研究員 (20910607)
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| Project Period (FY) |
2022-04-01 – 2025-03-31
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| Project Status |
Granted (Fiscal Year 2022)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2024: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | SNS / IBS / Micro-inflammation / Visceral pain / sympathetic nervous / eosinophil |
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| Outline of Research at the Start |
Patients who suffer from irritable bowel syndrome often exhibit abnormal psychological profiles like depression, which is closely related to the sympathetic nervous system (SNS) activity. SNS-immune interaction is considered important to chronic disease development. Recently, we successfully established a maternal separation-induced IBS animal model, which showed increased activity of SNS and micro-inflammation in the gastrointestinal (GI) tract. The proposed project aimed to investigate whether and how SNS modulates eosinophil in the GI tract, and their involvement in pathophysiology of IBS.
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| Outline of Annual Research Achievements |
This research aims to investigate the relationship and potential mechanism between sympathetic nervous system (SNS) and micro-inflammation. In this year, I established the maternal separation (MS) model to mimic IBS. This model showed visceral hypersensitivity to colorectal distention, which is the main pathophysiology of IBS. I confirmed that there is micro-inflammation in colon of MS rats at adulthood by flowcytometry method and IHC. Besides, I researched the SNS activity. The ELISA result showed that NE concentration in serum increased in the MS rats compared with control. Neural activation markers are higher in MS model rats compared with control. Taken together, I confirmed that MS rats showed over activation of SNS. In addition, I applied the 6-OHDA to degenerate the SNS, the pharmacological data suggested that SNS played a role in immune cell alteration in colon. I also started to establish the genetic modulation approach to specifically modulation SNS activity.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
In this year, I established the IBS model with micro-inflammation and over activation of SNS by MS stress. I pharmacologically confirmed that SNS activation modulate immune alteration in colon. By those data, I achieved the first step of the project.
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| Strategy for Future Research Activity |
In the next year, I will focus on the genetic modulation of peripheral SNS by DBH-cre mice with AAV-PHP.S infection. Using this method, I will specifically activate or inhibit the peripheral SNS and check the immune alteration.
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