2013 Fiscal Year Final Research Report
C-type natriuretic peptide modulates permeability of the blood–brain barrier
| Project/Area Number |
23592100
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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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| Research Field |
Cerebral neurosurgery
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| Research Institution | Kagoshima University |
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Principal Investigator |
NAGAYAMA Tetsuya 鹿児島大学, 医歯(薬)学総合研究科, 客員研究員 (40336334)
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| Co-Investigator(Kenkyū-buntansha) |
MIYATA Atsurou 鹿児島大学, 医歯学総合研究科, 教授 (60183969)
KAMBE Yuki 鹿児島大学, 医歯学総合研究科, 助教 (60549913)
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| Project Period (FY) |
2011 – 2013
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| Keywords | 血液脳関門 / C型ナトリウム利尿ペプチド / zonula occludens-1 / JunD / ドラッグデリバリーシステム |
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| Research Abstract |
C-type natriuretic peptide (CNP) is abundant in brain, but its effect on blood-brain barrier (BBB) permeability has not been clarified yet. Here, we examined this effect. Transendothelial electrical resistance (TEER) of in vitro BBB model, was significantly dose dependently decreased by CNP. CNP treatment reduced both the messenger RNA and protein expressions of zonula occludens-1 (ZO-1). The effects on TEER, mRNA, and protein expressions of ZO-1 were mimicked by cyclic GMP (cGMP) analog 8-bromo-cGMP and reversed by protein kinase G (PKG) inhibitor Rp-8-CPT-cGMPS, thus implying the role of PKG and cGMP signaling in BBB function. In vivo study of mouse brain by fluorimetric analysis with intravenous administration of sodium fluorescein also showed a significant increase in BBB permeability by CNP. These findings suggest that CNP modulates the BBB permeability by altering ZO-1.
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