Mechanism of increase in brain-aromatic monoamines after peripheral administration of sepiapterin

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K20429
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Functional basic dentistry
• Research Institution: Nihon University
• Principal Investigator: OHASHI Akiko 日本大学, 歯学部, 助教 (00571019)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: セロトニン / ドーパミン / モノアミン合成促進 / テトラヒドロビオプテリン補充

Outline of Final Research Achievements

Serotonin (5HT) biosynthesis in the brain is controlled by tetrahydrobiopterin (BH4) level. Peripheral dosing of sepiapterin (SP) as a prodrug of BH4 to mice showed significant rise in BH4, 5HT, DA and their metabolites in the brain time- and dose-dependently. 5HT synthesis in a culture cell was promoted by added SP in the medium, while more than 20-fold higher concentration of BH4 was required for the same enhancement. SP showed adequate permeation across in vitro BBB model. These results suggested that not-all SP converted to BH4 in the periphery but partly reached the brain as SP.

Free Research Field

薬理学