2023 Fiscal Year Final Research Report
Treatment with growth factor prosaposin in a mammalian model of spina bifida
| Project/Area Number |
21K09324
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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 56020:Orthopedics-related
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| Research Institution | Oita University |
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Principal Investigator |
KHAN SAKIRUL 大分大学, グローカル感染症研究センター, 講師 (70746867)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | Spina Bifida Aperta / Chicken model / Mammalian model / Prosaposin / Neurotrophic factor / Therapeutic potentiality |
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| Outline of Final Research Achievements |
Currently, no effective therapeutics are available for spina bifida aperta (SBA) that causes fetal and pediatric deaths or lifelong neurological disabilities. The applicant confirmed the therapeutic potential of prosaposin-derived 18-mer peptide (PS18) in a chicken model of SBA. In fact, the intra-amniotic treatment with PS18 had a protective effect against SBA-induced secondary spinal injuries and rescued neurological function. Thus, PS18 may be useful for treating SBA-induced or other nervous system injuries. To confirm it in mammalian models, this study attempted to develop SBA in mice by congenital Zika virus (ZIKV) infection, as ZIKV causes various birth defects. ZIKAV was inoculated to pregnant mice, and the fetuses were checked to assess the development of SBA. Although no fetus showed SBA-like malformation after being congenital challenged with ZIKV, this study found that ZIKV infection caused smaller body and skull size and damage in the brain of fetuses.
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| Free Research Field |
神経科学 (Neuroscience)
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は二分脊椎症（SBA）哺乳類モデルにおけるプロサポシン由来18merペプチド（PS18）の治療効果を評価する研究である。ジカウイルス（ZIKV）は神経管欠損関連の先天性奇形を引き起こすことから、本研究ではZIKV先天性感染によるSBAマウスモデルの作出を目指した。結果としてSBAのような奇形は認められなかったが、ZIKV感染によって胎児が発育不良となり脳組織障害が生じた。このことから、本モデルは、ZIKVの胎児における発病メカニズム研究への応用が期待される。また、ニワトリモデルではPS18が神経保護効果を示したことから、脊髄損傷等に対する治療効果が認められれば社会的意義は極めて大きい。
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