2023 Fiscal Year Annual Research Report
Treatment with growth factor prosaposin in a mammalian model of spina bifida
| Project/Area Number |
21K09324
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| Research Institution | Oita University |
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Principal Investigator |
カーン シャキル 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 Annual Research Achievements |
Neural tube defects (NTDs) cause fetal and pediatric deaths or lifelong neurological disabilities. No effective treatment is currently available for NTDs. We found therapeutic potential with prosaposin-derived 18-mer peptide (PS18) in a surgery-induced chicken model of spina bifida aperta (SBA), the severe type of NTDs. In fact, SBA chicks that received PS18 exhibited relatively normal walking and sensorimotor responses, reduced pain-associated behavior, and improved bladder and bowel movements in postnatal life (Khan et al., iScience 2023; IF: 6.1).
To aim for clinical application, evaluation of the effect of PS18 in mammalian models of NTDs is necessary. In this regard, we tried to develop a mouse model of SBA by congenital Zika virus (ZIKV) infection as ZIKV causes neurological defects. In this study, STAT1 knockout pregnant mice were used. Timing of breeding was determined in mice by identifying vaginal plugs, which signified 0.5 days post-coitus (dpc). At 6~9 dpc, pregnant mice were injected subcutaneously in the neck region with ZIKV (1x10^4 PFU in 200μL PBS). Various malformations were demonstrated in fetuses including smaller body sizes, reduced skull size, and defects in different body parts. Death or serious defects in the brain were also observed in some fetuses particularly when the ZIKV was injected in mice during early pregnancy (6~7 dpc). Unfortunately, no fetus was found with SBA-like malformation after being congenital challenged with ZIKV. As a continuation of this study, we will evaluate the therapeutic efficacy of PS18 against ZIKV-induced brain defects.
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