| 研究実績の概要 |
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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