| 研究課題/領域番号 |
21K09324
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| 研究機関 | 大分大学 |
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研究代表者 |
カーン シャキル 大分大学, 医学部, 助教 (70746867)
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| 研究期間 (年度) |
2021-04-01 – 2024-03-31
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| キーワード | Spina Bifida Aperta / Chicken model / Mammalian model / Prosaposin / Neurotrophic factor / Therapeutic potentiality |
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| 研究実績の概要 |
Spina bifida aperta (SBA), a developmental disorder of the spinal cord, causes high pediatric mortality and is the leading cause of lifelong neurological complications including paralysis, orthopedic abnormalities, problems with bladder and bowel control, and painful complications. Current therapeutics for SBA have various limitations, including incomplete preservation of spinal tissue and the inability to rescue sensorimotor functions. We found that intra-amniotic delivery of prosaposin-derived 18 mer-peptide (PS18), a potential neurotrophic factor, to the chick embryo with SBA enhances the regeneration process and protects spinal tissue in developing spinal cord. Furthermore, treatment with PS18 dramatically improved the walking and bowel movement ability and reduce and painful complications of hatched chicks in postnatal life. The results are published as first author in a highly reputed scientific journal (Khan et al., iScience 2023; IF: 6.107).
In order to aim for clinical application of PS18, verification using not only the chicken model but also the mammalian SBA model is necessary. In this regard, we are trying to develop a mice model of SBA by inducing Zika virus which causes neural tube malformations and other birth defects. Zika virus solution (1x10^4 PFU in 200μL PBS) was administered subcutaneously to STAT1 KO mice on the 6th day of pregnancy to induce SBA and/or other defects in the fetus. Once a mice model with SBA or other neurological birth defects is developed, we will evaluate the therapeutic efficacy of PS18 with the aim of writing papers.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
Due to the effects of COVID-19 pandemic, the use of animal testing facilities and laboratories was restricted in earlier years. However, currently, the experiments are being conducted as planned.
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| 今後の研究の推進方策 |
In FY2023, we will proceed with the development of a mammalian SBA model by Zika virus infection or administration of retinoic acid. In the Zika virus infection-induced SBA model, Asian type of Zika virus is used in transgenic mice (STAT1 KO mice). Pregnant mice are given 1x10^4 PFU of Zika virus in 200μL PBS at embryonic day 6. In the SBA model with retinoic acid, retinoic acid (dissolved in olive oil) is administered orally at 60 mg/kg to pregnant animals when the embryo is 10 days old in the uterus of mice/rat.
Morphological, histological, and behavioral methods will be used to confirm the establishment of the SBA model. Congenital Zika virus infection has also been associated with other birth defects, including but not limited to brain atrophy and asymmetry, abnormally formed or absent brain structures, hydrocephalus, and neuronal migration disorders. Therefore, we will assess Zika virus infection-induced any of these birth defects in fetus. Next, we will assess the therapeutic efficacy of PS18 to treat SBA and other birth defects using these mammalian models.
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| 次年度使用額が生じた理由 |
Due to the effects of COVID-19 pandemic, the uses of animal testing facilities and laboratories were restricted last year resulting in an unused amount. In addition to the experimental plan for the next fiscal year, we intend to conduct experiments that were not feasible this year.
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