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Drug Development and Neuroprotection

開催日 2014/9/11
時間 9:00 - 10:00
会場 Room J(313+314)
Chairperson(s) 池田 華子 / Hanako Ohashi-Ikeda (京都大学医学部附属病院 臨床研究総合センター / Institute for Advancement of Clinical and Translational Science, Kyoto University Hospital, Japan)
東田 千尋 / Chihiro Tohda (富山大学和漢医薬学総合研究所神経機能学分野 / Division of Neuromedical Science, Institute of Natural Medicine, University of Toyama, Japan)

Enhancing brain repair potential in kainic acid-degenerated hippocampus by pluripotency inducers

  • O1-J-1-4
  • Sareh Asadi:1 Samaneh Dehghan:1 Mohammad Javan:1 
  • 1:Tarbiat Modares University, Iran 

Introduction: The mammalian adult brain has a limited potential for repair. Attempts are aimed to introduce new approaches toward enhancing the brain's repair potential in neurodegenerative diseases and traumatic brain injuries. Here we have reported increased neurogenesis in the hippocampal CA3 area of mice suffering from kainic acid (KA) induced neurodegeneration after treatment with valproic acid (VPA) and in vivo transfection with Oct4 expressing viral particles. Methods: Dox-inducible Oct4 expressing viral particles and pluripotency inducers such as BIX01294, Bayk8644 and RG-108 were injected i.c.v and VPA was systematic administered via oral gavages. After one or two weeks, induction of pluripotency (Oct4, Klf4, Nanog, c-Myc and Sox2) and neural stem markers (Pax6 and Sox1) were measured using RT-PCR. For further analysis, Oct4, Nanog and SSEA1 expression is also studied by immunohistofluerescence. To induce neurodegeneration on both sides of the CA3 area of the hippocampus, KA was applied intranasally. Histological analysis was used to study neurogenesis within the brain. PSA-NCAM and Nestin as neuroblast markers were also studied by immuneflurescent. Results: Real time-PCR analysis of samples collected from the rims of the injected-lateral ventricle revealed increased expression of some pluripotency and neural stem markers, included endogenous Oct4 (P<0.001), Nanog (P<0.001), Klf4 (P<0.001), c-Myc (P<0.001), Pax6 (P<0. 01) and Sox1(P<0. 01) after VPA pre-treatment and Oct4 exogenous expression. Expressions of Oct4, SSEA1 and Nanog were after this treatment further confirmed by immunohistofluorescence. Animals which treated by VPA pre-treatment and Oct4 exogenous expression before inducing neurodegeneration in their hippocampus showed more neuron number in their Oct4 injected side of the brain comparing to degenerated hippocampus in control group. Moreover, significant improvement in neurogenesis and increased neuroblast markers were seen in injected brain side. Conclusion: Our findings suggested that VPA pre-treatment in conjunction with Oct4 exogenous expression can induce pluripotency and neural stem markers in vivo and enhance the brain's potential to repair the KA-degenerated hippocampus.

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