title: Exogenous Oct4 in combination with valproic acid increased neural progenitor markers: an approach for enhancing the repair potential of the brain.
abstract: OBJECTIVE
  Attempts are aimed to introduce new approaches toward enhancing the brain's potential for repair in neurodegenerative diseases and traumatic injuries. Here we report an increased expression of pluripotency and progenitor markers within the brain following pretreatment with valproic acid (VPA) and in vivo transfection of inducible Oct4-expressing viral particles.
  
  
  METHODS
  Systemic administration of VPA was performed for one week prior to an intracerebroventricular injection of the Oct4-expressing vector into the right side of the brain. Oct4 expression was induced by doxycycline from day 1 post-transfection for an additional week. Real time-PCR and immunohistofluorescence were used for evaluation of marker expression.
  
  
  RESULTS
  Real time-PCR analyses of samples collected from the area of transfection within the injected-lateral ventricle revealed increased expression of some stem cell and progenitor markers, which included endogenous Oct4, Nanog, Klf4, c-Myc, Pax6 and Sox1. Expressions of Oct4, SSEA1 and Nanog were further confirmed by immunohistofluorescence. The increased neural progenitor and pluripotency markers due to Oct4 overexpression did not lead to teratoma formation during a 100day follow-up.
  
  
  CONCLUSIONS
  Our findings suggest that the application of Oct4 as a reprogramming factor in conjunction with VPA, an epigenetic modifier, might be a potential strategy for increasing the brain's capability to repair itself.
authors.affiliation: Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Samaneh
authors.initials: S
authors.lastname: Dehghan
authors.affiliation: Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Sareh
authors.initials: S
authors.lastname: Asadi
authors.affiliation: Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Hajikaram
authors.affiliation: Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Masoud
authors.initials: M
authors.lastname: Soleimani
authors.affiliation: Department of Molecular Genetics, Faculty of Basic Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Seyed Javad
authors.initials: SJ
authors.lastname: Mowla
authors.affiliation: Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Yaghoub
authors.initials: Y
authors.lastname: Fathollahi
authors.affiliation: Neuroscience Research Center, Shahid Beheshti Medical University, Tehran, Iran.
authors.forename: Abolhassan
authors.initials: A
authors.lastname: Ahmadiani
authors.affiliation: Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran; Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran. Electronic address: mjavan@modares.ac.ir.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Javan
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism*; D015153:Blotting, Western; D001921:Brain / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D003131:Combined Modality Therapy; D007124:Immunoenzyme Techniques; D000090062:Kruppel-Like Factor 4; D051379:Mice; D008810:Mice, Inbred C57BL; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013724:Teratoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: D000927:Anticonvulsants; D015415:Biomarkers; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D012333:RNA, Messenger; D014635:Valproic Acid
keywords: Endogenous neural progenitors; Oct4; Reprogramming factors; Valproic acid