title: Diazoxide promotes oligodendrocyte differentiation in neonatal brain in normoxia and chronic sublethal hypoxia.
abstract: Periventricular white matter injury (PWMI) is the most common cause of brain injury in preterm infants. It is believed that loss of late oligodendrocyte progenitor cells (OPCs) and disrupted maturation of oligodendrocytes contributes to defective myelination in PWMI. At present, no clinically approved drugs are available for treating PWMI. Previously, we found that diazoxide promotes myelination and attenuates brain injury in the chronic sublethal hypoxia model of PWMI. In this study, we investigated the mechanisms by which diazoxide promotes myelination. We observed that diazoxide increases the ratio of differentiated oligodendrocytes in the cerebral white matter, promotes the expression of differentiation-associated transcriptional factors Nkx2.2 and Sox10, and increases the expression of myelin genes CNP and MBP. These results show that diazoxide promotes oligodendrocyte differentiation in the developing brain.
authors.affiliation: Department of Pediatrics, College of Medicine, University of Florida, Gainesville, FL 32610, United States.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Pediatrics, College of Medicine, University of Florida, Gainesville, FL 32610, United States.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Wendler
authors.affiliation: Department of Pediatrics, College of Medicine, University of Florida, Gainesville, FL 32610, United States.
authors.forename: Olivia
authors.initials: O
authors.lastname: Shi
authors.affiliation: Department of Pediatrics, College of Medicine, University of Florida, Gainesville, FL 32610, United States. Electronic address: srivkees@peds.ufl.edu.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Rivkees
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000378:metabolism; D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D001921:Brain / Q000166:cytology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D015687:Cell Hypoxia / Q000502:physiology*; D003981:Diazoxide / Q000494:pharmacology*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D000090322:Homeobox Protein Nkx-2.2; D000860:Hypoxia / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism; D000076104:Oligodendrocyte Transcription Factor 2; D009836:Oligodendroglia / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D051792:Basic Helix-Loop-Helix Proteins; D001973:Bromodeoxyuridine; D003981:Diazoxide; D000090322:Homeobox Protein Nkx-2.2; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D012333:RNA, Messenger; D014665:Vasodilator Agents; C000715627:Nkx2-2 protein, mouse; C512773:Olig2 protein, mouse
keywords: Diazoxide; Hypoxia; Mouse; Neonate; Oligodendrocyte; Periventricular white matter injury