Region specific oligodendrocyte transcription factor expression in a model of neonatal hypoxic injury
Autor: | Jonathan Chan, Bethann M. Affeldt, Andrea C. Pardo, Andre Obenaus |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
External capsule Oligodendrocyte Transcription Factor 2 Green Fluorescent Proteins Mice Transgenic Nerve Tissue Proteins White matter OLIG2 03 medical and health sciences Myelin Mice 0302 clinical medicine Developmental Neuroscience medicine Basic Helix-Loop-Helix Transcription Factors Animals Hypoxia biology Oligodendrocyte differentiation Age Factors Gene Expression Regulation Developmental Cell Differentiation White Matter Oligodendrocyte Myelin basic protein Cell biology Mice Inbred C57BL Disease Models Animal Oligodendroglia 030104 developmental biology medicine.anatomical_structure Homeobox Protein Nkx-2.2 Animals Newborn Hypoxia-Ischemia Brain biology.protein Neuroscience 030217 neurology & neurosurgery Myelin Proteins Developmental Biology Transcription Factors |
Zdroj: | International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience. 61 |
ISSN: | 1873-474X |
Popis: | White matter injury (WMI) of prematurity is associated with a spectrum of neurological disorders ranging from mild cognitive and behavioral deficits to cerebral palsy. Translational studies have implicated impaired oligodendrocyte development after hypoxia as the primary cause of WMI, but the underlying mechanisms remain poorly understood. The goal of this study was to identify alterations in the expression of oligodendrocyte precursor cell transcription factors in a mouse model of transient mild global hypoxia. Postnatal day (P) 7 mouse pups were exposed to hypoxia (7.5% O2) for 60minutes. We compared oligodendrocyte differentiation and subsequent myelin formation between hypoxia and sham animals at P9, P14 and P28 by examining the expression of key transcription factor regulators of oligodendrocyte differentiation (Ascl1, Olig1, Olig2, and Nkx2.2), as well as APC, a mature oligodendrocyte marker, in the major white matter regions including the corpus callosum, external capsule and anterior commissure. We also examined the effect on myelin formation by examining two myelin specific protein constituents, myelin associated glycoprotein (MAG) and myelin basic protein (MBP), in white matter tracts and whole brain lysate respectively. We found that transient hypoxia at P7 altered the expression of Ascl1, Olig1 and Nkx2.2, resulting in delayed myelination in the external capsule. In addition, our study showed that oligodendrocyte progenitor cells specified several days prior to a hypoxic event are more susceptible to maturation arrest than those specified shortly prior to hypoxia. Our results suggest that alterations of Ascl1, Olig1 and Nkx2.2 underlie impaired oligodendrocyte differentiation and deficient myelination in WMI. These transcription factors are potential therapeutic targets for the treatment of WMI in preterm infants. |
Databáze: | OpenAIRE |
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