title: Age-related changes in the oligodendrocyte progenitor pool influence brain remodeling after injury.
abstract: Brain remodeling occurs after all forms of brain injury, though the mechanisms underlying this phenomenon are mostly unknown. Neural stem and progenitor cells are one source of endogenous cells that may contribute to brain remodeling and subsequent recovery. In addition, certain populations of progenitors are particularly susceptible to injury, and their depletion may lead to the impairment of developmental processes that vary with age. We particularly focus on glial progenitors, which are more abundant postnatally and particularly susceptible to acquired brain injuries such as traumatic brain injury. We have recently characterized a novel transgenic mouse that expresses herpes thymidine kinase under the control of the neural-progenitor-specific nestin promoter and allows for temporally induced ablation of dividing progenitors. By genetically depleting dividing cortical progenitors at various times, we identify postnatal day 7 (P7) to P14 as a critical period for oligodendrogenesis. Targeted ablation of dividing progenitors during this window leads to cell-specific depletion of oligodendrocyte precursors expressing platelet-derived growth factor receptor-α and corresponding myelination and motor deficits. This modeling provides insight into how the age at which white matter injury occurs influences both injury severity and subsequent recovery.
authors.affiliation: Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Jamie
authors.initials: J
authors.lastname: Wright
authors.forename: Gui
authors.initials: G
authors.lastname: Zhang
authors.forename: Tzong-Shiue
authors.initials: TS
authors.lastname: Yu
authors.forename: Steven G
authors.initials: SG
authors.lastname: Kernie
mesh_terms: D000367:Age Factors; D000818:Animals; D015153:Blotting, Western; D001930:Brain Injuries / Q000473:pathology*; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D009836:Oligodendroglia / Q000473:pathology*; D013234:Stem Cells / Q000473:pathology*