Glutathione peroxidase overexpression does not rescue impaired neurogenesis in the injured immature brain

Matthew B. Potts, Radoslaw Rola, Catherine P. Claus, Donna M. Ferriero, John R. Fike, Linda J. Noble-Haeusslein*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Traumatic brain injury (TBI) is a leading cause of disability among young children and is associated with long-term cognitive deficits. These clinical findings have prompted an investigation of the hippocampus in an experimental model of trauma to the developing brain at postnatal day (p21). Previous studies using this model have revealed a progressive loss of neurons in the hippocampus as brain-injured animals mature to young adulthood. Here we determined whether this hippocampal vulnerability is likewise reflected in altered neurogenesis and whether the antioxidant glutathione peroxidase (GPx) modulates neurogenesis during maturation of the injured immature brain. Male transgenic mice that overexpress GPx and wild-type littermates were subjected to controlled cortical impact or sham surgery on p21. At 2 weeks postinjury, the numbers of proliferating cells and immature neurons within the subgranular zone were measured by using Ki-67 and doublecortin, respectively. Bromodeoxyuridine (BrdU) was used to label dividing cells beginning 2 weeks postinjury. Survival (BrdU+) and neuronal differentiation (BrdU+/NeuN+) were then measured 4 weeks later via confocal microscopy. Two-way ANOVA revealed no significant interaction between genotype and injury. Subsequent analysis of the individual effects of injury and genotype, however, showed a significant reduction in subgranular zone proliferation (Ki-67) at 2 weeks postinjury (P = 0.0003) and precursor cell survival (BrdU+) at 6 weeks postinjury (P = 0.016) and a trend toward reduced neuronal differentiation (BrdU+/NeuN+) at 6 weeks postinjury (P = 0.087). Overall, these data demonstrate that traumatic injury to the injured immature brain impairs neurogenesis during maturation and suggest that GPx cannot rescue this reduced neurogenesis.

Original languageEnglish (US)
Pages (from-to)1848-1857
Number of pages10
JournalJournal of Neuroscience Research
Volume87
Issue number8
DOIs
StatePublished - 2009

Keywords

  • Dentate gyrus
  • Glutathione peroxidase
  • Hippocampus
  • Traumatic brain injury

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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