Conditional overexpression of insulin-like growth factor-1 enhances hippocampal neurogenesis and restores immature neuron dendritic processes after traumatic brain injury

Shaun W. Carlson, Sindhu K. Madathil, Diana M. Sama, Xiang Gao, Jinhui Chen, Kathryn E. Saatman

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Traumatic brain injury (TBI) is associated with neuronal damage or neuronal death in the hippocampus, a region critical for cognitive function. Immature neurons within the hippocampal neurogenic niche are particularly susceptible to TBI. Therapeutic strategies that protect immature hippocampal neurons or enhance posttraumatic neurogenesis may be advantageous for promoting functional recovery after TBI. Insulin-like growth factor-1 (IGF-1) promotes neurogenesis in the adult brain, but its effects on neurogenesis after TBI are unknown. We used an astrocyte-specific conditional IGF-1-overexpressing mouse model to supplement IGF-1 in regions of neuronal damage and reactive astrocytosis after controlled cortical impact injury. Although early loss of immature neurons was not significantly attenuated, overexpression of IGF-1 resulted in a marked increase in immature neuron density in the subgranular zone at 10 days after injury. This delayed increase seemed to be driven by enhanced neuron differentiation rather than by increased cellular proliferation. In wild-type mice, dendrites of immature neurons exhibited significant decreases in total length and number of bifurcations at 10 days after injury versus neurons in sham-injured mice. In contrast, the morphology of immature neuron dendrites in brain-injured IGF-1-overexpressing mice was equivalent to that in sham controls. These data provide compelling evidence that IGF-1 promotes neurogenesis after TBI.

Original languageEnglish (US)
Pages (from-to)734-746
Number of pages13
JournalJournal of Neuropathology and Experimental Neurology
Volume73
Issue number8
DOIs
StatePublished - Aug 2014

Keywords

  • Cellular proliferation
  • Controlled cortical impact
  • Dendrites
  • Doublecortin
  • Hippocampus
  • IGF-1
  • Neuronal differentiation
  • Traumatic brain injury

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Neurology
  • Cellular and Molecular Neuroscience

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