Adult murine hippocampal neurogenesis is inhibited by sustained IL-1β and not rescued by voluntary running

Michael D. Wu, Amy M. Hein, Michael J. Moravan, Solomon S. Shaftel, John A. Olschowka, M. Kerry O'Banion

Research output: Contribution to journalArticlepeer-review

95 Scopus citations

Abstract

Acute neuroinflammation reduces adult hippocampal neurogenesis but the role of chronic neuroinflammation, which may be more representative of ongoing processes in CNS disorders, remains relatively unknown. Interleukin-1β (IL-1β) is a pro-inflammatory cytokine that has been shown to acutely impair neurogenesis. To further investigate the relationship between sustained IL-1β expression and adult neurogenesis, a mouse model with an IL-1β excisionally activated transgene, IL-1β XAT, was utilized. Upon exposure to Cre recombinase, IL-1β overexpression in this model results in chronic neuroinflammation, which persists up to 12months and causes glial activation, cellular recruitment, and deficits in learning and memory. We hypothesized that adult neurogenesis would be reduced by sustained hippocampal IL-1β overexpression and rescued by voluntary running, which has been shown to enhance neurogenesis. Hippocampal inflammation in the IL-1β XAT model severely impaired doublecortin (DCX) positive cells at 1 and 3months after IL-1β induction. Furthermore, BrdU labeling demonstrated a shift in cell lineage from neuronal to astroglial in the context of sustained hippocampal IL-1β overexpression. Deletion of the IL-1 receptor prevented the decrease in DCX + cells. Voluntary running did not attenuate the effects of IL-1β expression demonstrated by DCX staining. These results suggest that chronic neuroinflammation severely impairs adult hippocampal neurogenesis and voluntary running is not beneficial as a therapy to rescue these effects.

Original languageEnglish
Pages (from-to)292-300
Number of pages9
JournalBrain, Behavior, and Immunity
Volume26
Issue number2
DOIs
StatePublished - Feb 2012

Keywords

  • Adult
  • Interleukin-1
  • Neurogenesis
  • Neuroinflammation
  • Running

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