title: Adult murine hippocampal neurogenesis is inhibited by sustained IL-1β and not rescued by voluntary running.
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 12 months 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 3 months 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.
authors: Department of Neurobiology and Anatomy, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
authors: Michael D
authors: MD
authors: Wu
authors: Amy M
authors: AM
authors: Hein
authors: Michael J
authors: MJ
authors: Moravan
authors: Solomon S
authors: SS
authors: Shaftel
authors: John A
authors: JA
authors: Olschowka
authors: M Kerry
authors: MK
authors: O'Banion
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects; D000089662:Doublecortin Protein; D005260:Female; D006624:Hippocampus / Q000033:anatomy & histology / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D007249:Inflammation / Q000139:chemically induced; D007276:Injections, Intraventricular; D053583:Interleukin-1beta / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D055495:Neurogenesis / Q000187:drug effects* / Q000502:physiology; D005082:Physical Exertion / Q000276:immunology / Q000502:physiology*
chemical_list: C000714847:Dcx protein, mouse; D000089662:Doublecortin Protein; D053583:Interleukin-1beta