| First Author | Wu MD | Year | 2012 |
| Journal | Brain Behav Immun | Volume | 26 |
| Issue | 2 | Pages | 292-300 |
| PubMed ID | 21983279 | Mgi Jnum | J:234594 |
| Mgi Id | MGI:5790302 | Doi | 10.1016/j.bbi.2011.09.012 |
| Citation | Wu MD, et al. (2012) Adult murine hippocampal neurogenesis is inhibited by sustained IL-1beta and not rescued by voluntary running. Brain Behav Immun 26(2):292-300 |
| abstractText | 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-1beta (IL-1beta) is a pro-inflammatory cytokine that has been shown to acutely impair neurogenesis. To further investigate the relationship between sustained IL-1beta expression and adult neurogenesis, a mouse model with an IL-1beta excisionally activated transgene, IL-1beta(XAT), was utilized. Upon exposure to Cre recombinase, IL-1beta 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-1beta overexpression and rescued by voluntary running, which has been shown to enhance neurogenesis. Hippocampal inflammation in the IL-1beta(XAT) model severely impaired doublecortin (DCX) positive cells at 1 and 3 months after IL-1beta induction. Furthermore, BrdU labeling demonstrated a shift in cell lineage from neuronal to astroglial in the context of sustained hippocampal IL-1beta overexpression. Deletion of the IL-1 receptor prevented the decrease in DCX(+) cells. Voluntary running did not attenuate the effects of IL-1beta 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. |
