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Stem Cell Reports. 2018 May 8;10(5):1464-1480. doi: 10.1016/j.stemcr.2018.03.008. Epub 2018 Apr 5.

Interleukin-6 Regulates Adult Neural Stem Cell Numbers during Normal and Abnormal Post-natal Development.

Author information

1
Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto M5G 1L7, Canada.
2
Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto M5G 1L7, Canada; Institute of Medical Science, University of Toronto, Toronto M5G 1A8, Canada.
3
Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto M5G 1L7, Canada; Department of Molecular Genetics, University of Toronto, Toronto M5G 1A8, Canada.
4
Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto M5G 1L7, Canada; Institute of Medical Science, University of Toronto, Toronto M5G 1A8, Canada; Department of Molecular Genetics, University of Toronto, Toronto M5G 1A8, Canada. Electronic address: dkaplan@sickkids.ca.
5
Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto M5G 1L7, Canada; Institute of Medical Science, University of Toronto, Toronto M5G 1A8, Canada; Department of Molecular Genetics, University of Toronto, Toronto M5G 1A8, Canada; Department of Physiology, University of Toronto, Toronto M5G 1A8, Canada. Electronic address: fredam@sickkids.ca.

Abstract

Circulating systemic factors can regulate adult neural stem cell (NSC) biology, but the identity of these circulating cues is still being defined. Here, we have focused on the cytokine interleukin-6 (IL-6), since increased circulating levels of IL-6 are associated with neural pathologies such as autism and bipolar disorder. We show that IL-6 promotes proliferation of post-natal murine forebrain NSCs and that, when the IL-6 receptor is inducibly knocked out in post-natal or adult neural precursors, this causes a long-term decrease in forebrain NSCs. Moreover, a transient circulating surge of IL-6 in perinatal or adult mice causes an acute increase in neural precursor proliferation followed by long-term depletion of adult NSC pools. Thus, IL-6 signaling is both necessary and sufficient for adult NSC self-renewal, and acute perturbations in circulating IL-6, as observed in many pathological situations, have long-lasting effects on the size of adult NSC pools.

KEYWORDS:

CNS cytokines; adult neurogenesis; circulating stem cell factors; interleukin-6; neural stem cell; neural stem cell niche; olfactory bulb; postnatal brain development; stem cell depletion

PMID:
29628394
PMCID:
PMC5995693
DOI:
10.1016/j.stemcr.2018.03.008
[Indexed for MEDLINE]
Free PMC Article

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