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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Stem Cells / cytology*
  • Adult Stem Cells / drug effects
  • Adult Stem Cells / metabolism
  • Animals
  • Animals, Newborn
  • Cell Count
  • Cell Proliferation
  • Growth and Development*
  • Interleukin-6 / blood
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Interleukin-6 / pharmacology*
  • Mice, Inbred C57BL
  • Neural Stem Cells / cytology*
  • Neural Stem Cells / drug effects
  • Neural Stem Cells / metabolism
  • Neurogenesis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Interleukin-6 / genetics
  • Receptors, Interleukin-6 / metabolism
  • Time Factors

Substances

  • Interleukin-6
  • RNA, Messenger
  • Receptors, Interleukin-6

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