The Secretome of Microglia Regulate Neural Stem Cell Function

Neuroscience. 2019 May 1:405:92-102. doi: 10.1016/j.neuroscience.2017.10.034. Epub 2017 Nov 1.

Abstract

Brain injury is associated with neuroinflammation, and microglia are key players in this process. Microglia can acquire pro-inflammatory or anti-inflammatory properties, but how this affects neural stem cells (NSCs) remains controversial. Here, NSCs were grown in conditioned media collected from either non-stimulated microglia, or microglia stimulated with pro- or anti-inflammatory agents. NSC survival, proliferation, migration, and differentiation were investigated thereafter. We found that NSCs kept in conditioned medium from the anti-inflammatory microglial subtype had better survival, increased migration, and lower astrocytic differentiation compared to NSCs grown in conditioned medium collected from the pro-inflammatory subtype. Finally, we found that NSCs differentiated in microglial conditioned media generated cells expressing the pro-inflammatory chemokine CCL2, most pronounced when differentiated in medium from the pro-inflammatory microglia subtype. Our results show that microglial subtypes regulate NSCs differently and induce generation of cells with inflammatory properties.

Keywords: M1; M2; Neurogenesis; Neuroinflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / cytology
  • Astrocytes / metabolism
  • Astrocytes / physiology
  • Cell Differentiation / drug effects
  • Cell Movement / drug effects
  • Culture Media, Conditioned
  • Cytokines / biosynthesis
  • Cytokines / metabolism*
  • Interleukin-4 / pharmacology
  • Lipopolysaccharides / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Microglia / cytology
  • Microglia / drug effects
  • Microglia / metabolism
  • Microglia / physiology*
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism
  • Neural Stem Cells / physiology*

Substances

  • Culture Media, Conditioned
  • Cytokines
  • Lipopolysaccharides
  • Interleukin-4