The Function of Microglia, Either Neuroprotection or Neurotoxicity, Is Determined by the Equilibrium Among Factors Released From Activated Microglia in Vitro

Brain Res. 2007 Jul 23;1159:8-17. doi: 10.1016/j.brainres.2007.04.066. Epub 2007 May 3.

Abstract

Opposing functions of activated microglia, namely neuroprotection or neurotrophy versus neurodestruction or neurotoxicity, have been observed in a number of experimental models of neurotrauma and neurodegenerative diseases. However, the mechanism(s) involved in the determination of which function activated microglia execute under a given set of conditions still remains to be elucidated. Our current in vitro study has revealed that a neuroprotective/neurotrophic or a neurodestructive/neurotoxic microglial function may be configured by the equilibrium among various microglial factors released into the microenvironment. When NSC-34 neurons were treated with lower concentrations of lipopolysaccharide-stimulated BV-2 microglial conditioned medium (LPS-BVCM), viability of the NSC-34 neurons increased, outgrowth of neuronal processes was promoted, and the formation of 2,5-hexanedione-induced aggregates was prevented. However, when NSC-34 neurons were treated with higher concentrations of the same LPS-BVCM, neuronal viability was reduced, apoptosis was induced and outgrowth of neuronal processes was prevented. Measurement of the cytokines tumor necrotic factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and IL-6 in the LPS-BVCM has shown that the upregulation in expression for each cytokine varied both temporally and quantitatively. It is postulated that an alteration in the concentration of the LPS-BVCM might significantly affect the functional balance of microglial factors in the microenvironment with a resultant different microglial function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Annexin A5 / metabolism
  • Apoptosis / drug effects
  • Cell Enlargement
  • Cell Growth Processes / drug effects
  • Cell Line
  • Cell Survival / drug effects
  • Culture Media, Conditioned / pharmacology
  • Cytokines / metabolism
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Enzyme-Linked Immunosorbent Assay / methods
  • Glycols / pharmacology
  • Hybridomas
  • Lipopolysaccharides / pharmacology
  • Mice
  • Microglia / chemistry*
  • Microglia / drug effects
  • Microglia / physiology*
  • Neurites / drug effects
  • Neurites / physiology
  • Time Factors

Substances

  • Annexin A5
  • Culture Media, Conditioned
  • Cytokines
  • Glycols
  • Lipopolysaccharides
  • 2,5-hexanediol