Therapeutic concentration of lithium stimulates complement C3 production in dendritic cells and microglia via GSK-3

Zhiqian Yu1, Chiaki Ono, Setsuya Aiba

  • 1Department of Disaster Psychiatry, International Research Institute for Disaster Science, Tohoku University, Sendai, Japan; Department of Biological Psychiatry, Graduate School of Medicine, Tohoku University, Sendai, Japan; Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.

Glia
|September 3, 2014
PubMed

Insights

Lithium (Li) treatment increases complement C3 production in differentiated monocytic cells, including microglia, by inhibiting GSK-3. This suggests a novel neuroprotective role for lithium in neuropsychiatric diseases.

Area of Science:

  • Neuroscience
  • Immunology
  • Pharmacology

Background:

  • Lithium (Li) is a mood stabilizer influencing monocytic cell functions relevant to neuropsychiatric disorders.
  • Key cellular processes affected include microglial migration and monocyte-derived dendritic cell (MoDC) differentiation.

Purpose of the Study:

  • To identify molecules regulating Li-mediated monocytic cellular functions.
  • To investigate the differential effects of Li on MoDCs and microglia.

Main Methods:

  • Microarray-based gene expression analysis of Li-treated MoDCs and microglia.
  • Validation using quantitative PCR, ELISA, and immunostaining.
  • Assessment of GSK-3 inhibition's role in Li-induced C3 production.

Main Results:

  • Li differentially affected gene expression in MoDCs and microglia.
  • Inflammation- and chemotaxis-related genes were upregulated in Li-treated MoDCs.
  • Complement C3 was the sole gene significantly induced by Li in both cell types.
  • Li-induced C3 production occurred via GSK-3 inhibition and was specific to differentiated cells.

Conclusions:

  • Lithium treatment links to increased C3 production in differentiated monocytic cells.
  • GSK-3 plays a regulatory role in C3 production.
  • Microglial C3 induction by Li may represent a novel neuroprotective mechanism.

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