Related Experiment Video
Updated: Apr 24, 2026

Selective Depletion of Microglia from Cerebellar Granule Cell Cultures Using L-leucine Methyl Ester
Published on: July 7, 2015
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.
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.
Abstract:
Evidence indicates that widely prescribed mood stabilizer, lithium (Li), mediates cellular functions of differentiated monocytic cells, including microglial migration, monocyte-derived dendritic cell (MoDC) differentiation, and amelioration of monocytic malfunctions observed in neuropsychiatric diseases. Here, we surveyed molecules which take major roles in regulating these monocytic cellular functions. MoDCs treated with 1 and 5 mM Li, and microglia separated from Li-treated mice were subjected to microarray-based comprehensive gene expression analyses. Findings were validated using multiple experiments, including quantitative PCR, ELISA and immunostaining studies. Differing effects of Li on the two cell types were observed. Inflammation- and chemotaxis-relevant genes were significantly over-represented among Li-induced genes in MoDCs, whereas no specific category of genes was over-represented in microglia. The third component of complement (C3) was the only gene which was significantly induced by a therapeutic concentration of Li in both MoDCs and microglia. C3 production was increased by Li via GSK-3 inhibition. Li-induced C3 production was seen only in differentiated monocytic cells, but not in circulating monocytes. Our findings highlight a link between Li treatment and C3 production in differentiated monocytic cells, and reveal a regulatory role of GSK-3 in C3 production. Induction of microglial C3 production might be a novel neuroprotective mechanism of Li via regulating interactions between microglia and neurons. GLIA 2015;63:257-270.
More Related Videos
Related Concept Videos
Mania and Antimanic Drugs: Overview
Ligand-Gated Ion Channel Receptor: Gating Mechanism
Long-term Depression
Calcium Ion Concentration Mechanism
If over...

