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Updated: Aug 4, 2026
Preparation of Primary Mixed Glial Cultures from Adult Mouse Spinal Cord Tissue
Published on: November 19, 2016
Histamine production by cultured microglial cells of the mouse
1Department of Medical Physics, School of Allied Health Sciences, Faculty of Medicine, Osaka University, 1-7 Yamadaoka, Suita, 565-0871, Osaka, Japan.
Abstract:
We previously reported that cells other than mast cells or neurons could synthesize histamine in response to lipopolysaccharide (LPS) or interleukin 1beta in the rat brain. To identify the responsible cells, we examined histidine decarboxylase (HDC) activity and the expression of HDC mRNA in GMI 6-3 mouse microglial cells. Both the activity and mRNA for HDC in GMI 6-3 cells were induced by LPS treatment, and the induction was sensitive to calmodulin-dependent kinase II inhibitor, KN62. These findings indicate that microglia is a third cell type producing histamine in the brain.
Insights
Microglia, a type of immune cell in the brain, can produce histamine. This discovery identifies microglia as a third cell type, alongside mast cells and neurons, capable of histamine synthesis in the brain.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Histamine synthesis in the brain was previously attributed to mast cells and neurons.
- Recent findings suggest other cell types may also produce histamine in response to inflammatory stimuli like lipopolysaccharide (LPS) and interleukin-1beta.
- Identifying these additional histamine-producing cells is crucial for understanding neuroinflammation and brain function.
Purpose of the Study:
- To identify the specific cell type responsible for non-neuronal, non-mast cell histamine synthesis in the brain.
- To investigate the role of microglia in histamine production.
- To elucidate the molecular mechanisms regulating histamine synthesis in these cells.
Main Methods:
- Examined histidine decarboxylase (HDC) activity in GMI 6-3 mouse microglial cells.
- Assessed the expression of HDC mRNA in response to lipopolysaccharide (LPS) stimulation.
- Investigated the effect of the calmodulin-dependent kinase II inhibitor, KN62, on HDC induction.
Main Results:
- Lipopolysaccharide (LPS) treatment significantly induced both histidine decarboxylase (HDC) activity and HDC mRNA expression in GMI 6-3 microglial cells.
- The induction of HDC in microglia was sensitive to inhibition by KN62, a calmodulin-dependent kinase II inhibitor.
- These results demonstrate that microglia possess the enzymatic machinery to synthesize histamine.
Conclusions:
- Microglia represent a third distinct cell type in the brain capable of synthesizing histamine.
- Histamine production by microglia is regulated by inflammatory signals and intracellular signaling pathways involving calmodulin-dependent kinase II.
- This finding has significant implications for understanding the role of histamine in neuroinflammation and brain signaling.
