Related Experiment Video
Updated: Dec 9, 2025
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Single-cell mass cytometry of microglia in major depressive disorder reveals a non-inflammatory phenotype with
Chotima Böttcher1, Camila Fernández-Zapata2, Gijsje J L Snijders3
1Department of Neuropsychiatry and Laboratory of Molecular Psychiatry, Charité - Universitätsmedizin Berlin, Berlin, Germany. chotima.boettcher@charite.de.
Abstract:
Stress-induced disturbances of brain homeostasis and neuroinflammation have been implicated in the pathophysiology of mood disorders. In major depressive disorder (MDD), elevated levels of proinflammatory cytokines and chemokines can be found in peripheral blood, but very little is known about the changes that occur directly in the brain. Microglia are the primary immune effector cells of the central nervous system and exquisitely sensitive to changes in the brain microenvironment. Here, we performed the first single-cell analysis of microglia from four different post-mortem brain regions (frontal lobe, temporal lobe, thalamus, and subventricular zone) of medicated individuals with MDD compared to controls. We found no evidence for the induction of inflammation-associated molecules, such as CD11b, CD45, CCL2, IL-1β, IL-6, TNF, MIP-1β (CCL4), IL-10, and even decreased expression of HLA-DR and CD68 in microglia from MDD cases. In contrast, we detected increased levels of the homeostatic proteins P2Y12 receptor, TMEM119 and CCR5 (CD195) in microglia from all brain regions of individuals with MDD. We also identified enrichment of non-inflammatory CD206hi macrophages in the brains of MDD cases. In sum, our results suggest enhanced homeostatic functions of microglia in MDD.
Insights
Major depressive disorder (MDD) microglia show enhanced homeostatic functions, not inflammation. This study analyzed single-cell microglia from MDD brains, revealing increased homeostatic proteins and non-inflammatory macrophages.
Area of Science:
- Neuroscience
- Immunology
- Psychiatry
Background:
- Stress and neuroinflammation are linked to mood disorders like major depressive disorder (MDD).
- Peripheral inflammation markers are known in MDD, but brain-specific changes, especially in microglia, are poorly understood.
- Microglia are central nervous system immune cells sensitive to brain microenvironment shifts.
Purpose of the Study:
- To investigate microglial changes in the brain of individuals with MDD using single-cell analysis.
- To determine if inflammation-associated molecules or homeostatic proteins are altered in MDD microglia.
- To identify potential non-inflammatory macrophage populations in the MDD brain.
Main Methods:
- Performed single-cell analysis on post-mortem brain tissue from four regions (frontal lobe, temporal lobe, thalamus, subventricular zone).
- Compared microglia from medicated individuals with MDD to control subjects.
- Quantified expression levels of inflammation-associated molecules (e.g., CD11b, TNF) and homeostatic proteins (e.g., P2Y12, TMEM119).
Main Results:
- No evidence of increased inflammation markers (e.g., CCL2, IL-6, TNF) was found in MDD microglia; some, like HLA-DR and CD68, were decreased.
- Significantly increased levels of homeostatic proteins, including P2Y12 receptor, TMEM119, and CCR5, were detected in microglia from all analyzed brain regions in MDD cases.
- An enrichment of non-inflammatory CD206high macrophages was observed in the brains of individuals with MDD.
Conclusions:
- The findings suggest an enhancement of homeostatic functions in microglia from individuals with MDD, rather than a pro-inflammatory state.
- These results challenge the traditional view of neuroinflammation in MDD pathophysiology and highlight the complexity of microglial responses.
- Further research is needed to elucidate the functional implications of enhanced microglial homeostasis in MDD.
