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Updated: May 15, 2026
Quantification of Microglial Engulfment of Synaptic Material Using Flow Cytometry
Published on: May 31, 2024
Microglia: new roles for the synaptic stripper
Helmut Kettenmann1, Frank Kirchhoff, Alexei Verkhratsky
1Max-Delbrück Center for Molecular Medicine, 13125 Berlin, Germany. kettenmann@mdc-berlin.de
Abstract:
Any pathologic event in the brain leads to the activation of microglia, the immunocompetent cells of the central nervous system. In recent decades diverse molecular pathways have been identified by which microglial activation is controlled and by which the activated microglia affects neurons. In the normal brain microglia were considered "resting," but it has recently become evident that they constantly scan the brain environment and contact synapses. Activated microglia can remove damaged cells as well as dysfunctional synapses, a process termed "synaptic stripping." Here we summarize evidence that molecular pathways characterized in pathology are also utilized by microglia in the normal and developing brain to influence synaptic development and connectivity, and therefore should become targets of future research. Microglial dysfunction results in behavioral deficits, indicating that microglia are essential for proper brain function. This defines a new role for microglia beyond being a mere pathologic sensor.
Insights
Microglia, the brain's immune cells, are crucial for normal brain function, not just in disease. They actively shape synaptic development and connectivity throughout life.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia are the primary immune cells of the central nervous system.
- Traditionally viewed as passive responders to pathology, recent evidence suggests continuous microglial activity in the healthy brain.
- Microglial roles in synaptic pruning and development are increasingly recognized.
Purpose of the Study:
- To review evidence for microglial involvement in normal synaptic development and connectivity.
- To highlight molecular pathways used by microglia in both health and disease.
- To propose microglia as a therapeutic target for brain disorders.
Main Methods:
- Literature review and synthesis of existing research on microglial function.
- Analysis of molecular pathways controlling microglial activation and their impact on neurons.
- Examination of studies on microglial roles in brain development and pathology.
Main Results:
- Microglia constantly interact with synapses, not just during disease.
- Pathology-associated molecular pathways are also active in normal microglial function.
- Microglial dysfunction leads to significant behavioral deficits.
Conclusions:
- Microglia play an active and essential role in maintaining proper brain function.
- Their influence extends to synaptic development and connectivity, challenging the "resting" paradigm.
- Targeting microglial pathways offers potential for novel therapeutic strategies.
