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A Novel In Vitro Live-imaging Assay of Astrocyte-mediated Phagocytosis Using pH Indicator-conjugated Synaptosomes
Published on: February 5, 2018
Molecular mechanisms underlying microglial sensing and phagocytosis in synaptic pruning
Anran Huo1, Jiali Wang1, Qi Li1
1Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University; Institute of Neuroscience and Jiangsu Key Laboratory of Neuropsychiatric Diseases, Soochow University, Suzhou, Jiangsu Province, China.
Abstract:
Microglia are the main non-neuronal cells in the central nervous system that have important roles in brain development and functional connectivity of neural circuits. In brain physiology, highly dynamic microglial processes are facilitated to sense the surrounding environment and stimuli. Once the brain switches its functional states, microglia are recruited to specific sites to exert their immune functions, including the release of cytokines and phagocytosis of cellular debris. The crosstalk of microglia between neurons, neural stem cells, endothelial cells, oligodendrocytes, and astrocytes contributes to their functions in synapse pruning, neurogenesis, vascularization, myelination, and blood-brain barrier permeability. In this review, we highlight the neuron-derived "find-me," "eat-me," and "don't eat-me" molecular signals that drive microglia in response to changes in neuronal activity for synapse refinement during brain development. This review reveals the molecular mechanism of neuron-microglia interaction in synaptic pruning and presents novel ideas for the synaptic pruning of microglia in disease, thereby providing important clues for discovery of target drugs and development of nervous system disease treatment methods targeting synaptic dysfunction.
Insights
Microglia, the brain's immune cells, refine neural circuits by responding to neuron signals for synapse pruning. This interaction is crucial for brain development and offers new therapeutic targets for nervous system diseases.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia are key non-neuronal cells in the central nervous system.
- They play vital roles in brain development and neural circuit function.
- Microglia dynamically interact with various brain cells, influencing synaptic pruning, neurogenesis, and more.
Purpose of the Study:
- To review neuron-derived molecular signals that guide microglial synapse pruning.
- To elucidate the molecular mechanisms of neuron-microglia interactions in synaptic pruning.
- To explore the role of microglial synaptic pruning in disease and potential therapeutic strategies.
Main Methods:
- Literature review focusing on neuron-microglia signaling.
- Analysis of molecular mechanisms underlying synaptic pruning.
- Discussion of implications for nervous system disease treatment.
Main Results:
- Neuron-derived "find-me," "eat-me," and "don't eat-me" signals direct microglial activity.
- These signals are critical for synapse refinement during brain development.
- Understanding these interactions provides insights into synaptic dysfunction in disease.
Conclusions:
- Microglia are essential for synaptic pruning, guided by specific molecular cues from neurons.
- Dysfunctional microglial synaptic pruning is implicated in nervous system disorders.
- Targeting neuron-microglia communication offers potential therapeutic avenues for neurological diseases.

