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Dynamic motility of microglia: purinergic modulation of microglial movement in the normal and pathological brain
Keiko Ohsawa1, Shinichi Kohsaka
1Department of Neurochemistry, National Institute of Neuroscience, Tokyo, Japan.
Abstract:
Microglia have highly branched and motile cell processes and constantly screen the brain parenchyma under physiological conditions. In response to pathological stimuli, microglia exhibit morphological changes and migrate toward the lesioned site, where they play important roles in inflammatory reactions and neuronal damage. Within minutes of brain damage, microglial processes rapidly extend toward the injured site. The chemoattractive response is triggered by ATP released at the site of injury and the consequent activation of the purinergic receptor P2Y₁₂R on microglia. In addition to the purinergic signals, various neuronal signaling molecules actively and negatively control microglial motility, which is important for regulating the functional activation of microglia in response to pathology. In this review, we focus on the dynamic motion of microglia and describe several key molecules regulating microglial motility in normal and pathological brain tissues.
Insights
Microglia rapidly extend processes toward brain injury sites, guided by ATP and purinergic receptors. Neuronal signals also regulate this crucial microglial motility for brain pathology response.
Area of Science:
- Neuroscience
- Cell Biology
- Immunology
Background:
- Microglia, the brain's resident immune cells, possess dynamic, motile processes essential for surveillance under physiological conditions.
- Upon brain injury, microglia undergo morphological changes and migrate to the lesion site, participating in inflammation and neuronal damage.
- Rapid microglial process extension towards injury sites occurs within minutes, crucial for initiating the response.
Purpose of the Study:
- To review the dynamic motion of microglia in the brain.
- To describe key molecules that regulate microglial motility in both normal and pathological conditions.
- To highlight the role of chemoattraction and neuronal signaling in microglial behavior.
Main Methods:
- Literature review focusing on microglial dynamics and molecular regulation.
- Analysis of signaling pathways involved in microglial chemoattraction.
- Examination of factors controlling microglial motility in neuropathology.
Main Results:
- Adenosine triphosphate (ATP) released at injury sites triggers microglial chemoattraction via the P2Y₁₂R purinergic receptor.
- Microglial process extension towards damaged areas is a rapid, early response to brain injury.
- Neuronal signaling molecules play a significant role in negatively controlling microglial motility, fine-tuning their activation state.
Conclusions:
- Microglial motility is a tightly regulated process involving both attractive (e.g., ATP) and repulsive (neuronal signals) cues.
- Understanding these regulatory mechanisms is key to comprehending microglial roles in brain health and disease.
- Targeting microglial motility could offer therapeutic strategies for neurological disorders.
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