Microglia morphology in the physiological and diseased brain - from fixed tissue to in vivo conditions

Area of Science:

• Neuroscience
• Immunology
• Cell Biology

Background:

• Microglia, the primary immune cells of the central nervous system (CNS), have been implicated in numerous CNS pathologies for nearly a century.
• Historically, microglia's immune status was inferred from their morphology, but recent findings reveal their dynamic nature and rapid in vivo responses.
• The term 'resting' microglia is being supplanted by 'surveilling' microglia to reflect their active monitoring role.

Purpose of the Study:

• To highlight the dynamic nature of microglia and their rapid responses within the central nervous system.
• To address the challenges in classifying microglia based solely on morphology due to tissue processing artifacts.
• To underscore the implications of microglia's dynamic behavior for therapeutic strategies in brain diseases.

Main Methods:

• Review of recent neuroresearch findings on microglia behavior in vivo.
• Analysis of studies investigating the influence of tissue acquisition and processing on microglia morphology and immune status.
• Correlation of cellular and subcellular processes in microglia during pathological conditions.

Main Results:

• Microglia are highly dynamic cells capable of responding within minutes, challenging the 'resting' state concept.
• Microglia morphology and immune status are significantly influenced by experimental procedures (tissue processing, imaging).
• Classifying microglia as 'active' or 'surveying' based on morphology alone is problematic.

Conclusions:

• A deeper understanding of microglia's dynamic behavior and the impact of experimental variables is crucial.
• The plasticity of microglia necessitates a re-evaluation of their role in CNS pathologies.
• Optimizing therapeutic interventions for brain diseases may depend on targeting specific microglia states and understanding critical time windows.