Glial cells 2

BIOL2052 Overview

  • Course: BIOL2052 at University of Southampton

  • Topic: Lineage and development of glial cells II: Microglia

Presentation Plan

  1. Introduction and quick history

  2. Microglial development and functions

  3. New insights and open questions

Key points on Microglia

  • Microglia are Macrophages:

    • Microglia function as macrophages and are part of the brain's immune cell population.

Immune Census of the Brain

  • Study using naVive C57BL/6 mice to analyze brain immune composition.

  • Key brain immune cell types:

    • Parenchyma, meninges, and choroid plexus.

    • Use of single-cell dissociation and mass cytometry (CyTOF) for assessment.

    • Diverse immune cell types contributing to brain immunity, including T cells, B cells, and various myeloid cells.

Macrophage Subpopulations in the Brain

  • Different Subpopulations:

    • Microglial cells, meningeal macrophages, and choroid plexus macrophages.

    • Identifies locations such as perivascular spaces and different brain regions.

Structure of Microglia

  • Microglia are characterized by ramified morphology.

  • Population Features:

    • Variability in morphology, covering different brain regions.

    • Equipped with immune sensors for rapid response to disturbances.

Functionality of Microglia

  • Involved in immunosurveillance, synaptic pruning, and maintaining brain homeostasis.

  • Play a role in antigen presentation to T cells.

Historical Perspective of Microglia

  • Milestones:

    • Nissl staining in the 1880s allowed for visualizing microglia.

    • Discovery of their relationship to macrophages in the early 20th century.

    • Significant findings about their behavior during inflammatory responses.

  • Key Figures:

    • Pío del Río Hortega named the cells 'microglia' and characterized their functions.

Development of Microglia

  • Microglial cells originate primarily from erythromyeloid progenitors derived from the yolk sac.

  • Development Process:

    • The shift from amoeboid to ramified forms occurs within the first two postnatal weeks.

    • Influenced by various environmental factors such as CSF1, IL34, and TGFβ.

Diversity of Microglial Populations

  • Microglia experience diversity throughout the lifespan of mice from prenatal stages to adulthood and pathology.

  • Variations in Gene Expression:

    • Stage-specific microglial subpopulations emerge during development, with unique functional characteristics.

Microglial Dynamics in Adulthood

  • Population Maintenance:

    • Balanced turnover through proliferation (up to ~2% daily) and apoptosis.

    • The adult microglial population remains stable and does not significantly replace during healthy aging.

    • Significant findings on the factors that regulate proliferation and cell death in microglial populations, especially in response to damage or disease.

Summary

  1. The brain's immune system is complex and diverse.

  2. Microglia play critical roles in development and maintenance of brain functionality.

  3. Development of microglia follows a structured program from progenitors.

  4. Stability of most macrophages in adulthood.