Glia 5

BIOL2052 Course Overview

• University: Southampton

• Topic: Microglia and other brain immune cells

Course Plan

1. Functional Diversity of Microglia

2. Roles of Microglia in Development and Adult Brain

3. Roles of Microglia in Chronic Neurodegeneration

Macrophage Subpopulations in the Brain

• Microglial Cells: Main immune cells in the brain

• Macrophage Types:

  • Meningeal Macrophages: Located in the meninges

  • Choroid Plexus Macrophages: Found in the choroid plexus

  • Perivascular Macrophages: Positioned in the perivascular space alongside blood vessels

Brain Development Stages

• Key Stages:

  • E9.5: Neuroepithelium colonization begins.

  • E13.5: Newborn development progresses with astrocytes, blood, and myeloid cells participation.

• Hematopoiesis: Early formation of blood cells occurs in the yolk sac, fetal liver, and bone marrow.

Microglial Types and Functions

• Surveillant Microglia: Maintain homeostasis and monitor the environment.

• Phagocytic Microglia: Involved in clearing apoptotic cells.

• Pruning Microglia: Facilitate synapse elimination during development.

• Neuromodulatory Microglia: Involved in synaptic transmission.

Microglial Diversity

• Morphological Diversity:

  • Variability in shape among microglia depending on age and regional distribution.

• Regional Density: Varies across brain regions (e.g., frontal lobe, hippocampus).

• Turnover Rates: Differ between young and aged microglia, affecting proliferation capabilities.

Microglial Function in Synaptic Pruning

• Process:

  • Microglia clear synapses during the critical period of development, particularly involving retinal ganglion cells (RGCs) in the dorsal lateral geniculate nucleus (dLGN).

• Technique: Utilizes CTB staining for tracking synaptic inputs.

Apoptotic Cell Clearance Mechanisms

• Role in Development and Adulthood:

  • Critical pathways include involvement in neuroblast development and subsequent apoptosis of excess neurons.

• Responses to Apoptosis: Microglia transition from resting to activated states performing phagocytosis.

Immune Roles of Microglia

• Inflammatory Responses: Microglia secrete pro-inflammatory cytokines (IL-1ß, TNF-α) or anti-inflammatory signals (IL-10) depending on the context.

• Chronic Neurodegeneration: Microglia exhibit altered states in response to amyloid beta pathology, contributing to neurodegenerative disease progression.

Summary of Microglial Functions

1. Phenotypically complex with regional and age-dependent diversity.

2. Essential in developing brain circuits and synaptic refinement.

3. Maintains homeostasis in healthy adult brains and modulates synaptic transmission.

4. Re-activates immune functions during environmental disruptions.

5. Central to the progression of chronic neurodegenerative diseases.