DGN - Microglia

Question 1

What are the macrophage subpopulations in the brain? (5)

Answer 1

• Microglial cells
• Meningeal macrophages
• Perivascular macrophages
• Dendritic cells
• Chloroid plexus macrophage

Question 2

Basic characteristics of the microglial population (4)

Answer 2

• Ramified morphology, tiling the brain parenchyma in a mosaic-like distribution
• Biggest differences in morphology between grey (ramified) and white (bipolar) matter
• Variable densities in different regions, with each cell covering an average volume of 50000microm3
• Equipped with a repertoire of immune “sensors” and “reactants”, allowing rapid and plastic reactions to disruptions of the brain’s homeostasis

Question 3

What is the history of microglia research? (3)

Answer 3

• Microglia were first described in 1880 by Nissl and Robertson, who showed their relation to macrophages
• Victor Babeş noted the activation of microglia and the formation of ramified clusters in 1897
• Pío del Río Hortega coined the term “microglia” around 1920 and is considered the “Father of Microglia.”

Question 4

What is the contribution of Hickey and Kimura to microglial research?

Answer 4

In 1988, Hickey and Kimura demonstrated that perivascular microglial cells are bone-marrow derived and express high levels of MHC class II proteins

Question 5

How are macrophage populations in the brain colonized during development?

Answer 5

Macrophage populations in the brain are colonized by erythromyeloid progenitors (EMPs) derived from the yolk sac.

• These EMPs develop into primitive macrophages (pMac) and then differentiate into microglia

Question 6

Why are fetal liver monocytes unable to contribute to brain development in adults?

Answer 6

They cannot cross the BBB

Question 7

What do EMPs develop into?

Answer 7

The macrophage ancestor population A1 (CD45+, CX3CR1low, F4/80low) into the A2 (CD45+, CX3CR1hi, F4/80hi) progenitor population that commit to microglial cells

Question 8

What are Amoeboid cells?

Answer 8

Persist during the first 2 weeks of the postnatal brain where they gradually acquire the ramified shape characteristic of microglia in the steady state

Question 9

What factors drive the specification of microglia during development?

Answer 9

Environmental factors such as CSF1, IL34, and TGFβ play fundamental roles in shaping, maintaining, and reinforcing microglial identity during development

Question 10

Which transcription factors are involved in microglia specification?

Answer 10

Several transcription factors, including PU.1, C/EBPs, RUNX1, IRF8, SALL1, SALL3, MEIS3, and MAFB, are involved in microglia specification and fate acquisition

Question 11

How were different populations of microglia discovered?

Answer 11

RNA sequencing

Question 12

How is the adult microglial population maintained?

Answer 12

The adult microglial population is maintained by a fine balance of proliferation and apoptosis, with microglia proliferating at a rate of 0.69%