Microglia

Question 1

3 Examples of contacts for microglial communication with neuron?

Answer 1

CD200- Neurons are OK
Soluble mediators- CX3CL1
Adrenoceptors (incoming information)

Question 2

What marker is specific of macrophages?

Answer 2

CD68

Question 3

How was a microglial causal role in AD suggested?

Answer 3

TREM2 only found in microglia, and this was found in AD.

Dysregulation of beneficial function:
Amyloid deposition causes tagging of synapses with C1q. Microglia prune these.
CD33 on microglia interacts with sialic acid (neuron) and inhibits microglial phagocytosis. In AD mice, overexpression of CD33 prevents amyloid phagocytosis.

Gain of detrimental function:
Amyloid mimics DAMPs and activates microglia, which causes ROS and interleukin release.

Question 4

4 Types of CNS macrophage?

Answer 4

Microglia (Brain parenchyma)
Perivascular Macrophages (BBB)
Choroid plexus macrophages
Meningeal macrophages (circulate in CSF all around brain)

Question 5

What is the difference between origin of microglia and other CNS cells?

Answer 5

Microglia come from blood cells- common myeloid progenitors. They are MESODERMAL. Derived from yolk sac myeloid cells (not bone marrow).
Other CNS cells come from neuroectodermal or neuroepithelial progenitors.

Question 6

How do we know this?

Answer 6

Deleting PU1 stops microglial production. P1 is found on common myeloid progenitor.
Microglia are SELF RENEWING.

Question 7

3 general functions of Microglia?

Answer 7

Surveillance. (Own distinct spatial territories)
Synaptic pruning- reduce synapses post natally
Cell turnover- Cerebellum high turnover. Lots of phagocytic markers. Striatum- Low neuronal turnover .

Question 8

What happens when you turn striatal microglia to cerebellar microglia?

Answer 8

They begin to eat neurons. They are constantly regulating neurons and health!

Question 9

How do Microglia survey the environment?

SSPTIT

Answer 9

1. Own spatial territory
2. Sample extracellular environment randomly.
3. Processes directly contact axons to receive signals. Interact with neurons, vessels and astros.

4.Rapid transformation- Resting=ramified. Activation causes growth of cell bodies with retracted processes.
Cells can become hyper ramified.

5. Initiate Immune response. Endfeet on endothelial cells communicate with inflammatory cells.
6. Support endangered neurons or interfere with threats.

Question 10

What was seen during axotomy of facial nerve nucleus?

Answer 10

Microglia covered neuronal cell body.
Released TFG-B to protect neurons and promote regeneration.
Block terminals to prevent excitation- stopping metabolic burden.

Question 11

2 (3?) phenotypes of microglia?

Answer 11

Homeostatic (P2Y12)

M1/M2

Question 12

How do you activate macrophages in vitro, what phenotypes are produced?

Answer 12

Bacterial wall component (LPS): Highly proinflammatory.
(Cytokines, ROS, cytotoxicity -M1)

IL4/IL13: Reparative. (anti inflammatory cytokines, wound repair, debris clearance)

Do the above exist though? They are in vitro models.

Question 13

What are the implications of microglia in ALS and PD?

Answer 13

ALS: Early induction delays the disease. Late induction worsens disease.

PD: Density increased in PD brain. Microglial neurotoxic factors increased in post mortem brain.