DGN - Glia

Question 1

What are Macroglia?

Answer 1

Macroglia is a made-up term to define all components which are not microglia

Question 2

What are the main functions of glial cells? (4)

Answer 2

1. to surround neurons and provide physical support (hold them in place)
2. to supply nutrients and oxygen to neurons
3. to insulate one neuron from another and facilitate synaptic communication
4. to destroy and remove cell debris and unwanted molecules

Question 3

What are 3 other glial functions?

Answer 3

1. Glia have important developmental roles, guiding migration of neurons in early development, and producing molecules that modify the growth of axons and dendrites.
2. Glia are also active participants in synaptic transmission, regulating clearance of neurotransmitter from the synaptic cleft, releasing factors such as ATP which modulate presynaptic function, and even releasing neurotransmitters themselves.
3. Glia play a fundamental role in brain disease and degeneration, defining the pathophysiological trajectory

Question 4

Describe the history of glial cell discovery

Answer 4

• The discovery of neuroglia is usually credited to Rudolf Virchow
• The first description of glia was much earlier, when French physician Rene Dutrochet noted small globules among the large globules of the mollusk nervous system in 1824
• Otto Deiters claimed the defining feature of these new cells was their lack of axon
• Andriezen recognized two types of glia in 1893, ectodermal fibrous glia in the white matter and mesoblastic protoplasmic glia in the gray matter
• Ramon y Cajal agreed with the classification but argued that both came from the ectoderm

Question 5

What 4 classes was the glia put into by Pio del Rio Hortega?

Answer 5

• Protoplasmic in gray matter
• Neuroglia in white matter
• Mesoblastic microglia
• Interfascicular glia

Question 6

What are the stages of brain development during the post-conception weeks?

Answer 6

Age 9-20 PCW

• Neurogenesis

Age 10-38 PCW

• Neuronal migration

Age 1-9 years

• Synaptogenesis
• Gliogenesis

Age 1-15 years

• Myelination

Age 5-20 years

• Synaptic pruning

Question 7

What are radial glia and their roles in brain development? (2)

Answer 7

• They differentiate from neural progenitors early in development, with somata in the ventricular zone and extending prolongations to the pia
• They can give rise to all cell lineages, contributing to populate the brain and providing a scaffold for neuronal migration

Question 8

What gives rise to astrocytes and oligodendrocytes?

Answer 8

Key stage O2A progenitor that can give rise to astrocytes and oligodendrocytes

• Cells acquire identity as they migrate and colonise specific regions, defined by the factors the encounter

Oligodendrocyte differentiation is a stepwise programme from NG2 precursors to mature myelinating oligodendrocytes

Question 9

What gives rise to schwann cells and what do they differentiate into? (3)

Answer 9

• Neural crest cells give rise to Schwann cell precursors, also give rise to peripheral sensory and autonomic neurones and satellite cells of the dorsal root ganglia.
• Immature Schwann cells differentiate into myelinating or non-myelinating depending on early association with large or small diameter axons, respectively
• Their de-differentiation is an important process during Wallerian degeneration

Question 10

Describe the development and functional heterogeneity of astrocytes (3)

Answer 10

Unlike OLs, the stages of astrocyte lineage development are poorly defined, lacking stage-specific markers and clearly defined developmental endpoints

• Astrocyte functional heterogeneity is starting to emerge suggesting the number and role of subpopulations is yet to be defined

Neural stem cell → Astrocyte precursor → Astrocyte

• Shh used to go from neural stem cell to precursor
• Notch used to go from precursor to astrocyte
• Sox9 and NFIA used in astrocyte specificity