08_Glial Cells_Q and A_Jonathan

Question 1

Glial cells in the CNS represent a heterogeneous population of cells with a diverse and largely unknown set of functions. These are the most numerous cells of the CNS, and it has been estimated that they encompass 90% of cells in the human CNS (perhaps even greater percent in other species and probably slightly less in rodents – 65%).

Answer 1

Glial cells in the CNS represent a heterogeneous population of cells with a diverse and largely unknown set of functions. These are the most numerous cells of the CNS, and it has been estimated that they encompass 90% of cells in the human CNS (perhaps even greater percent in other species and probably slightly less in rodents – 65%).

Question 2

Glia are classically broken down into two categories:

Answer 2

macroglia and microglia.

Question 3

Where are Macroglia derived?

Answer 3

• from the neuroectoderm.

Question 4

What are the macroglia?

Answer 4

•	oligodendrocytes
o	perineuronal
o	intrafascicular
•	astrocytes
o	fibrous
o	protoplasmic
•	ependymal cells
•	choroid plexus
•	radial glia

Question 5

Where are microglia derived from?

Answer 5

• mesoderm

Question 6

What are microglia?

Answer 6

• monocyte/macrophage

Question 7

What are Oligodendrocytes?

Answer 7

axonal ensheathing cells primarily found in the white matter

Question 8

What are Perineuronal oligodendrocytes?

Answer 8

found close to neurons in the gray matter and probably don’t myelinate, share some ultrastuctural features with other oligos; controversial and some feel they may be a completely new type of cell.

Question 9

What are Interfascicular oligodendrocytes?

Answer 9

myelinate axons to enhance electrical conduction.

Question 10

What are Fibrous astrocytes?

Answer 10

primarily in WM, long fibrillar processes that envelope Nodes of Ranvier.

Question 11

What are Protoplasmic astrocytes?

Answer 11

primarily in GM, sheet-like processes that surround synapses.

Question 12

What are Ependymal cells?

Answer 12

– specialized glial cells with cilia that form a tight columnar type alignment along ventricular and central canal linings. Choroid plexus, also specialized glial cells produce CSF, while the ependymal cells help circulate the CSF.

Question 13

What are Radial glia?

Answer 13

– specialized glia that act as “active” scaffolding in the developing CNS.

Question 14

What are Microglia?

Answer 14

• are very different types of cells that are specialized monocyte/macrophage type cells derived from the mesoderm.
• migrate into CNS from bone marrow stem cells.
• They are believed to assist in the extensive remodeling of the fetal CNS by phagocytizing cells that die normally by apoptotic cell death.

Question 15

What do microglia look like post natally?

Answer 15

• In post natal life they are small, dense, elongated nuclei without identifiable cytoplasm.
• Special stains to reveal their cytoplasm show it to be arranged as thin branches radiating from the nuclear zone.
• Microglia establish individual, non-overlapping territories.

Question 16

What percent of the nervous system is microglia?

Answer 16

o They comprise about 8-10 percent of all CNS cells.

Question 17

What do microglia do after development?

Answer 17

• Not well understood
• They may lie fairly quiescent in surveillance for some brain insult when they then become activated take on important neuroimmunologic phagoctyic functions.
• These cells will be discussed in greater detail in neuropathology next year.

Question 18

What are Schwann cells and where are they derived?

Answer 18

• from neural crest and are the glial cells of the peripheral nervous system.
• They carry out similar functions to astrocytes, oligodendrocytes, and microglia in the peripheral nervous system.
• They ensheathe motor and sensory axons to improve conduction velocities.

Question 19

What is the function of Schwann cells in the neuromuscular junction?

Answer 19

• They are also important components of the synapse at the NMJ and have the capacity to ingest tissue debris and promote regeneration after injury.

Question 20

Where do glial cells develop?

Answer 20

• Glial cells develop after the neurons within the subventricular zone (SVZ).

Question 21

What are the first two cell types in the SVZ to develop?

Answer 21

• radial glia and neurons.

Question 22

Explain glial cell development?

Answer 22

• During early brain development a dense collection of progenitor cells accumulate in the (SVZ).
• Two cell types are among the first to mature and leave this area: the radial glia and neurons.
• The radial glia have long processes that span the length of the developing cortex from pia to ventricle.
• It’s along these processes that the migrating young neurons move to populate the cortical plate.
• Once most of the neurons have left the SVZ the remaining progenitor cells within this germinal matrix then develop into protoplasmic astrocytes or oligodendrocytes.

Question 23

How do astrocytes (and other glia?) migrate into the developing brain? Are the migrating cells preformed cell lines or pleuripotent?

Answer 23

• Recent data suggests that the astrocytes migrate up the radial glia similar to the neurons.
• Additional studies also suggest that some the migrating cells are pluripotent meaning that they can develop into neurons or astrocytes.

Question 24

During what month in development are neurons born?
Astrocytes?
Oligodendrocytes?

Answer 24

• neurons are born in the second month
• astrocytes in the third month
• oligodendrocytes in the fourth and fifth months.

Question 25

When does myelination begin?

Answer 25

• Myelination begins during late gestation and continues several years into infancy in a very tract selective manner.

Question 26

What is the turnover rates of neurons, oligodendrocytes, and astrocytes?

Answer 26

• Neurons and oligodendrocytes are post-mitotic cells that persist for the life of the organism with little or no turnover (myelin does turn over but slowly and some minimal neuro- and gliogenesis may occur in select areas of the brain throughout life).
• Astrocytes have a greater capacity for turnover, but the degree of turnover throughout life is not known.

Question 27

How are the number of oligodendrocytes is perfectly matched with the number of axons needing to be myelinated?

Answer 27

• Oligodendrocyte precursors enter the developing white matter and are signaled to divide by peptide mitogens secreted by astrocytes apparently in areas of active electrical activity.
• In this way maturing, electrically functioning axons elicit the oligos to populate the area and mature themselves to begin myelination.
• Amazingly, oligos have evolved a molecular counter that tells them to stop dividing after a set number of divisions.

Question 28

What happens to the extra oligodendrocytes during development?

Answer 28

• oligos require signaling from neighboring cells in the form of trophic factors to survive.
• As with neurons, probably twice as many oligos are produced than are needed during development, and the one’s not needed undergo apoptosis.

Question 29

What are Functions of Astrocytes? (long list)

Answer 29

• partnership with neurons in maintaining normal physiology and homeostatic harmony.

A. Structural support and scaffolding especially during development

B. “Tripartite” (the pre and postsynaptic elements and glial cells) or even “tetrapartite” (the pre and postsynaptic elements, glial cells and extracellular matrix created by these cells) synapses comprise an insulated microenvironment for discrete signaling, fast uptake of neurotransmitter in the synaptic cleft, metabolic recycling of neurotransmitter, and tight coupling and trophic factor expression that contributes to maintenance and plasticity (see below).

C. Regulate and maintain extracellular potassium ion concentrations.

D. Participate in the structure and induction/maintenance of the blood brain barrier and regulation of vascular functions.

E. Produce and secrete trophic factors, neuropeptides, neurotransmitters and other small molecules like glucose necessary for other CNS cell survival and function.

F. Produce extracellular matrix proteins important possibly for axonal guidance, migration, and nuclei clustering.

G. Detoxification by sequestering metals and other neuroactive substances.

H. Calcium wave communication: in response to stimuli astrocytes can communicate as a syncytium because of interconnectedness of neighboring cells via gap junctions.

I. Astrocytes may actively control the making and breaking of synapses.

J. Multiple functions after neuropathological insult, ie. “reactive astrocytes” and “glial scars” or as the cause of the pathological insult, ie. glial tumors.