Lecture 28- Glial development I Flashcards
What are glia?
• Essentially a catch-all category for more or less everything in the nervous system excluding neurons • Glia are an extremely diverse set of cells: • Different developmental origins • Different functional roles • Diverse morphologies and profiles of gene/protein expression
What is the percentage of glia in the brain of evolutionarily different organisms?
-With increase in size and complexity of nervous system comes a huge increase in the % of the brain made up of glia -nematode: few -drosophila: 25% -mouse: 65% -human: 50-90%
What are the types of glia?
1.CNS: • Astrocytes • Oligodendrocytes • Microglia • Radial glia • Ependymal cells 2.PNS: • Schwann cells • Satellite cells • Olfactory ensheathing glia • Enteric glia
What are some characteristics of the Schwann cells?
-PNS -surround axons in PNS -are responsible for myelination of peripheral axons -participate in repair process after injury
What are some characteristics of Oligodendrocytes?
-CNS -myelinate CNS axons -provide structural framework
What are some characteristics of Astrocytes?
-CNS -maintain blood-brain barrier -provide structural support -regulate ion, nutrient and dissolved gas concentrations -absorb and recycle neurotransmitters -form scar tissue after injury -regulate blood flow -regulate synpatogenesis
What are some characteristics of Microglia?
-CNS -immune cells of the CNS -remove cell debris, wastes and pathogenes by phagocytosis -present antigens to T cells in disease -participate in synaptic pruning? (maybe) -macrophages of the brain
How do oligodendrocytes make the myelin sheaths on axons?
-the oligodendrocytes will extend processes that will wrap around an axon to insulate -all oligodendrocytes are myelinating
What are two types of Schwann cells?
-Myelinating (large diameter axons) -Non-myelinating (small diameter axons!Remak bundles)= these provide protection to the axons
What can the Schwann cell do when there is an injury?
-Can become phagocytic in presence of injury
How do Schwann cells myelinate the PNS axons?
-secrete components of the basil lamina and extracellular matrix
What are the most abundant cells of the human CNS?
-astrocytes
What are the two types of astrocytes?
-fibrous astrocytes (white matter) -protoplasmic astrocyte (grey matter)
What are the roles of of astrocytes?
- Express high levels of glutamate transporters: prevent excessive glutamate build-up around synapses
- Similarly, buffer extracellular K+ to prevent it interfering with propagation of action potentials
- Link synapses with blood vessels to couple neuronal activity with regional blood flow/glucose delivery
- one of the main roles= have glutamate transporters= clean up the neurotransmitter so it doesn’t become toxic
- also clean up K+ -link synapses to blood flow= some of the processes signal to blood vessel to increase blood in the region etc.
- fMRI really looks at the activity of the astrocytes= the blood flow at the receiving end of the astrocytes

What is the tripartite synapse?
- Astrocytes also believed to form part of the “tripartite synapse”
- Astrocytes have processes adjacent to synapses • Upon neurotransmitter release astrocytes also activated (as evidenced by increased intracellular Ca2+ levels)
- This in turn can lead to release of neuromodulatory substances such as glutamate, ATP and adenosine
- when synapses release transmitter= astrocytes can respond, can regulate the blood flow an dcan release ATP and adenosine
- modulate synaptic function

What was the experiment with injecting human astrocytes into mice?
-took out human astrocytes and injected to mice= they were better in learning, memory than the control mice that had mice astrocytes injected =suggests the astrocytes are important in learning -• Engraftment of human astrocytes into mice has recently been shown to improve their performance in some learning tasks • How much of our cognitive processing is due to glia?
What are some more roles for microglia?
• Also first systematically described by Pio del Rio Hortega • Described as “microglia” to distinguish them from “macroglia” (astrocytes) –physiological role= phacoytosis of debri, dead cells etc. -microglia swicth between two states, resting and active (ameboid) state= the one where phagocytosis happens -• Major physiological role is the phagocytosis of cellular debris and pathogens • Are thought to be the antigen presenting cells of the CNS (interact with T-cells in injury) -• Highly reactive to disruptions to normal homeostasis or injury, however:
What are the two states of the microglia?
- Ramified 2. Amoeboid
What are the stages in neural cell birth?
- Pulse-chase labelling studies using tritiated thymidine or retrovirus to birth date cells led to the model of sequential specification of neurons, then glia
- seems that there are stages in development when different cells are born
- first neurons hen glia
- neurogenesis, then astrogliogenesis and then oligodendrogenesis

How does the shift from specification of neurons to glia occur?
- This shift is due to changes in both extracellular gliogenic signals and the instrinsic properties of the neural stem cells
- the shift is due to the environement of the brain -intrinsic change in the stem cells in the brain, at later stages= only glia born

What is the overly simplistic model for the development of specification of neurons vs glia?
-early stages= neurogenic stage, later gliogenic stage

What is the current model of the specification of neurons vs glia?
- Current model more complex, however, and needs to take into account a number of different stem cell and progenitor populations
- this is the total model, do not have to remember this in detail
- even early on get glial progenitor cells
- at first neural stem cells giving rise mainly to neurons, later both neurons and intermediate prglial progenitor cells and later shoft to the glial only

What is the rest of the lecture about?
-generation of astrocytes and microglia
What do astrocytes arise from?
- Astrocytes thought to arise directly from radial glial cells during development
- radial glial cell gives rise to astrocytes







