Glia Flashcards
What are glia?
They surround neurons and provide insulation.
What are the four types of vertebrate glial cell?
Astroglia, microglia, oligodendroglia, schwann cells.
What is the function of astroglia?
Star-shaped, symmetrical, nutritive and have a support function.
What are the features and function of microglia?
Small, mesodermally derived, have a defensive function.
What is the feature and function of oligodendroglia?
Asymmetrical, form myeline, around axons in brain and spinal cord.
What are the features and functions of Schwann cells?
Asymmetrical, wrap around the peripheral nerves to form myelin.
What are neural cells?
Neurons and glia.
What are neuronal cells?
Neurons.
What cells are included in glia?
Macroglia and microglia.
What cells are included in macroglia?
Astrocytes, radial glia, oligodendroglia and schwann cells.
What do oligodendroglia act as?
CNS myelin.
What do schwann cells act as?
PNS myelin.
What are the types of myelinating glia?
Oligodendroglia and Schwann cells.
What is myelination important for?
Increasing the rate of action potential transmission.
What are the other types of glia?
Radial glia.
What is the function of radial glia?
Embryonic scaffold throughout the CNS, guides for radial migration of neurons and produce matrix and adhesion proteins.
What happens to radial glia in adults?
Radial glia persist in the cerebellum and in the retina.
What are radial glia called in the cerebellum?
Bergmann glia.
What are radial glia called in the retina?
Muller cells.
What are ependymal cells?
They line central canal and ventricles of the brain and have beating cilia when lining the ventricles.
What types of cells are ependymal cells?
They are cuboidal cells but they have no basement membrane.
What do specialised ependymal cells participate in?
The secretion of cerebral spinal fluid.
What does cerebral spinal fluid contain?
Nutrients important for the brains wellbeing.
What cells originate from the neural tube?
The neurons, astrocytes and oligodendrocytes.
What cells originate from the neural crest?
Schwann cells.
What cells are derived from outside the developing nervous system?
Microglia - derived from macrophages and the yolk sac. It was originally thought they were only derived from macrophages, but the main source is actually the yolk sac.
What is gliogenesis?
Formation of glial cells.
What gives rise to glial precursor cells?
The neural stem cells.
What can glial precursor cells differentiate into?
Astrocyte precursor cells or O2A progenitor cells (oligodendrocytes, type 2A atrocytes formation).
What are the only astrocytes that exist in vivo?
Type 1 - type 2 only exist in culture.
What are the physical characteristics of microglia?
Small cell body, extensive projections with many branches.
What role do microglia have?
Breaking down cells and material in the brain.
How does the origin of microglia differ from other glial cells?
From the yolk sac - it contains cells that give rise to the blood and microglia. During the early stage before the formation of the blood brain barrier, primitive macrophages will migrate into the brain and become microglia. There is evidence that they originate directly from the blood from monocytes that invade the brain.
What is the evidence for the monocytic origin of microglia?
Generating chimeric embryos - bone marrow shows that the brain becomes populated by donor specific cells of the haemopoetic origin - donor cells can be labelled to visualise this migration.
What is other evidence for monocytic origin of microglia?
Microglia share many cell surface and cytoplasmic antigens exclusively restricted to macrophages.
What are the types of microglia?
Ameboid, ramified.
What are the features of ameboid microglia?
They are round cells that are clustered and found in development. They develop in cultures of glia derived from neonatal brain. The are concentratd in the corpus collosum and proliferate.
What are the features of ramified microglia?
They are the adult form of microglia that are found in the brain. They have numerous, fine processes. They are found in resting states and do not proliferate at this point.
What are the activation states of adult microglia?
Resting (ramified), activated and phagocytic.
What are the differences between the different activation states of adult microglia?
Resting have fine processes OX-42. activated have thick processes, vimetin, OX-42, they proliferate and migrate whereas phagocytic are globular, vimetin, OX-42, Ox-8 and proliferate.
How can resting microglia be removed from the resting state?
Activation - sent to a pathway that allows them to deal with threats from the nervous system.
What is vimetin involved in?
Microglia activation.
What happens if microglia are taken away from astrocytes?
They will become activated and won’t stay like microglia for long.
What is the function of resting cells?
They provide support and protect neurones. Microglia release growth factors.
How are microglia activated?
Presence of viral/other antigens - there is migration towards these substances.
What do microglia release when they are activated?
Substances the kill such as superoxide, nitric oxide and pro-inflammatory cytokines. They respond to degraded neurons to attack and remove damaged neurons.
What role do resting microglia have?
A supportive role.
What are the stages in microglial activation?
Ramified (resting), withdrawel, transitional, motile and locomotory.
What are some microglia stimulators?
Viruses, bacteria, dead cell/debris, damaged neurons, neuronal degradation, activated astrocytes - these release cytokines that can trigger microglial activation.
What is it thought that proteins do that are produced by neurons in neurodegenerative diseases?
They cause microglia to become activated and kill neurons due to the production of reactive oxygen species.
What is another idea about the role of microglia in cell death?
Whether microglia do not play an active role in killing healthy cells in the brain and that they respond to damaged neurons by killing them.
What happens if ALS?
Microglia are activated and produced substances that bring about microglial death. It is unclear whether the microglia cause this death or if they are playing an additional role with breakdown of neurons.
What is ALS?
Motor neuron disease.
How many astrocytes are there per neuron in the brain?
50 per neuron.
What are the two types of astrocytes?
Protoplasmic astrocytes and fibrous astrocytes.
How do the two different types of astrocytes vary?
Protoplasmic astrocytes are associated with grey matter/cell somas of neurons. Fibrous astrocytes are associated with cell axons/white matter.
What is the function of protoplasmic astrocytes?
They maintain the blood brain barrier, the interstitial environment and they transport processes for K+ and glucose.
What is the function of fibrous astrocytes?
The provide support and structure and form scar tissue.
What can glial fibrillary acidic protein (GFAP) be used for?
It stains astrocytes and makes them very visible.
What is GFAP?
Glial fibrillary acific protein - it is an intermediate filament.
What are perivascular feet?
Projections from astrocytes that make contacts wiht blood vessels. They are foot processes.
What are the functions of astrocytes in development?
They provide the pathways used by neurons to migrate to their appropriate sites.
What are the key functions of astrocytes in providing pathways for neurons?
They have a role in axonal guidance (ability of axon of neuront o connect to its correct target), they create boundaries/decision points for axonal movement.
What are the proteins involved in pathfinding in astrocytes?
CAMs, cadherins, integrins and selectins.
What is the function of CAM molecules on neurons?
They can interact with molecules expressed on the cell surface of astrocytes.
What are the functions of astrocytes?
Pathfinding, support, growth and death, calcium signalling, clearing glutamate release, formation of the blood brain barrier, K+ and glucose transport, expression of channels and neurotransmitter receptors, ability to shrink and expand - extracellular volume.
What position do astrocytes have around synapses?
They wrap around the pre and post synaptic neuron to provide physical support.
What factors do astrocytes release?
Growth factors, cytokines which are important for the survival and development of neurons.
What happens, involving astrocytes, during axonal damage?
Astrocytes proliferate around the site of damage to aid repair or to form a glial scar that can inhibit axonal regeneration.
What is the function of glial scars?
They prevent axonal regeneration.
What are the connections between astrocytes called?
Gap junctions.
What is the function of gap junctions?
They allow the transport of ions through into other cells. Astrocytes can communicate with each other using calcium.
What is the movement of calcium between astrocytes called?
A calcium wave - this can signal from interconnected astrocytes around a neuron to regulate the function of the nervous system to change - synchronising the way neurons behave.
How do astrocyte waves effect calcium levels?
There is reduced calcium in the cleft, meaning there is inhibited neurotransmitter release despite the arrival of action potentials. Only with termination of the astrocytic calcium wave will levels return to the original levels in the cleft, allowing neurotransmitter release at high levels.
Why are astrocytes important in glutamate levels?
Excess glutamate is released at synapses, but too much glutamate can cause excitotoxicity so these levels need to be regulated.
What do astrocytes express to prevent excitotoxicity?
GLAST, GLT-1 that are glutamate transporters that take up glutamate and clear it from the synapse.
What happens when glutamate has been taken up by glutamate transporters?
It is converted to glutamine and returned to neurons where glutamate can be formed again for release.
What is the blood brain barrier?
A barrier in the brain that stops molecules entering - immune privilege, prevents being attacked by immune cells of the blood.
What cells cannot cross the blood brain barrier?
Immune effector molecules eg. immunoglobulin and complement, naive T cells.
What happens, in terms of neutrophil recruitment, following excitotoxin-mediated neuronal degeneration?
Minimal neutrophil recruitment.
What are allografts?
Transplanted tissues from donors.
Why are allografts rejected in most parts of the body?
Lack of immunological compatability.
Where are allografts not rejected from?
In the CNS.
What is the immunological privilege provided by the blood brain barrier important for?
It is important for allografts, as much transplants are rejected due to lack of immunological compatability, but this is not an issue in the CNS.
What are potassium levels important for?
Neuronal function - potassium clearance is controlled by astrocytes.
What is the expression of serotonin receptor important for on astrocytes?
Helps coordinate the activity of astrocytes with the neurons and helps of clearance of ions that help maintain normal levels of these ions extracellularly.
What is important about the ability of astrocytes to change size?
Extracellular volume - they can modulate the amount of free space around synapses, which can e.g. decrease the area that neurotransmitters/otehr molecules can move and may facilitate the function of the neurotransmitters.
What does astrocytic swelling occur due to?
Glutamate and adenosine receptor stimulation.
What can be induced in astrocytes by focal application of glutamate?
Filopodial extension/outgrowth of membrane.
What happens if the extracellular volume fraction decreases?
There is an increased concentration of extracellular molecules and increased effective concentrations of neurotransmitters - reduced space at the synapse means neurotransmitters are more likely to bind.
What is the overall effect of astrocytes changing shape on neurons?
It can influence the excitability of neurons.
What are cytokines produced by?
Astrocytes, microglia and neurons.
What effect do cytokines have in the nervous system?
They can alter cell survival and proliferation.
What determines the action of cytokines?
Their point of release, the cells they act upon and their concentration.
What are some common cytokines?
Interferons, interleukins, tumor necrosis factor (TNF) family, transforming growth factor family (TGF), chemokines, colony stimulating factors (CSF), and a variety of related protein that can also act as growth factors such as cilliary neuotrophic factor.
What are the differences between pro and anti inflammatory cytokines?
Proinflammatory - negative response, antiinflammatory - positive response.
What must target cells for cytokines express?
Receptors - there are a lot of different receptors on microglia/astrocytes/oligdendrocytes.
What happens once a cytokine has bound to a receptor?
There is an effect on protein expression - main pathway associated with activity is the JAK pathway.
What is the JAK pathway?
Associated with a variety of different cytokine systems. Proteins dimerize as a result of phosphorylation and allows them to interact with other proteins or enter the nucleus to modulate DNA expression/proteins,
