Glia Flashcards
Ratio of glia:neuron
10:1
Resident macrophages of the brain
Microglia
Glia cell that makes myelin in PNS
Schwann cells
Glia cell that make myelin in CNS
Oligodendrocytes
Neural tube origin (3)
Oligodendrocytes, Astrocytes, and neurons
Neural crest origin (1)
Schwann cell
(Oligo/Schwan cells) can differentiate without neuronal signals, while (oligo/schwann cell) needs neuronal signals to differentiate
Oligos don’t need signal, schwann need signal
Myelin is an extension of?
Plasma membrane of schwann cells/ oligodendrocytes
Which cell (and where) can insulate up to 40 different axon segments?
Oligos, in CNS
Which cell (and where) can insulate ONLY ONE axon segment?
Schwann cell, in PNS
These cells form Remak bundles around neurons
Non-myelinating Schwann cells (Sensory C-fibers)
Molecular architecture of compact myelin consist of these two lines
Intraperiod lines (between membranes, external layer) Major dense lines (membrane, cytoplasmic part)
This protein holds internal surfaces together and seal up the major dense lines
Myelin basic protein (MBP)
This protein involved in keeping myelin sheath compact is only found in CNS
PLP
This protein involved in keeping myelin sheath compact is only found in PNS
PMP22
This lipid has a major role in keeping myelin compact
Glycosphingolipids (GSL)
Mutations in these components of compact myelin result in many different disorders
PLP - Pelizaeus Merzbacher Disease
PMP22, P0, Cx32 - Charcot marie Tooth Disease
GSL- Leukodystrophies (lipid storage diseases)
What is the percent composition of lipid and protein in CNS myelin? How does this compare to entire brain?
CNS myelin- 70% lipid, 30% protein
Whole brain- lipid
Channels that transverse through myelin
Schmidt-Lanterman cleft
Site of myelin attachment to the axon, found next to Nodes of Ranvier, where myelin loops get attached
Paranodal region
In addition to Schwann cells, what else covers some of myelin in PNS?
Microvilli
There are no microvilli present in CNS; what instead covers the nodal region?
Astrocytes, function still unclear
Three important molecules that are important in myelin-axon interaction. What happens if these are removed?
Caspr, Lipids, NF155.
If ands not formed, paranodes to not form resulting in bad connection with neurons. Shaking
In addition to increasing nerve conduction velocity and saltatory conduction (propagation of action potential), what are two other functions of myelin?
- Bi-directional signaling
2. Inhibits axon regeneration (CNS myelin) - not good!
Glia to neuron interaction
Bi-directional signaling
Two things that inhibit regernation of axons in CNS
- degenerating myelin- produce inhibitory signals
2. Astrocytes- come in and make scars
Lack of axon regeneration is a major problem in these type of injuries
Spinal cord injury,
Why can a cut axon in the PNS regenerate axons?
Myelin gets cleared up efficiently, Schwann cells produce growth promoting signals
Why can Schwann cells help regenerate axons while oligos cannot?
Schwann cells have the capacity to re-differnetiate into progenitor cells if get damaging signals, can produce growth factors and make myelin and help regenerate axons. Oligos don’t have this ability and just die.
Why is multiple sclerosis not just a disease of myelin?
Huge axonal component, in later stages, it’s irreversible situation, because cannot regenerate axons even if can figure out how to make myelin.
Briefly describe course of MS progession
Cycles between relapse and remission, increasing disability with each cycle
In MS, conduction is temporarily restored. What is the explanation for this?
Conduction restored by increase in density of sodium channels. But eventually, axons die, and there is a prominent conduction loss
During demyelination, oligos die. What cells migrate from other regions and proliferate and differentiate into oligos to help remyelinate?
Oligodendrocyte progenitor cells (OPCs)
Two possible explanations for remyelination failure
- Failure of OPC recruitment
2. Failure of OPC differentiation
4 types of Glia
- Astrocytes
- Oligodendrocytes
- Polydendrocytes
- *microglia
*immune cell, not derived from neural progenitor
Oligos and astrocytes come from what cell
Neuroepithelial stem cells (which can also go to form neurons)
This cell makes up what percent of cellular volume of CNS, and what percent of total cell number
90% of CNS cell volume, 50% of total cell number
Astrocytes are identified by what 3 cell-specific proteins?
GFAP (glial fibrillary acidic protein), vimentin, S100Beta
Process where never cells are damaged and killed by excessive neurotransmitter stimulation
excitoxicity
These astrocyte-secrete proteins help regulate synaptogenesis
hevin, SPARC
Gliotransmitter
chemicals released from glial cells that help neuronal communication between neurons and other glial cells (indistinguishable from neurotransmitters)
Astrocytes are the intermediate in this relationship between the neuronal activity and local blood flow changes
Neurovascular coupling
True/False: Astrocytes regulate sleep
True
Tripartite synapse
Astrocytes are key player in chemical communication between 2 neurons
- pre synaptic
- post synaptic
- astrocyte- can absorb and emit neurotransmiters
How do astrocytes play role in blood pressure?
Have feet on blood vessel in addition to feet on pre and post synaptic terminals
Astrocytes can secrete these two substances that will lead to different activities of neuronal cell due to change in what intracellular levels?
Adenosine/ADP or glutamate, change in intracellular calcium levels
Astrocytes assist brain and protects harm caused by
inflammation
When glial cells function improperly, present as neurodegenerative disease
Gliodystrophy
Lou Gehrig’s disease
ALS (amyotrophic lateral sclerosis)
ALS
Upper and lower motor neuron degeneration, symptoms include muscle twitching, weakness, stiffness, cramping, clumsiness, muscle atrophy
3 ways astrocytes can mediate neurotoxicity (role of astrocytes in ALS)
- failure to provide trophic support
- react to and amplify neural dysfunction
- produce neurotoxins (start pumping out toxins that will kill motorneurons
In experiment when extracted astrocytes from mouse with ALS, astrocytes were toxic to what?
All motorneurons
ALS is a neurodegenerative disease, but it is CAUSED by
astrocytes (secrete factors toxic to motorneurons-kill them)
Microglia can be identified by these three cell-specific proteins
Iba-1, CD11b, CD45
Microglia originate from this region
Bone marrow
Fate mapping analysis reveals that adult microglia derive from
primitive macrophages
True or false: Microglia function like macrophages, and have the same role as macrophages.
FALSE. They function like macrophages, but have unique roles from macrophages. They are a specialized cell type to the BRAIN.
What happens to microglia when activated?
Change shape, proliferate, and migrate. Very motile to monitor environemnt
Globoid cell Leukodystrophy
Malignant microglia, genetic disease in mutation to form myelin, microglia are hyperactive, excessively chew up oligos
Activated microglia have (same/different) proteins than cells that are “quiet”
Different proteins. Can use MRI and PET to see areas of brain that have heightened levels of microglial activity
This brain structure has an important link to Parkinson’s disease
Substantia nigra- see very active microglia in someone with parkinsons
Area of brain that plays important role in reward, addiction, and movement
Substantia nigra
Parkinson’s disease is characterized by death of this
dopaminergic neurons
What would a MAO deficiency cause high levels of?
Catecholamines (monoamine oxidase is responsible for degradation)
Flight or fight response
Catecholamines
Microglial activity corresponds with the location of what?
Brain atrophy
What are three ways microglia help with homeostasis and regenerative roles?
- Promote neurogenesis
- Maintain synapse integrity
- Clear cellular debris to promote repair
3a. synaptic pruning
Regulatory process, reduces number of neurons and synapse, leaving more efficient synaptic configuration
synaptic/neuronal/axon pruning
