L2: Cell Biology of Glia Flashcards
___ are the non-neuronal supporting cells of the nervous system
Glia
Which nervous system do astrocytes, oligodendrocytes, and microglia belong to?
CNS
Oligodendrocytes are the glial cells that form __ ___ around axons in the CNS
Schwann cells are the glial cells that form ___ ___ around axons in the PNS
myelin sheaths
Macroglia includes: ___ and ____ lineage cells
astrocytes, oligodendrocyte lineage cells
Macroglia (as well as astrocytes and oligodendrocytes) are all derived from _____ in the embryonic neural tube and forebrain
NPC’s (neuroepithelial progenitor cells)
What do neuroepithelial progenitor cells (NPC’s) transform into?
Radial Glia
What cell type is the primary progenitor cells for both neurons and macroglia during embryogenesis?
Radial Glia
After radial glial cells generate neurons, ____ occurs and they begin differentiating into ____ or ____
Gliogenic Switch
1) Astrocytes
2) Oligodendrocyte Progenitor Cells (OPC’s)
Where are the Schwann cells in the PNS derived from?
Neural Crest
True or False: Microglia are endodermal in origin
False - microglia are MESOdermal in origin
- They are generated in the yolk sac during embryogenesis from HSC (become primitive macrophages and then cells migrate to CNS to become microglia)
Schwann cell precursors originate from ____
NCC’s (neural crest cells)
Schwann cell precursors migrate out of the ganglia and into the ____, where they continue to proliferate and differentiate into ______
peripheral nerves; immature Schwann cells
Immature Schwann cells envelop groups of axons before terminally differentiating into either: ____ or _____ cells
Myelinating or Non-myelinating (Remak) Schwann Cells
When does radial sorting occur in Schwann cell development?
During differentiation into myelinating or non-myelinating schwann cells
- Involves segregation to become individually ensheather and myelinated by myelinating Schwann cells
The non-myelinating Schwann cells bundle multiple smaller diameter unmyelinated axons into ___ ___
Remak Fibers
Schwann cells are surrounded by a ____ ___, a structure that supports nerve and guides axonal regeneration after peripheral nerve injury
basal lamina
What determines the phenotypic differentiation of Schwann cells to become either myelinating or non-myelinating cells?
The axon
True or False: Schwann cells contribute to the survival, guidance, and differentiation of axons, as well as their architecture and distribution of ion channels
True
Describe the stage of Schwann cell differentiation
True or False: Myelinated astrocytes are highly polarized cells, longitudinally and radially
False - myelinating schwann cells are highly polarized longitudinally and radially
What are the four ways in which myelinating Schwann cells are longitudinally organized?
1) Nodally
2) Paranodally
3) Juxtaparanodally
4) Internodally
True or False: The paranodal domain is the largest longitudinal domain of the myelinating schwann cell
False - the internodal domain is the largest, makes up the length of the Schwann cel
What is another name for the nodal region of the myelinated Schwann cell?
Node of Ranvier
The Node of Ranvier contains sodium channels and an assembly of proteins. What do these structures facilitate?
Saltatory propagation of action potential
Radially, Schwann cells are organized into an inner and outer compartment, which are known as?
Inner = Adaxonal
Outer = Abaxonal
Which radial compartment (the adaxonal or the abaxonal) of the schwann cell mediates interactions w basal lamina and contains the nucleus?
Abadxonal domain
What is located between the adaxonal and abaxonal domains?
Compact myelin sheath, composed by lamellae (many layers of the schwann cell membrane)
How many myelin internodes are formed by a single schwann cell?
How many myelin sheaths are formed by a single oligodendrocyte?
One
Dozens of myelin sheaths in the CNS
True or False: The myelin of an oligodendrocyte is often thicker than CNS myelin
True
True or False: Myelin is a low resistance and high capacitance membrane that is essential for saltatory propagation of the AP
False - while myelin is essential for saltatory propagation of the AP, it is high resistance and low capacitance
Compact myelin is interrupted by ____ incisures
Schmidt-Lanterman Incisures (located along internode and retain cytoplasm)
_______: clefts considered as channels for communication between inner and outer collars of cytoplasm via: gap junctions (formed b/w adjacent membranes)
Schmidt-Lanterman Incisures
In adult nerves, the fiber is covered by a collagen-rich and vascularized extracellular matrix known as the ____
Endoneurium
True or False: The endoneurium covers the basal lamina that surrounds the axon-Schwann cell unit
True
Groups of axons-Schwann cell units are bundled together as ____ via a muli-layered tube known as the ____
nerve fascicles; perineurium
___: the fibrous and dense coat the covers the external portion of nerves and fills the spaces between nerve fascicles
Epineurium
What are the two main types of peripheral nerve injuries?
1) Axonotmesis: axon is disrupted, but connective tissue sheath and schwann cell basal lamina tube are intact
2) Neurotmesis: axon, connective tissue sheath, and schwann cell basal lamina are ALL interrupted
True or False: Neurotmesis usually has very efficient recovery and is modeled by nerve crush in rodents
False - neurotmesis usually has a very POOR recovery and is modeled by nerve CUT in rodents
Axonotmesis has very ___ recovery and is modeled by nerve ___ in rodents
efficient; crush
In a nerve cut, when the proximal and distal end stumps are reattached, a small gap is generated that is bridged by ___ units formed by Schwann cells from each stump and they carry the regrowing axons from the proximal stump along them
regeneration units
Describe Neutromesis:
In the nerve cut (as occurs in neutromesis) - why is functional nerve recovery usually poor?
Targeting errors or regenerating axons that occurs at interphase (between proximal and distal nerve stumps)
In the distal end, the axons degenerate and there is a complex process known as ____ ___ that involves Schwann cells, fibroblasts, macrophages, and blood borne cells, which build an environment that supports survival of injured axons
Wallerian Degeneration
How do schwann cells behave differently than oligodendrocytes s/p peripheral nerve injury?
Schwann cells TRANSDIFFERENTIATE to clear cellular debris + coordinate repair
True or False: Oligodendrocytes respond fast to peripheral nerve injury by proliferating and transdifferentiating from myelinating to nonmyelinated or immature oligodendrocyte cells
False - SCHWANN cells respond fast to peripheral nerve injury by proliferating and transdifferentiating from myelinating to non-myelinated or immature SCHWANN cells
The transformation process by which schwann cell proliferate and differentiate (myelinating or no vs. immature) s/p peripheral n. injury is controlled by _____, a transcriptional factor
c-Jun
True or False: c-Jun is rapidly upregulated in Schwann cells present anterior to the nerve injury
FALSE - c-Jun is rapidly upregulated in Schwann cells present DISTAL to the nerve injury
____ are the predominant repair Schwann cells in the distal nerve stump and support nerve repair process
Bungner Schwann Cells
Repair (Bungner) Schwann cells form the regeneration tracks, also known as the: ____
Bands of Bungner
What are four ways in which Repair (Bungner) Schwann cells in the distal nerve stump support nerve repair process?
1) Express neutro-trophic factors
- support survival of injured neurons and axonal elongation
2) Express cytokines (recruits macrophages that clear cell debris)
3) Activate cell-intrinsic myelin breakdown process (autophagy)
4) Generate regeneration tracks
- from injury site to nerve target area
- help guide regenerating axons
True or False: Bands of Bungner are composed of elongating bipolar Schwann cells
True
What disease can arise if there is mutation in several myelin or gap junction proteins expressed in myelinating schwann cells?
Charcot-Marie-Tooth Disease
True or False: Charcot-Marie-Tooth Disease is the most common hereditary neuropathy and is characterized by demyelination, conduction block, secondary axonal degeneration, and neuronal loss
True
True or False: Disruption of Schwann cell-neuronal interaction may cause the neuronal loss, as seen in Charcot-Marie-Tooth Disease
True
True or False: Demyelination in CMT leads to axon degeneration, neuron loss, and conduction block
True
True or False: Oligodendrocytes lineage cells arise from the neuroepithelial progenitor cells (NPC’s) of the embryonic neural tube and forebran
True
Neuroepithelial progenitor cells (NPC’s) transform into radial glial, which are progenitor cells for both ___ and ___ (e.g astrocytes and oligodendrocytes)
neurons; macroglia
Oligodendrocyte progenitor cells (OPC’s) are also known as ___ cells
NG2 cells (since they express this proteoglycan on their surface)
True or False: OPC’s emerge from radial glial and arise from ventricular zones of the embryonic neural tube
True
Once OPC’s proliferate, they migrate to developing __ and ___ matter areas of the CNS before the differentiate into ________
white and gray matter; myelinating oligodendrocytes
True or False: Oligodendrocytes emerge from OPC’s during development
True
OPC’s (oligodendrocyte progenitor cells) are found in abundance in the adult CNS. What are their function here?
- Make new oligodendrocytes, which regenerate myelin lost during aging or disease
- Change pattern of myelination (CNS plasticity - generate new myelin during learning new motor activity)
How does neuronal activity affect myelination?
Induces OPC’s to proliferate and generate new myelin
True or False: During CNS myelination, oligodendrocytes extend a single process, which ensheaths and wraps around an axon, while also extending along length to form internodal region
False - during CNS myelination, oligodendrocytes extend MULTIPLE processes, which ensheath and wrap around an axon, while also extending along the length to form the internodal region
True or False: The internodal region is logated between the paranodes
True
Describe the myelin in the internodal region
Describe the myelin in the innermost layer
Internodal = Compact (w/o cytoplasm)
Innermost = Non-compact (with cytoplasm)
According to EM analysis, myelin is a multi-layered stack of thick membranes with periodic structure of alternating electron dense layers (known as: _____) and light layers (known as: ____)
Electron dense layers (of myelin) =
Major dense line
Electron light layers (of myelin) =
Intraperiod line
Why is compact myelin essential for saltatory AP propagation?
Provides HIGH electrical resistance and LOW capacitance
True or False: At the end of myelin, you would expect to see compacted myelin that terminates in the paranodal loops
False - at the end of myelin you would expect to see non-compacted regions.
However, myeline DOES terminate in the paranodal loops
In addition to paranodal loops, non-compact regions also comprise the outer and inner ______ “tongues” of myelin membranes
periaxonal
True or False: Cytoplasmic channels, which resemble Schmidt-Lanterman incisures, can also be found in the developing CNS myelins sheath and remain throughout the course of one’s lifetime
False - although cytoplasmic channels, which resemble Schmidt-Lanterman incisures, can also be found in developing CNS myelin sheath, they often DISAPPEAR once myelination is complete
How do oligodendrocytes and Schwann cells metabolically support axons?
- Provide them with lactate for ATP generation
- Regulating angiogenesis during development
Oligodendrites interact with the axon to organize the __ __ ____, which are essential for saltatory conduction
Nodes of Ranvier
True or False: M.S is a demyelinating disease caused by Schwann cell death
False - M.S is a demyelinating disease caused by OLIGODENDROCYTE death
Four features of MS?
1) Loss of myelin
2) Failure of myelin repair in CNS
3) Neuron dysfunction/axon degeneration
True or False: The Nodes of Ranvier contain Potassium channels
False - The Nodes of Ranvier contain Na channels (Na+)
True or False: The Nodes of Ranvier are myelinated segments of the axon
False - the Nodes of Ranvier are NON-myelinated segments of the axon
True or False: Without proper metabolic support provided by oligodendrocytes, ALS may develop
True
What are the most abundant cell type in the vertebrate CNS?
A. Schwann Cells
B. Oligodendrocytes
C. Macroglia
D. Neuroglia
E. Astrocytes
E. Astrocytes
What are the two types of astrocytes?
Protoplasmic and Fibrous
Where are protoplasmic astrocytes localized?
Where are fibrous astrocytes localized?
Protoplasmic = Gray matter
Fibrous = White matter
Protoplasmic astrocytes are highly ramified and their end feet contact __ ___; and they have terminal project that ensheathes ___
blood vessels; synapses
What are two specialized forms of astrocytes?
1) Muller glia (retina)
2) Bergmann glia (cerebellum)
What type of junction allows astrocytes to communicate with each other and with oligodendrocytes?
Gap junctions allow for metabolite exchange
What are seven functions of astrocytes in the CNS?
1) Neuronal survival
- take up nutrients in blood
2) Neurovascular coupling
- increases blood flow to brain regions with active neurons
3) Remove/recycle NT
4) Maintain BBB
- allows CNS blood vessels to regulate ion movement
5) Form, strengthen, and turnover synapses
- form and inhibit synapses
6) Pruning
- via phagocytosis
7) Control local synaptic activity
- respond to neuronal activity by increasing calcium waves
True or False: Only astrocytes eliminate synapses (prune)
False - both astrocytes and microglia prune synapses
What two cell types are implicated in Huntington’s Disease, Alzheimer’s, Parkinson’s, and ALS?
Microglia and astrocytes
During CNS damage and disease, astrocytes become activated and begin up-regulating ___ , undergoing ____, proliferation and migration.
This process is known as: ____
GFAP (glial fibrillary acidic protein) , hypertrophy
Reactive astrogliosis
What are the good and bad features of astrogliosis?
(+): can restrict inflammation/infection; preserve tissue structure/function
(-): glial scar formation - major barrier for CNS regeneration!
____ are the resident immune cells in the CNS that occupy the entire CNS parenchyma when they are resting cells and have a role in immune surveillance
A. astrocytes
B. macroglia
C. microglia
D. schwann cells
C. microglia
True or False: macroglia are involved in spatial patterning and synaptic wiring throughout the healthy, developing, adult CNS
False - MICROGLIA is involved in spatial patterning and synaptic wiring throughout the healthy, developing, adult CNS
Which two molecular signals are used by microglia to tag synapses for elimination?
C1q and C3
True or False: Microglia guide axons to their destination and promote precursor proliferation and survival
True
Targeting microglia with which drug during development will result in increased neuronal apoptosis in the cerebral cortex?
Minocycline
Fractalkine (also known as CX_CR_)—a chemokine made by neurons—may promote role of microglial cells
CX3CR1
Which cells are the only intrinsic brain cells that express receptors for CX3CR1?
Microglial cells
How do astrocytes indirectly prune?
How do astrocytes directly prune?
Indirect - induce expression of C1q and C3, recognized by microglia via TGF-B
Direct - recognized MEGF10 and MERTK
True or False: Microglia increase calcium concentration and generate calcium waves in response to neuronal activity
FALSE - ASTROCYTES increase calcium concentration and generate calcium waves in response to neuronal activity
Reactive astrocytes are found in ___ deposits in Alzheimer’s
alpha-beta deposits
Activated microglia are characterized by a change in morphologic phenotype, from highly ___ cell to an ___ cell
ramified ; amoeboid
What are the two types of microglial activation states?
M1 State: pro-inflammatory state
M2 State: related to repair
True or False: Microglia play a role in dead cell clearance and initiate cell death by producing ROS, TNF-a, glutamate
True
True or False: Microglia make trophic, mitogenic, and anti-inflammatory factors
True
