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Human Neuroscience > L2: Cell Biology of Glia > Flashcards

L2: Cell Biology of Glia Flashcards

1
Q

___ are the non-neuronal supporting cells of the nervous system

A

Glia

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2
Q

Which nervous system do astrocytes, oligodendrocytes, and microglia belong to?

A

CNS

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3
Q

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

A

myelin sheaths

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4
Q

Macroglia includes: ___ and ____ lineage cells

A

astrocytes, oligodendrocyte lineage cells

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5
Q

Macroglia (as well as astrocytes and oligodendrocytes) are all derived from _____ in the embryonic neural tube and forebrain

A

NPC’s (neuroepithelial progenitor cells)

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6
Q

What do neuroepithelial progenitor cells (NPC’s) transform into?

A

Radial Glia

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7
Q

What cell type is the primary progenitor cells for both neurons and macroglia during embryogenesis?

A

Radial Glia

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8
Q

After radial glial cells generate neurons, ____ occurs and they begin differentiating into ____ or ____

A

Gliogenic Switch

1) Astrocytes
2) Oligodendrocyte Progenitor Cells (OPC’s)

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9
Q

Where are the Schwann cells in the PNS derived from?

A

Neural Crest

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10
Q

True or False: Microglia are endodermal in origin

A

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)
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11
Q

Schwann cell precursors originate from ____

A

NCC’s (neural crest cells)

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12
Q

Schwann cell precursors migrate out of the ganglia and into the ____, where they continue to proliferate and differentiate into ______

A

peripheral nerves; immature Schwann cells

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13
Q

Immature Schwann cells envelop groups of axons before terminally differentiating into either: ____ or _____ cells

A

Myelinating or Non-myelinating (Remak) Schwann Cells

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14
Q

When does radial sorting occur in Schwann cell development?

A

During differentiation into myelinating or non-myelinating schwann cells

  • Involves segregation to become individually ensheather and myelinated by myelinating Schwann cells
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15
Q

The non-myelinating Schwann cells bundle multiple smaller diameter unmyelinated axons into ___ ___

A

Remak Fibers

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16
Q

Schwann cells are surrounded by a ____ ___, a structure that supports nerve and guides axonal regeneration after peripheral nerve injury

A

basal lamina

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17
Q

What determines the phenotypic differentiation of Schwann cells to become either myelinating or non-myelinating cells?

A

The axon

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18
Q

True or False: Schwann cells contribute to the survival, guidance, and differentiation of axons, as well as their architecture and distribution of ion channels

A

True

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19
Q

Describe the stage of Schwann cell differentiation

A
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20
Q

True or False: Myelinated astrocytes are highly polarized cells, longitudinally and radially

A

False - myelinating schwann cells are highly polarized longitudinally and radially

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21
Q

What are the four ways in which myelinating Schwann cells are longitudinally organized?

A

1) Nodally
2) Paranodally
3) Juxtaparanodally
4) Internodally

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22
Q

True or False: The paranodal domain is the largest longitudinal domain of the myelinating schwann cell

A

False - the internodal domain is the largest, makes up the length of the Schwann cel

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23
Q

What is another name for the nodal region of the myelinated Schwann cell?

A

Node of Ranvier

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24
Q

The Node of Ranvier contains sodium channels and an assembly of proteins. What do these structures facilitate?

A

Saltatory propagation of action potential

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25
Q

Radially, Schwann cells are organized into an inner and outer compartment, which are known as?

A

Inner = Adaxonal
Outer = Abaxonal

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26
Q

Which radial compartment (the adaxonal or the abaxonal) of the schwann cell mediates interactions w basal lamina and contains the nucleus?

A

Abadxonal domain

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27
Q

What is located between the adaxonal and abaxonal domains?

A

Compact myelin sheath, composed by lamellae (many layers of the schwann cell membrane)

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28
Q

How many myelin internodes are formed by a single schwann cell?

How many myelin sheaths are formed by a single oligodendrocyte?

A

One

Dozens of myelin sheaths in the CNS

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29
Q

True or False: The myelin of an oligodendrocyte is often thicker than CNS myelin

A

True

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30
Q

True or False: Myelin is a low resistance and high capacitance membrane that is essential for saltatory propagation of the AP

A

False - while myelin is essential for saltatory propagation of the AP, it is high resistance and low capacitance

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31
Q

Compact myelin is interrupted by ____ incisures

A

Schmidt-Lanterman Incisures (located along internode and retain cytoplasm)

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32
Q

_______: clefts considered as channels for communication between inner and outer collars of cytoplasm via: gap junctions (formed b/w adjacent membranes)

A

Schmidt-Lanterman Incisures

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33
Q

In adult nerves, the fiber is covered by a collagen-rich and vascularized extracellular matrix known as the ____

A

Endoneurium

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34
Q

True or False: The endoneurium covers the basal lamina that surrounds the axon-Schwann cell unit

A

True

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35
Q

Groups of axons-Schwann cell units are bundled together as ____ via a muli-layered tube known as the ____

A

nerve fascicles; perineurium

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36
Q

___: the fibrous and dense coat the covers the external portion of nerves and fills the spaces between nerve fascicles

A

Epineurium

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37
Q

What are the two main types of peripheral nerve injuries?

A

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

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38
Q

True or False: Neurotmesis usually has very efficient recovery and is modeled by nerve crush in rodents

A

False - neurotmesis usually has a very POOR recovery and is modeled by nerve CUT in rodents

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39
Q

Axonotmesis has very ___ recovery and is modeled by nerve ___ in rodents

A

efficient; crush

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40
Q

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

A

regeneration units

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41
Q

Describe Neutromesis:

A
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42
Q

In the nerve cut (as occurs in neutromesis) - why is functional nerve recovery usually poor?

A

Targeting errors or regenerating axons that occurs at interphase (between proximal and distal nerve stumps)

43
Q

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

A

Wallerian Degeneration

44
Q

How do schwann cells behave differently than oligodendrocytes s/p peripheral nerve injury?

A

Schwann cells TRANSDIFFERENTIATE to clear cellular debris + coordinate repair

45
Q

True or False: Oligodendrocytes respond fast to peripheral nerve injury by proliferating and transdifferentiating from myelinating to nonmyelinated or immature oligodendrocyte cells

A

False - SCHWANN cells respond fast to peripheral nerve injury by proliferating and transdifferentiating from myelinating to non-myelinated or immature SCHWANN cells

46
Q

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

A

c-Jun

47
Q

True or False: c-Jun is rapidly upregulated in Schwann cells present anterior to the nerve injury

A

FALSE - c-Jun is rapidly upregulated in Schwann cells present DISTAL to the nerve injury

48
Q

____ are the predominant repair Schwann cells in the distal nerve stump and support nerve repair process

A

Bungner Schwann Cells

49
Q

Repair (Bungner) Schwann cells form the regeneration tracks, also known as the: ____

A

Bands of Bungner

50
Q

What are four ways in which Repair (Bungner) Schwann cells in the distal nerve stump support nerve repair process?

A

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

51
Q

True or False: Bands of Bungner are composed of elongating bipolar Schwann cells

A

True

52
Q

What disease can arise if there is mutation in several myelin or gap junction proteins expressed in myelinating schwann cells?

A

Charcot-Marie-Tooth Disease

53
Q

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

A

True

54
Q

True or False: Disruption of Schwann cell-neuronal interaction may cause the neuronal loss, as seen in Charcot-Marie-Tooth Disease

A

True

55
Q

True or False: Demyelination in CMT leads to axon degeneration, neuron loss, and conduction block

A

True

56
Q

True or False: Oligodendrocytes lineage cells arise from the neuroepithelial progenitor cells (NPC’s) of the embryonic neural tube and forebran

A

True

57
Q

Neuroepithelial progenitor cells (NPC’s) transform into radial glial, which are progenitor cells for both ___ and ___ (e.g astrocytes and oligodendrocytes)

A

neurons; macroglia

58
Q

Oligodendrocyte progenitor cells (OPC’s) are also known as ___ cells

A

NG2 cells (since they express this proteoglycan on their surface)

59
Q

True or False: OPC’s emerge from radial glial and arise from ventricular zones of the embryonic neural tube

A

True

60
Q

Once OPC’s proliferate, they migrate to developing __ and ___ matter areas of the CNS before the differentiate into ________

A

white and gray matter; myelinating oligodendrocytes

61
Q

True or False: Oligodendrocytes emerge from OPC’s during development

A

True

62
Q

OPC’s (oligodendrocyte progenitor cells) are found in abundance in the adult CNS. What are their function here?

A
  1. Make new oligodendrocytes, which regenerate myelin lost during aging or disease
  2. Change pattern of myelination (CNS plasticity - generate new myelin during learning new motor activity)
63
Q

How does neuronal activity affect myelination?

A

Induces OPC’s to proliferate and generate new myelin

64
Q

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

A

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

65
Q

True or False: The internodal region is logated between the paranodes

A

True

66
Q

Describe the myelin in the internodal region

Describe the myelin in the innermost layer

A

Internodal = Compact (w/o cytoplasm)

Innermost = Non-compact (with cytoplasm)

67
Q

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: ____)

A

Electron dense layers (of myelin) =
Major dense line

Electron light layers (of myelin) =
Intraperiod line

68
Q

Why is compact myelin essential for saltatory AP propagation?

A

Provides HIGH electrical resistance and LOW capacitance

69
Q

True or False: At the end of myelin, you would expect to see compacted myelin that terminates in the paranodal loops

A

False - at the end of myelin you would expect to see non-compacted regions.

However, myeline DOES terminate in the paranodal loops

70
Q

In addition to paranodal loops, non-compact regions also comprise the outer and inner ______ “tongues” of myelin membranes

A

periaxonal

71
Q

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

A

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

72
Q

How do oligodendrocytes and Schwann cells metabolically support axons?

A
  1. Provide them with lactate for ATP generation
  2. Regulating angiogenesis during development
73
Q

Oligodendrites interact with the axon to organize the __ __ ____, which are essential for saltatory conduction

A

Nodes of Ranvier

74
Q

True or False: M.S is a demyelinating disease caused by Schwann cell death

A

False - M.S is a demyelinating disease caused by OLIGODENDROCYTE death

75
Q

Four features of MS?

A

1) Loss of myelin
2) Failure of myelin repair in CNS
3) Neuron dysfunction/axon degeneration

76
Q

True or False: The Nodes of Ranvier contain Potassium channels

A

False - The Nodes of Ranvier contain Na channels (Na+)

77
Q

True or False: The Nodes of Ranvier are myelinated segments of the axon

A

False - the Nodes of Ranvier are NON-myelinated segments of the axon

78
Q

True or False: Without proper metabolic support provided by oligodendrocytes, ALS may develop

A

True

79
Q

What are the most abundant cell type in the vertebrate CNS?
A. Schwann Cells
B. Oligodendrocytes
C. Macroglia
D. Neuroglia
E. Astrocytes

A

E. Astrocytes

80
Q

What are the two types of astrocytes?

A

Protoplasmic and Fibrous

81
Q

Where are protoplasmic astrocytes localized?

Where are fibrous astrocytes localized?

A

Protoplasmic = Gray matter

Fibrous = White matter

82
Q

Protoplasmic astrocytes are highly ramified and their end feet contact __ ___; and they have terminal project that ensheathes ___

A

blood vessels; synapses

83
Q

What are two specialized forms of astrocytes?

A

1) Muller glia (retina)
2) Bergmann glia (cerebellum)

84
Q

What type of junction allows astrocytes to communicate with each other and with oligodendrocytes?

A

Gap junctions allow for metabolite exchange

85
Q

What are seven functions of astrocytes in the CNS?

A

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

86
Q

True or False: Only astrocytes eliminate synapses (prune)

A

False - both astrocytes and microglia prune synapses

87
Q

What two cell types are implicated in Huntington’s Disease, Alzheimer’s, Parkinson’s, and ALS?

A

Microglia and astrocytes

88
Q

During CNS damage and disease, astrocytes become activated and begin up-regulating ___ , undergoing ____, proliferation and migration.

This process is known as: ____

A

GFAP (glial fibrillary acidic protein) , hypertrophy

Reactive astrogliosis

89
Q

What are the good and bad features of astrogliosis?

A

(+): can restrict inflammation/infection; preserve tissue structure/function

(-): glial scar formation - major barrier for CNS regeneration!

90
Q

____ 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

A

C. microglia

91
Q

True or False: macroglia are involved in spatial patterning and synaptic wiring throughout the healthy, developing, adult CNS

A

False - MICROGLIA is involved in spatial patterning and synaptic wiring throughout the healthy, developing, adult CNS

92
Q

Which two molecular signals are used by microglia to tag synapses for elimination?

A

C1q and C3

93
Q

True or False: Microglia guide axons to their destination and promote precursor proliferation and survival

A

True

94
Q

Targeting microglia with which drug during development will result in increased neuronal apoptosis in the cerebral cortex?

A

Minocycline

95
Q

Fractalkine (also known as CX_CR_)—a chemokine made by neurons—may promote role of microglial cells

A

CX3CR1

96
Q

Which cells are the only intrinsic brain cells that express receptors for CX3CR1?

A

Microglial cells

97
Q

How do astrocytes indirectly prune?
How do astrocytes directly prune?

A

Indirect - induce expression of C1q and C3, recognized by microglia via TGF-B

Direct - recognized MEGF10 and MERTK

98
Q

True or False: Microglia increase calcium concentration and generate calcium waves in response to neuronal activity

A

FALSE - ASTROCYTES increase calcium concentration and generate calcium waves in response to neuronal activity

99
Q

Reactive astrocytes are found in ___ deposits in Alzheimer’s

A

alpha-beta deposits

100
Q

Activated microglia are characterized by a change in morphologic phenotype, from highly ___ cell to an ___ cell

A

ramified ; amoeboid

101
Q

What are the two types of microglial activation states?

A

M1 State: pro-inflammatory state
M2 State: related to repair

102
Q

True or False: Microglia play a role in dead cell clearance and initiate cell death by producing ROS, TNF-a, glutamate

A

True

103
Q

True or False: Microglia make trophic, mitogenic, and anti-inflammatory factors

A

True

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