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ANAT365 > Module 11 - Microglia > Flashcards

Module 11 - Microglia Flashcards

1
Q

how many more glia are there compared to neurons?

A

10-50x more glia than neurons

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2
Q

what are the 4 classes of glial cells?

A
  1. Astrocytes (derived from neuroepithelium)
  2. Microglia (related to macrophages, mesodermal)
  3. Oligodendrocytes (CNS, derived from neuroepithelium)
  4. Schwann Cells (PNS, derived from neuroepithelium, neural crest)
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3
Q

which type of glial cells are myelinated?

A

oligodendrocytes and schwann cells

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4
Q

what’s the difference between CNS and PNS?

A

CNS is enveloped in bone, the PNS is not

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5
Q

what are astrocytes?

A

star shaped cells with end-feet that contact capillaries or neurons; part of the blood-brain barrier

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6
Q

what is astrocytes function?

A

bring nutrients into the CNS and to prevent the entry of many compounds into the CNS

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7
Q

what chemical’s extracellular levels are controlled by astrocytes?

A

potassium; astrocytes can take up lots of potassium released by neuronal activity

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8
Q

astrocytes are the only cell type that can store what molecule?

A

glycogen; it can supply neurons with glucose and lactate

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9
Q

what can astrocytes supply neurons with?

A

glucose and lactate

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10
Q

name a marker for astrocytes

A

GFAP: glial fibrilary acid protein

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11
Q

what does myelin provide to cells?

A

electrical insulation wrapped around the axons

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12
Q

what kind of animals have myelin?

A

vertebrates only!

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13
Q

are dendrites myelinated?

A

no; only axons (not all axons tho)

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14
Q

what are nodes of ranvier?

A

highly specialized region of the axonal membrane that is not myelinated

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15
Q

what is concentrated at node of ranvier? why?

A

Voltage gated sodium channels: they regenerate APs between myelin sheath

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16
Q

how long are each segments (one Schwann cell) of myelin along a peripheral nerve?

A

about 1mm long

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17
Q

what is a oligodendrocyte?

A

CNS Myelinating Glia

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18
Q

what is different between Schwann cell and oligodendrocyte?

A

oligodendrocyte (CNS) can myelinate multiple axons simultaneously

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19
Q

how many axons are myelinated per one oligodendrocyte approximately?

A

15 axons

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20
Q

how long can internode be?

A

varies: from 10s of microns to 100 microns

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21
Q

are all oligodendrocytes myelinating?

A

no; there are many perineural non-myelinating oligodendrocytes

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22
Q

how was the existence of oligodendrocytes proved?

A

via staining techniques that selectively visualized these cells

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23
Q

Where do Schwann cells come from?

A

Neural crest: Born in neural epithelium and migrate out of the neural tube (CNS) to myelinate axons in peripheral nervous system (PNS).

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24
Q

Where do Oligodendrocytes come from?

A

Born as oligodendrocyte precursor cells (OPCs) in the ventricular zone at several places along the neural tube, and then migrate and proliferate to populate all myelinated regions of the CNS.

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25
Q

more precisely what are the steps of oligodendroglial development in
the mammalian spinal cord?

A
  1. OPCs born in ventricular zone
  2. OPC migration
  3. OPC proliferation
  4. Differentiation to post-mitotic but pre-myelinating oligodendrocytes
  5. Establishment of contact with axons, myelin formation and elimination of superfluous oligodendrocytes by apoptosis.
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26
Q

what happens to not yet mature oligodendrocytes that don’t contact an axon?

A

they die

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27
Q

where do OPCs migrate to?

A

to where there are most axons

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28
Q

what is PDGFalphaR?

A

platelet derived growth factor receptor: unique OPC marker

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29
Q

where are OPCs born?

A

ventral midline of the embryonic spinal cord, just dorsal to the floor plate.

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30
Q

in what directions do OPCs migrate to after their birth?

A

migrate dorsally away from the floor plate (FP)

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31
Q

what are netrins?

A

Secreted Chemotropic Guidance Cues for Cell and Axon migration (direct axon migration during neural development)

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32
Q

what proteins are netrins related to?

A

laminins

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33
Q

where is netrin-1 found?

A

it is made in the floor plate at the ventral midline and is secreted to form a ventral to dorsal gradient

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34
Q

what are netrins vs laminins average size?

A

netrins are 75kDa,
laminins are 800 kDA

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35
Q

netrin secretion makes the ECM _______

A

polarized

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36
Q

what are the 2 netrin receptors families and their function?

A

DCC: attraction to netrin-1 (growing towards netrin gradient)
UNC5: (homologs A-D) required for repulsion to netrin-1 (growing away from netrin)

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37
Q

do OPCs express netrin-1? what do they express?

A

no; they express DCC and/or UNC5A & B (netrin receptors)

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38
Q

what happens to cells that make both DCC and UNC5?

A

they have the capacity to respond to netrin-1 as an attractant or a repellent

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39
Q

how do netrin direct axon migration? what else do they influence?

A
  • via cytoskeletal organization
  • influence cell-substrate and cell-cell adhesion
40
Q

Netrin-1 repels oligodendrocyte precursor cells away from the _____ _______ directing them toward _____

A

ventral midline;
axons (future white matter)

41
Q

name other extracellular guidance cues that direct OPCs migration

A

long or short-range repellents, long or short-range attractants

42
Q

where are sodium channels concentrated?

A

at the node (between myelinated internode)

43
Q

where are potassium channels found?

A

in the juxtaparanode (under compact myelin)

44
Q

where is Caspr located?

A

at the paranode on the axonal surface

45
Q

what is the major axis of polarization of a myelinating glial cell?

A

the cell-body verses the myelin membrane

46
Q

the myelin sheath is sub-divided in what kind of regions?

A

compact and non-compact membrane regions

47
Q

what does MBP mark?

A

compact myelin membrane (internode)

48
Q

what is TMEM10 a marker for?

A

(type 1 transmembrane protein); not associated with compact myelin

49
Q

explain the myelin formation process

A

generation of the spiral wrap of the membrane (inner tongue wraps around);
compaction of myelin

50
Q

what is the g-ratio? what is the optimal value?

A

axon diameter / total outer diameter;
normal (optimal) = 0.6-0.8

51
Q

how is g-ratio maintained?

A

ticker axons have ticker myelin

52
Q

describe myelin composition

A

similar to PM; 80% lipid, 20% proteins, high cholesterol and glycolipids

53
Q

what is sphingomyelin composed of?

A

sphingosine (lipid) and phosphocholine (hydrocarbon and nitrogen)

54
Q

what chain strengthens myelin?

A

sphingomyelin hydrocarbon chains extending from the lipid bilayer

55
Q

what did the synthetic fiber experiment show?

A

oligodendrocytes will make myelin wraps even without a living axon!

56
Q

what does it mean that oligodendrocytes myelinate even a synthetic fiber?

A

they don’t need a specific signal to form compacted myelin

57
Q

what is PMP22 responsible for?

A

it is the genetic basis for Charcot Marie tooth disease

57
Q

describe myelin structure

A

compacted lipid bilayer

58
Q

where is MBP found?

A

intracellular face of the PM; it is membrane-associated

59
Q

what is MBP function?

A

zipping the cytoplasm; bring the 2 membranes together, acting like a molecular bridge

60
Q

what % of myelin proteins are MBP?

A

30%

61
Q

what % of myelin proteins are PLP?

A

50%

62
Q

what is PLP role?

A

linking and compacting the extracellular face of the plasma membrane

63
Q

where is PLP translated?

A

at the rER

64
Q

where is PLP located?

A

it is stored in late endosomal compartment until it is recruited to the PM after trigger from contact with an axon

65
Q

where is MBP translated? why?

A

locally near its point of insertion in the PM; this prevents inappropriate membrane compaction

66
Q

what is multiple sclerosis caused by?

A

abnormal myelin, leading to decrease in axon conduction velocity and major disruptions of neuronal function in the brain

67
Q

what happens when you inject MBP into a mouse?

A

experimental allergic encephalomyelitis (EAE), characterized by loss of CNS myelin due to a immune response against MBP (experimental model of multiple sclerosis)

68
Q

what is the shiverer mouse?

A

a mouse with a deletion mutation of the MBP gene that produces tremors, convulsions, early death

69
Q

how can the shiverer mouse’s phenotype be rescued?

A

transgenic addition of a copy of the MBP gene

70
Q

what happens to PMP22 in CMT (charcot-marie-tooth)?

A

it is duplicated (increase in gene dosage)

71
Q

what are CMT disease characteristics?

A

cycles of demyelination and remyelination, weakness, greatly decreased conduction velocity in the peripheral nerves

72
Q

when does myelination start?

A

post birth

73
Q

why do we have myelin precursor cell our whole life?

A

because we add and loose myelin throughout our life

74
Q

what are Leukodystrophies?

A

A group of genetic disorders that effects the development and maintenance of myelin

75
Q

what happened when they transplanted human OPCs in an immunodeficient shiverer mice?

A

MBP came back and myelination was rescued

76
Q

what are microvilli specific to?

A

specific to schwann cells, found at node of ranvier

77
Q

are schwann cells or oligodendrocytes bigger?

A

schwann cells are 10x bigger

78
Q

what is found at the dynamic leading edge of a schwann cell?

A

F-actin

79
Q

describe the process of Caspr spiral consolidation

A

asymetric process; fronts of 2 schwann cells extend towards eachother, forming a spiral that disappears in mature node

80
Q

what proteins do NA but not K channels bind?

A

ankyrin

81
Q

what junctions are involved in anchoring paranodal loops to the axon and to eachother?

A

gap, thigh junctions between the myelin loops.
axo-glial adhesions between the paranodal channels and the axon

82
Q

what is the axo-glial adhesion junction made of?

A

Caspr, CNTN1 (contactin), NF155 (Neurofascin155)

83
Q

what happens after genetic deletion of caspr, NF155 or CNTN?

A
  • disruption of paranodal junctions and disorganization of the specialized domains along axons: no more boundary between paranode and juxtaparanode and node
  • balance and coordination deficit
  • reduced conduction velocity
84
Q

what kind of junctions do tight and gap junctions form between paranodal loops?

A

autotypic junctions

85
Q

what is claudin 11?

A

tight junction protein also called OSP oligodendrocyte specific protein

86
Q

what happens if you KO DCC? what does this show?

A

disruption of paranode maintenance; DCC is required to maintain axoglial parnodal junctions in the mature CNS

87
Q

what happens to Caspr in DCC KO?

A

Caspr distribution slides along the axon

88
Q

what happens to Na+ and K+ channels in netrin and DCC KO?

A

abnormal distribution

89
Q

how does selective deletion work? what was it used for?

A

selectively deleting floxed DCC allele in oligodendrocytes with tamoxifen regulated cre-recombinase

90
Q

what did DCC tamox induced deletion show?

A

paranode disruption aka DCC is essential for paranode

91
Q

what does UNC5B deletion cause?

A

everted paranodal loops, reduced claudin 11 levels, disruption of junction between loops

92
Q

what structures are made of non-compacted myelin?

A

Paranodal loops, Cajal Bands and Schmidt-Lantermann Incisures

93
Q

what are Cajal bands and S-L incisures for?

A

traverse compact myelin to connect cell body cytoplasm with the paranodal loops

94
Q

what does loss of Periaxin do?

A

loss of cajal bands, reduced internode length, slower conduction rate -> severe PNS demyelination neuropathy

95
Q

where is periaxin found?

A

at the junction of compact myelin and PM

96
Q

what organelle can travel through myelin via cytoplasmic channels?

A

mitochondria (cus they can divide and fuse, also channel can enlarge)

ANAT365 (10 decks)

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