Glial cells Flashcards

1
Q

what are the 2 main pocket lineages of glial cell

A

microglia and macroglia

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2
Q

what are the four main functions of glial cells

A
  1. to surround neurons and provide physical support (hold them in place)
  2. to supply nutrients and oxygen to neurons (blood brain barrier)
  3. to insulate one neuron from another and facilitate synaptic communication
  4. to destroy and remove cell debris and unwanted molecules
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3
Q

what developmental roles do glia have

A

guiding migration of neurons in early development, and producing molecules that modify the growth of axons and dendrites

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4
Q

what roles do glia have as active participants in synaptic transmission

A

regulating clearance of neurotransmitter from cleft, releasing factors such as ATP which modulate presynaptic function and sometimes releasing neurotransmitter themselves

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5
Q

Glia are intimately correlated with ________. more advanced organisms -> more _______________.

A

Glia are intimately correlated with brain evolution. More advanced -> more percentage of brain is made out of glia

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6
Q

when were glial cells first noted and first named

A

First noted in 1824 and first named in 1856 (virchow)

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7
Q

the discovery of glial cells was credited to who

A

Rudolf Virchow

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8
Q

The first description of glia was by…

A

Rene Dutrochet

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9
Q

Otto Deiters claimed the defining feature of glial cells was what?

A

the lack of axons

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10
Q

who is Pio del Rio-Hortega

A

a student of Cajal, in 1920 classified the glia into four types: protoplasmic in gray matter, neuroglia in white matter, mesoblastic microglia, and interfascicular glia (what are now oligodendrocytes) – brought him a lot of trouble, he had to move.

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11
Q

what functions of glia cells were proposed by early neuroscientists and proved right

A
  • ability to secrete chemicals (Nageotte)
  • association with blood vessels (Golgi)
  • morphological plasticity (Cajal)
  • ability to electrically insulate (Cajal)
  • role in neurotransmitter uptake and termination (Lugaro)
  • role in pathology (Virchow).
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12
Q

which neuroglia are found in the peripheral nervous system

A

satellite cells, schwann cells

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13
Q

what neuroglia are found in the central nervous system

A

ependymal cells, oligodendrocytes, astrocytes, microglia

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14
Q

which glia originated from neuroectoderm

A

oligodendrocytes and astrocytes

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15
Q

which glial cells are derived from mesoderm/ yolk sac

A

microglia

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16
Q

which lineage of human mesenchymal stem cells do glia come from

A

myeloid

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17
Q

what are macroglia

A

the major supporting cells and include astrocytes, oligodendrocytes, and ependymal cells.

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18
Q

the endothelial blood brain barrier formation coincides with what?

A

the onset of vasculogenesis at 6 week of gestation

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19
Q

from 7 weeks gestations what features of the blood-CSF barrier are forms

A

show tight junctions similar to adult forms in many places (across choroid plexus, pia-arachnoid barrier and CSF-brain barrier)

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20
Q

what are radial glia

A

a common progenitor, they generate all types of glia. contribute to populating the brain and providing a scaffold for neuronal migration. they differentiate from neural progenitors early in development. somata in the ventricular zone and extending prolongations to the pia.

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21
Q

what does the key stage O2A progenitor give rise to

A

astrocytes and oligodendrocytes

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22
Q

what transcription factors control oligodendrocyte stepwise differentiation/maturation

A

notch1 and prox1

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23
Q

what is the precursor cell to oligodendrocytes

A

NG2 precursors

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24
Q

what major resident glial (precursor) cell population is retained throughout life

A

NG2 precursors

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25
Q

what cells give rise to schwann cell precursors

A

neural crest cells

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26
Q

what cells do neural crest cells give rise to

A

Schwann cell precursors, peripheral sensory and autonomic neurones and satellite cells of the dorsal root ganglia.

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27
Q

what determines whether immature schwann cells differentiate into myelinating or non myelinating cells

A

early association with large or small diameter axons (respectively)

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28
Q

what is wallarian degeneration

A

an active process of retrograde degeneration of the distal end of an axon that is a result of a nerve lesion (dedifferentiation of schwann cells is important) - two main causes 1) degenerative diseases affecting nerve cells, and 2) traumatic injury to the peripheral nerves.

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29
Q

what are key factors defining gliogenesis

A

Sox9 and NFIA

+ shh and notch

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30
Q

what is gliogenesis

A

the developmental process by which glial cells – astrocytes, oligodendrocytes, Schwann cells, microglia – are generated.

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31
Q

what are the two sites of constant neurogenesis

A

the lateral subventricular zone (SVZ) and the Dendate Gyrus of the hippocampus

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32
Q

what is the rostral migratory stream (RMS)

A

the major pathway by which progenitor cells migrate from the subventricular zone (SVZ) to the olfactory bulb (OB)

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33
Q

what protein is involved in astrocyte maturation

A

S100beta

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34
Q

what macrophage subpopulations are in the brain

A

microglial cell, meningeal macrophage, dendritic cell, choroid plexus macrophage, perivascular macrophage

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35
Q

what functions do microglial cells have

A

immunosurveillance, synaptic pruning, neuromodulation, phagocytosis

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36
Q

what are the two primary routes of microglial regulation of brain development

A

the release of diffusible factors and phagocytosis. phagocytize many products in the brain, including synaptic elements, living cells, dying or dead cells, and axons (remove excess cells (+in neurogenesis in adulthood) and excess synaptic contacts (up to 20yoa))

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37
Q

what two glial cells help regulate synaptic function

A

astrocytes and microglia

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38
Q

what are the basic characteristics of microglial population distribution

A

Ramified morphology, tiling the brain parenchyma in a mosaic-like distribution
Biggest differences in morphology between grey (ramified) and white (bipolar) matter
Variable densities in different regions, with each cell covering an average volume of 50000mm3

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39
Q

microglial repertoire of immune sensors and reactants allows…….

A

……rapid and plastic reactions to disruptions of the brains homeostasis

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40
Q

who was generally considered the father of microglia

A

Pio del Rio Hortega

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41
Q

what’s the location that perivascular microglial cells are derived showed by Hickey and Kimura in 1988

A

bone marrow

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42
Q

when did Franz Nissl develop Nissl staining

A

1880

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43
Q

where are the fountains of microglia described by Rio Hortega located

A

in the corpus callosum and other perinatal white matter

44
Q

what are erythromyeloid progenitors (EMPs)

A

arise from the yolk sac endothelium, just prior to vascular remodeling, and are the source of adult/post-natal tissue resident macrophages

45
Q

what specific markers do uncommitted EMPs express

A

CD31 and c-Kit

46
Q

what happens to amoeboid cells in the postnatal brain

A

amoeboid cells persist during the first 2 weeks of the postnatal brain where they gradually acquire the ramified shape characteristic of microglia in the steady state.

47
Q

what subset of master regulators help cooperatively drive specialisation and fate acquisition of EMPS into immature macrophages

A

PU.1, C/EBPs, RUNX1, and IRF8

48
Q

what are the functions of astrocytes

A
  • Neurogenesis and gliogenesis in the adult brain
  • Neuronal guidance in development: role of radial glia
  • Regulation of synaptogenesis and synaptic maturation in development?
  • Microarchitecture of the brain. Define and connect domains that include neurons, synapses and blood vessels.
  • Creation of the blood-brain barrier
  • Synaptic modulation
49
Q

astrocytes form local domains by connecting via ____________ so there is no need for extracellular communication components

A

gap junctions

50
Q

what are Bergmann cells

A

a unipolar astrocyte in the cerebellum, displaying a tight association with Purkinje cells

51
Q

how do astrocytes act as the third in the tripartite synapse

A

astrocytes are excitable cells: in response to pre/post synaptic stim they can produce transient changes in their intracellular Ca2+ concs and release Ca stores from ER
astrocytes communicate bidirectionally: able to detect neurotransmitters + other signals and can release their own NTs or gliotransmitters that can modify the electrophysiological excitability of neurons
Communication with other astrocytes modulating distant synapses

52
Q

what role do astrocytes have in glutamate transmission

A

participation in Glutamate clearance (by converting it into glutamine by glutamine synthetase (GS))
can drive synchronous depolarisation
modulate synaptic communication by gliotransmitters

53
Q

what are the ATP gliotransmitter receptors present in neurons and astrocytes

A

ATP targets P2X receptors, P2Y, and A1 receptors.

54
Q

what are the two major gliotransmitters

A

glutamate and ATP

55
Q

what functions does ATP have as a gliotransmitter

A

insertion of AMPA receptors into the postsynaptic terminal, paracrine activity through calcium waves in astrocytes, and suppression of synaptic transmission

56
Q

give an example of astrocytes response selectively in the hippocampal stratum oriens

A

Astrocytes of the hippocampal stratum oriens form tripartite synapses with axonal projections from the alveus.
The alveus projections can form either glutamatergic or cholinergic synapses with the stratum oriens, BUT the astrocytes of this region respond with changes in calcium concentration only to cholinergic activation of alveus projections
(do respond to Glu but only by synaptic activity originating from the Schaffer collateral)

57
Q

how are astrocytes involved in synaptic plasticity

A

astroglial release of glutamate, ATP, and cytokines likely alters the survivability and functioning of newly formed connections.

58
Q

how do astrocytes integrate and modulate info from their synaptic inputs

A

produce changes in their intracellular calcium concentrations that are non-linear with the strength of synaptic input.
are capable of producing either a potentiated calcium concentration response at low frequencies of stimulation or a depressed calcium concentration response at high frequencies of stimulation.

59
Q

when a lesion occurs on the spinal cord, what determines the severity of paralysis

A

the placement of the lesion - the higher up it is the more wide spread the paralysis as it prevents any downstream signaling

60
Q

what is a glial scar

A

a reactive cellular process (involving astrogliosis) formation of scar tissue around an injury to the central nervous system - causes interruption to neural repair and regrowth - a balance of support and inhibition

61
Q

what is the growth cone?

A

A growth cone is a large actin-supported extension of a developing or regenerating neurite seeking its synaptic target - drive actin growth

62
Q

what is the main cellular component of glial scars

A

reactive astocytes

63
Q

what potential mechanisms explain why transected axons fail to regrow spontaneously across severe tissue lesions

A

potential mechanisms include: (i) reduced intrinsic growth capacity of mature CNS neurons; (ii) absence of external growth stimulating and supporting factors; and (iii) presence of external inhibitory factors associated with myelin, fibrotic tissue or astrocytic scars

64
Q

how do atrocytes contribute to failure of axonal growth after central nervous system injury

A

they provide both physical and chemical distruption: generation of a capsule to contain the injury turns into a cystic cavity where debris like blood vessels etc is remove and the cavity is filled with cystic fluid. this is a physical inturruption that stops regrowth
release of chemcials that interupt axonal growth include CSPGs

65
Q

what chemcials contribute to the potential of astrocytes to help axonal regrowth after glial scar formation

A

Integrin, Laminin, N cadherin

66
Q

injection of what two proteins in hydrogel has been shown to promote aconal guidence and activation of more protective atrocytes

A

neurotrophin-3 and BDNF

67
Q

what is the first defence when the central nervoys system is injured

A

astrocytes increase in nymber and change morphology and produce fribrotic tissue to try and ocntain the injury

68
Q

removal of what protein could allow for spontaneou dregeneration of axons

A

pTEN

69
Q

what are the myelination cells of the nervous sytem what are two major differences

A
Oligodendrocytes (all myelination) in CNS, each myelinating multiple axons (average 10 axons per cell)
Schwann cells (myelinating and non myelinating), each wrapping aorund a single cell
70
Q

myelination is dependent on ______ (visaversa)

A

axonal diameter

71
Q

what is a pneumbra in neuroscience

A

the penumbra is the part of the brain that is sandwiched between brain regions committed to die and those that receive enough blood to communicate. Therefore, it is ischemic brain tissue that has just enough energy to survive for a short time but not enough to communicate and function

  • reversibly injured brain tissue around ischemic core
72
Q

the ___________ of axon (diameter) and the _________ (number of lamellae) are intedependent, resulting in the _____ of axons

A

The radial growth of axons (axon’s diameter) and the myelin sheath (number of lamellae) are interdependent, resulting in the g-ratio of axons (1:10)

73
Q

what is the g ratio of axons and what is the optimal ratio

A

ratio of the inner axonal diameter to the total outer diameter -a functional and structural index of optimal axonal myelination.
0.6

74
Q

describe the interdepedence of glia and axons

A

the loss of axons results in degeneration of oligodendrocytes and de-differentiation of Schwann cells; conversely, axons degenerate in the absence of appropriate support from Schwann cells and oligodendrocytes

75
Q

what are non-myelinating schwann cells (what markers do they possess not found on myelinating schwann cells)

A

Surround bundles of small-diameter neurons
Provide support and isolation from myelinated axons
Express specific surface markers L1 and NCAM not found in myelinating Schwann cells

76
Q

what are perisynaptic schwann cells (teloglia)

A
(at NMJ) ensheath terminal axonal boutons
function in synaptic transmission, synaptogenesis and nerve regeneration
77
Q

how do perisynatpic schwann cell repsond and modulate synaptic transmission at NMJs

A

They respond to synaptic activity by Ca2+ waves
Able to modulate synaptic activity by regulating extracellular ion levels and also inducing post-synaptic Ach receptor aggregation

78
Q

what are olfactory bulb ensheathing cells (OBECs)

A

(similar to non myelinating schwann cells) ensheath axons of the olfactory nerve - located in the interphase of the CNS and PNS

79
Q

what do olfactory bulb ensheathing cells do

A

 They phagocytose axonal debris and dead cells
 OBECs support and guide olfactory axons, grow through glial scars, and secrete many neurotrophic factors
 OBECs express glial markers such as GFAP, s100, and p75, and radial glial markers such as nestin and vimentin

80
Q

what is the myelin sheath

A

 Fatty insulated later that facilitates saltatory conduction
wrapped around axons in concentric layer called lamellae. longitudinally separated by nodes of Ranvier (myelin between nodes are the internodes)

81
Q

what is the composition of the myelin sheath

A

 Lipids constitute 70% of myelin, with cholesterol being the main component, with phospholipids and glycolipids (ratio 4:3:2)
 Rich in glycosphingolipids, mainly GalC
 Proteins constitute 30%, mostly shared CNS vs PNS

82
Q

what are the difference in composition between CNS and PNS myelin sheath

A

Composition of gangliosides differs; in CNS=GM4 PNS=LM1, GM3
Main CNS proteins are MBP and PLP
Main PNS protein is P0 and PMP22 and Cx32

83
Q

what do MBP and PLP do in the CNS myelin sheath

A

fuse the extracellular and cytoplasmic faces

84
Q

what does P0 do in the PNS

A

mediates fusion of lamellae

85
Q

what is MAG and where is it found

A

In the myelin sheath of both the PNS and CNS - a protein important for myelin-axon interaction binding to specific gangliosides on the axonal surface

86
Q

what are the four phases of myelination

A

Axon contact
Axon ensheathment and establishment of internodal segments
Remodelling
Maturation

87
Q

what occurs during the first stage of myelination?

A

if axon grows thicker than 0.7mm (PNS) or 0.2mm (CNS)
Loss of NCAM from axonal surface triggers myelination
Contact with axons triggers differentiation of OPCs into Oligodendrocytes starting to express myelin products (GalC, CNP, MBP etc)

88
Q

what protein tags axons to be myelinated (‘ready for myelination’)

A

L1 expressed premyelination and tags axons to be myelinated

89
Q

what occurs during phase two of myelination

A

Axon ensheathment and establishment of internodal segments

Extension of an initiator process that spirals along the axon (using MAG and PLP to “stitch”)
adhesion/ recognition signals
Myelination of multiple axons
Initial clustering of Na+ channels at nodes of Ranvier

90
Q

what occurs during the third and fourth stages of myelination

A

Remodeling and maturation
Subsequent wraps of myelin are produced, which fuse to each other dependent on PLP and MBP
Loss of nonmyelinating processes
Maturation of nodes of Ranvier (synchronised expression of molecular pairs at axon and myelin)
Myelin compaction - radial and longitudinal growth

91
Q

what three things drive the pathophysiology of multiple sclerosis

A

Autoimmunity: generation of autoantibodies against myelin components, commonly involves white matter and direct damage of oligodendrocytes causing demyelination (remyelination in early phase but not complete (relapse leads to impaired remyelination)

BBB breakdown: damage drives entrance of immune cells predominantly T cells

Chronic inflammation: demyelination triggers T cell attack of myelin, driving recruitment of other inflammatory cells by releasing cytokines and antibodies.
BBB leakage causes swelling, activation of macrophages and a vicious cycle of inflammation and damage driven by astrocytes and glia

92
Q

what role do glia play in multiple sclerosis

A

astrocytes recruit lymphocytes and cause tissue damage (gliosis of glial scar)
microglia cause degeneration of chronically demyelinated axons, redistribute sodium channels and remyelinate after demyelination and axonal transduction (also cause axonal transduction

93
Q

what is microglial surveillance

A

microglia to swarm to the area of injury immediately
React immediately, first line of defense. Extend processes towards the injury. If bad enough they will proliferate around it. Preserve neurons by keeping them away from the injury

94
Q

what three ways can microglia vary

A

 Morphological diversity
 Regional density
 Different turnover rates

95
Q

what is the difference in microglial populations between humans and mice

A

In humans more microglia in white matter than grey matter, the same ratio across the brain
In mouse more in grey than in white. Some regions have higher turnover rates than other

96
Q

what three general roles do microglia have in multiple sclerosis

A

phagocytosis of myelin, antigen presentation to T cells and release of proinflammatory cytokines in active lesions

97
Q

what are the two main function of microglia

A
  • Ability of microglia to remove synapse: whole/bits? Not sure. Evidence for eating synapses
  • Ability to phagocytose whole dead cells, clear excess of apoptopic cells. Before it becomes toxic
98
Q

what are the five subpopulations of microglia

A
surveillant microglia
proliferating microglia
pruning microglia
neuromodulatory microglia
phagocytic microglia
99
Q

what are the two types of microglia lineage determining transcription factors are there that cause diversity in microglia

A

environment-dependent factors and core macrophage factors

100
Q

what role do microglia have in the development of neural connections throughout the dorsal lateral geniculate nucleus in development

A

• Retinal ganglion cells (RGCs) form synaptic connections with relay neurons throughout the dorsal lateral geniculate nucleus (dLGN) of the thalamus
• During the postnatal pruning period, RGC synaptic inputs originating from the same eye as well as between eyes compete for territory throughout the dLGN
- Microglia with remove projections from the ipsolateral side (so that the contralateral connections remain)

101
Q

perturbation of microglia activity into the wiring of early forebrain development affects the…

A

(cell depletion or cx3cr1−/−, CR3−/−, DAP12−/−) affects the outgrowth of dopaminergic axons in the forebrain and the laminar positioning of subsets of neocortical interneurons

102
Q

what cells control apoptotic cell clearance in developing brain

A

microglia cause significant death of progenitors and the extra neurons made during development

103
Q

what triggers the specification of disease-associated microglia from the homeostatic state

A

trem2

104
Q

what is involved in the development of Alzheimers disease

A

innate immunity (genes fromcomplemetn pathway) drives alzheimers disease as well as dramatic phenotypic change of microglia to disease associated microglia by trem2

105
Q

what factor is the main driver of microglial proliferation causing Prion disease, ALS and FTD - and it a potential target for treatment

A

CSF1

- targetting may prevent neurodegeneration and behaviour

106
Q

what progenitors do microglia develop from

A

yolk sac progenitors in a stepwise program

107
Q

what are the major roles of microglia

A

development of the brain, surveillant/homeostatic profile, synaptic modulation, brain immunity