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UNI Y2: Physiology & Pharmacology of the CNS > Lecture 2: Intro to Glia Cells > Flashcards

Lecture 2: Intro to Glia Cells Flashcards

1
Q

what are the two major classes of cells in the brain?

A
  • neurons
  • glia
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2
Q

explain the distinction between neurons and glia cells

A
  • neurons electrically excitable, glia electrically non-excitable
  • neurons respons to external stimuli by generating action potential (AP), glia unable to generate an AP
    (note: neurons capable of propagating through neuronal network)
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3
Q

state one feature all neuroglia share?

A

all the homeostatic cells of the NS (PNS & CNS)

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4
Q

state the main types of glia in the CNS

A

CNS:
macroglia (ectodermal/neural origin) & microglia (mesodermal/non-neural origin)

within macroglia:
astroglia, NG2(expressing)-glia and oligodendroglia

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5
Q

state the main types of cells in th PNS

A
  • Schwann cells (myelinating, non-myelinating or perisynaptic)
  • Olfactory ensheathing cells
  • satellite glial cells
  • enteric glia (glia of GI tract)
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6
Q

role of Olfactory ensheathing cells/glia (OECs)

A
  • ensheath non-myelinated axons of olfactory neurons
  • assist axonal regeneration.
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7
Q

describe the morphology of astrocytes

A

generally stellate (star-like)
- long branching processes
- contains GFAP (glial fibrillary acidic protein)
- provides structural support
- from surface under pia (glia limitans)
- astrocytes encase dendritic trees
- astrocyte end feet contact & enwrap BBB
- form a signalling (and transport) pathway between neurons & blood vessels

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8
Q

what is the most numerous and diverse types of neuroglia in the CNS?

A

astrocytes

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9
Q

describe the structural organisation of astrocyte-neuron networks

A
  • non-overlapping domains (volume)
  • each astrocyte occupies a distinct domain
  • single astrocyte contacts multiple dendrites of single neuron & single neurons associated with multiple astrocytes
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10
Q

describe the morphology of oligodendrocytes

A
  • fine processes (30-50 axons) from an oligodendrocyte end as flat sheets, which wind around axons to form myelin sheaths
  • along axon, consecutive myelin sheaths separate Nodes of Ranvier
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11
Q

describe the origin & role of NG2 (neurone-glia antigen-2 or chondroitin sulphate proteoglycan) expressing glia

A
  • derived from oligodendrocytes precursor cells, OPCs
  • form contacts incl. synapses with neurons
  • may persist as multipotent adult stem cells, activated by damage
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12
Q

describe the origin and role of microglia (the other type of glia in CNS)

A
  • mesodermal origin
  • inmmunocompetent in CNS/form brain immune system, activated by injury & disease
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13
Q

briefly describe the different way schwann cells exist in the PNS

A
  • glia cells of PNS
  • exist as myelinating & non-myelianting SCs
  • include perisynaptic SCs whoch ensheath terminal axon branches and synaptic boutons at the NMJ
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14
Q

describe the cell lineage of neural cells

A
  • derive from neural epihelial (forms neural tube)
  • multiple by symmetric division, then divide asymmetrically to form first neurons
  • neural epithelial cells in later stages of development transform into radial glia
  • radial glia undergo asymmetric division to form neurons or intermediate progenitor cells (IPCs)
  • IPCs can go onto form neurons, astrocytes or oligodendrocytes
  • at end of embryonic develeopment radial glia cells will transform into astrocytes
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15
Q

why can the neural epithelial cells be defined as true neural stem cells?

A
  • progeny of neural epithelial cells may differentiate into neurons or macroglia with equal probability
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16
Q

describe the cell lineage of Schwann cells

A
  • neuroepithelial cell (neural precursor) differentiate into schwann cell precursor
  • which differentiate into an immature schwann cell
  • depending on environment of immature Schwann cell (mostly axon diameter) it will differentiate into promyelinating SC and then myelinating SC or non-myelinating SC
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17
Q

schwann cell phenotype depends on contact with what?

A
  • if axons > 1 micrometre myelinating SC will result
  • if axons in vicinity of SC < 1 micrometre non-myelinating SC will result
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18
Q

1 schwann cell myelinates how many axons?

A
  • 1 SC myelinates 1 axon (in contrast to oligodendrocytes which myelinates 30-50)
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19
Q

what is radial sorting?

A
  • process by which SCs choose larger axons to myelinate during development
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20
Q

schwann cells have the ability to do what?

A
  • dedifferentiate if damaged & return to immature SC state
  • immature SC can look at axons in environment to redifferentiate into myelinating or non-myelinating SCs
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21
Q

describe the cell lineage of microglia

A

embryonic period:
- embryonic microglia cells arise from foetal macrophages (mesodermal origin)
2 week prenatal period:
- (embryonic microglia cells are also) microglia precursor cells (which) give rise to amoeboid microglia. these proliferate in coprus collusum then migrate into brain
adult brain:
- microglia evenly distributed throughout whole brain
- ramified (resting) until activated by damage or disease - then form **phagocytic **

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22
Q

describe the phylogeny of glia:neurons during evolution

A

increase in glia:neuron ratio
increase in size & complexity of astrocytes

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23
Q

what are the two types of synapses?

A
  • chemical
  • electrical
24
Q

electrical synapse formed because of what?

A
  • cell conection via ‘gap junctions’
  • connexion molecules bridging the gap
25
Q

what forms the tripartite synapse?

A
  • presynaptic terminal
  • post synaptic neuron
  • surrounding astrocytic processes
    (all contribute to activity of chemical synapse)
26
Q

what are the two types of transmission/signalling?

A
  • volume and wiring transmission
27
Q

what is wiring transmission?

A
  • targets designated synapses (electrical or chemical) and produces localised responses in perisynaptic astrocytic processes
28
Q

what is volume transmission?

A
  • diffusion & flow of signals in ECF of brain and in CSF along energy gradients (from source to target cells)
29
Q

what is intracellular vol transmission?

A
  • signal distributed through intracellular fluid
30
Q

give an example of volume neurotransmission

A
  • dopamine (DA) in the prefrontal cortex
  • there are few dopamine reuptake pumps in the prefrontal cortex, dopamine is available to diffuse to nearby receptor site
31
Q

what are the difference between wiring and volume transmission?

A

wiring: rapid, local, 1:1 signalling

volume: slow, diffuse, affecting populations of cells, sometimes at a distance

32
Q

what are some physiological properties of astrocytes?

A
  1. do not fire action potentials.
  2. have high K+ resting conductance and (very negative) resting membrane potential (-90mV).
  3. form a syncytium of cells connected by gap junctions.
  4. buffer/regulate extracellular K+ concentrations
33
Q

How is it possible for astrocytes to not be electrically excitable but still able to propagate a signal?

A
  • not electrically excitable because low density of VG channels in membrane
  • they’re able to propagate a signal (just not an action potential) by using calcium signalling
34
Q

describe how the astrocyte calcium wave mechanism works?

A
  • astrocytes form a continuous syncytium. A ‘wave’ of calcium can spread through a population of astrocytes, via gap junctions (A), or via extracellular signalling (B,C) e.g. via ATP release and ATP receptors
  • ## note: it is NOT calcium being pass on cell to cell

refer to lecture notes for (A),(B) and (C) references

35
Q

ATP released from astrocytes can be referred to as what?

A
  • gliotransmitters
  • others incl: glutamate, ATP and D-serine
36
Q

astrocytes are able to release what?

A

gliotransmitters

37
Q

which glia is responsible for: support ?

A

astrocytes

38
Q

what role do astrocytes play in homeostasis?

A
  • regulate K+ (K+ buffering)
  • water regulation
  • extracellular pH
39
Q

what is the role of astrocytes in maintenance of the BBB?

A
  • astrocytes contribute to the expression of:
    1. tight junction proteins and
    2. polarised expression of ion channels/transporters on capillary endothelial cells
40
Q

which glia cell is responsible for neurotransmitter uptake?

A

astrocytes

41
Q

which glia is responsible fpr transport and metabolism?

A

astrocytes

42
Q

which glia is responsible for the regulation of cerebral blood flow and respiration and how?

A
  • astrocytes sense neuronal firing via glutamate & regulate cerebral blood flow accordingly, using products of arachnoid acid (AA) metabolism
  • mechanisms detected for vasoconstriction (2-HETE) and vasodilation (prostaglandins)
43
Q

what is reactive astrogliosis?

A
  • a defensive brain reaction which is aimed at:
    (a) isolation of damaged area from rest of CNS tissue
    (b) reconstruction of BBB
    (c) facilitation of remodelling of brain circuits in areas surrounding the lesioned region
44
Q

which glia is responsible for myelination?

A

oligodendrocytes & schwann cells

45
Q

which glia is responisble for phagocytosis and immune functions?

A
  • microglia
46
Q

how do astrocytes buffer for K+ ?

A
  • high membrane permeability to K+ (K+ uptake) & gap junctions coupled syncytium allows astrocytes to redistribute K+ away from sites if neural activity, the K+ ‘spatial buffer’
47
Q

how do astrocytes allow for water regulation?

A
  • neuronal activity releases K+ & glutamate, and their entry into astrocytes causes water to follow osmotically
  • a high density of AQP4 water channels allows astrocytes to redistribute this water
48
Q

why is K+ buffering important?

A
  • [K+] in ECF is low and ECF vol is small so only need few K+ to enter ECF and make big change in [K+] in ECF as result of neuronal activity
  • Synaptic and axonal activity releases K+ plus CO2 and water
  • Astrocytes help buffer and redistribute these away from site of activity
49
Q

describe how astrocytes recycle glutamate?

A
  • use glutamate transporters to take up neuronally released glutamate (80% into astrocytes)
  • & convert it (glutamaine synthetase, GS) to glutamine for return to neuronal presynaptic terminal where it’s converted to glutamate or GABA (and packaged in vesicles - glutamate-glutamine shuttle
50
Q

role of astrocytes in neurotransmitters

A
  • uptake of NTs
  • terminates action of NT
  • recycles NT
  • protects against neurotoxicity
51
Q

what are the different components of the neurovascular unit?

A
  • cerebral capillary endothelial cells, basement membrane, astrocytes, oligodendrocytes, microglia, pericytes and neurons
52
Q

describe how the astrocyte-neuronal lactate shuttle works

A
  • glucose taken up by astrocyte transporters (GLUT-1) is converted to lactate (via glycolysis), passed to neurons as energy source via monocarboxylic acid transporters (MCT)
  • glutamate stimulates astrocyte GLUT-1 glucose transporter
  • this astrocyte-neuronal lactate shuttle may increase efficiency of neuronal energy supply
53
Q

Glial cells are essential for homeostasis of brain and supporting neurones through regulation of what?

A
  • Ions
  • Water
  • Neurotransmitters
  • Synaptic transmission
  • Blood-brain barrier
  • Blood flow
  • Response to injury
  • pH
54
Q

oligodendrocyte function?

A

make concentric lamellae of myelin which insulate axons

  • induce ion channel clustering at nodes of Ranvier - saltatory conduction
  • essential for axonal integrity
55
Q

what are the functions of the resting, activated and phagocytic function?

A

brain defence and immune system

3 distinct stages:

  • resting microglia-scanning brain territory supressed by presence of neurotransmitters
  • involved in surveillance

microglia activated by trauma

  • aim to destroy to foreign cells
  • aid neurones in overcoming damage e.g. secrete growth factors

phagocytic microglia

  • regain amoeboid shape
  • remove damaged cells and debris
56
Q

what are the functions of the resting, activated and phagocytic function?

A

brain defence and immune system

3 distinct stages:

  • resting microglia-scanning brain territory supressed by presence of neurotransmitters
  • involved in surveillance

microglia activated by trauma

  • aim to destroy to foreign cells
  • aid neurones in overcoming damage e.g. secrete growth factors

phagocytic microglia

  • regain amoeboid shape
  • remove damaged cells and debris

UNI Y2: Physiology & Pharmacology of the CNS (1 decks)

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