Lecture 2: Intro to Glia Cells Flashcards
1
Q
what are the two major classes of cells in the brain?
A
- neurons
- glia
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)
3
Q
state one feature all neuroglia share?
A
all the homeostatic cells of the NS (PNS & CNS)
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
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)
6
Q
role of Olfactory ensheathing cells/glia (OECs)
A
- ensheath non-myelinated axons of olfactory neurons
- assist axonal regeneration.
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
8
Q
what is the most numerous and diverse types of neuroglia in the CNS?
A
astrocytes
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
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
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
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
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
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
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
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
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
18
Q
1 schwann cell myelinates how many axons?
A
- 1 SC myelinates 1 axon (in contrast to oligodendrocytes which myelinates 30-50)
19
Q
what is radial sorting?
A
- process by which SCs choose larger axons to myelinate during development
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
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 **
22
Q
describe the phylogeny of glia:neurons during evolution
A
increase in glia:neuron ratio
increase in size & complexity of astrocytes
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
what forms the tripartite synapse?
- presynaptic terminal
- post synaptic neuron
- surrounding astrocytic processes
(all contribute to activity of chemical synapse)
26
what are the two types of transmission/signalling?
- volume and wiring transmission
27
what is wiring transmission?
- targets designated synapses (electrical or chemical) and produces localised responses in perisynaptic astrocytic processes
28
what is volume transmission?
- diffusion & flow of signals in ECF of brain and in CSF along energy gradients (from source to target cells)
29
what is intracellular vol transmission?
- signal distributed through intracellular fluid
30
give an example of volume neurotransmission
- **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
what are the difference between wiring and volume transmission?
wiring: rapid, local, 1:1 signalling
volume: slow, diffuse, affecting populations of cells, sometimes at a distance
32
what are some physiological properties of astrocytes?
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
How is it possible for astrocytes to not be electrically excitable but still able to propagate a signal?
- 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
describe how the astrocyte calcium wave mechanism works?
- 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
ATP released from astrocytes can be referred to as what?
- gliotransmitters
- others incl: glutamate, ATP and D-serine
36
astrocytes are able to release what?
gliotransmitters
37
which glia is responsible for: support ?
astrocytes
38
what role do astrocytes play in homeostasis?
- regulate K+ (K+ buffering)
- water regulation
- extracellular pH
39
what is the role of astrocytes in maintenance of the BBB?
- astrocytes contribute to the expression of:
1. tight junction proteins and
2. polarised expression of ion channels/transporters on capillary endothelial cells
40
which glia cell is responsible for neurotransmitter uptake?
astrocytes
41
which glia is responsible fpr transport and metabolism?
astrocytes
42
which glia is responsible for the regulation of cerebral blood flow and respiration and how?
- 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
what is reactive astrogliosis?
- 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
which glia is responsible for myelination?
oligodendrocytes & schwann cells
45
which glia is responisble for phagocytosis and immune functions?
- microglia
46
how do astrocytes buffer for K+ ?
- 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
how do astrocytes allow for water regulation?
- 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
why is K+ buffering important?
- [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
describe how astrocytes recycle glutamate?
- 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
role of astrocytes in neurotransmitters
- uptake of NTs
- terminates action of NT
- recycles NT
- protects against neurotoxicity
51
what are the different components of the neurovascular unit?
- cerebral capillary endothelial cells, basement membrane, astrocytes, oligodendrocytes, microglia, pericytes and neurons
52
describe how the astrocyte-neuronal lactate shuttle works
- 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
Glial cells are essential for homeostasis of brain and supporting neurones through regulation of what?
- Ions
- Water
- Neurotransmitters
- Synaptic transmission
- Blood-brain barrier
- Blood flow
- Response to injury
- pH
54
oligodendrocyte function?
make concentric lamellae of myelin which insulate axons
- induce ion channel clustering at nodes of Ranvier - saltatory conduction
- essential for axonal integrity
55
what are the functions of the resting, activated and phagocytic function?
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
what are the functions of the resting, activated and phagocytic function?
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
