glial cells

Question 1

what are the 4 glial cells?

Answer 1

astrocytes
oligodendrocytes
microglia
ependymal

Question 2

where do astrocytes, oligodendrocytes and neurons orginate from?

Answer 2

neural stem cells in the ventricular and subventricular zones in the embryo

Question 3

where do microglia originate from?

Answer 3

peripheral macrophage-like cells which migrate into the CNS

Question 4

what is a common feature of all glial cells?

Answer 4

they are not electrically excitable, which means they cannot generate action potentials

Question 5

cajal and astrocytes

Answer 5

• noted existance of large/principal cells (neurons) and cells that connected to these principal cells and blood vessels
• these cells often showed a star shaped body so were named astrocytes

Question 6

types of astrocytes

Answer 6

1. protoplasmic
2. fibrous
3. radial (bergman glia)

Question 7

where are protoplasmic astrocytes found?

Answer 7

grey matter

Question 8

where are fibrous astrocytes found?

Answer 8

white matter of brain and spinal cord

Question 9

where are radial astrocytes found?

Answer 9

predominantly located in regions like the ventricular zone and the subventricular zone during brain development

Question 10

characteristics of astrocytes

Answer 10

1. small size of their cell body (typically <10micrometres)
2. numerous (often hundred) of thin (<1micrometres) hair-like processes which spread in all directions and infiltrate all spaces between neurons

Question 11

processes of astrocytes

Answer 11

• do not propagate APs and TF lack specialisation
• no axons or dendrites in astrocytes
• most located in grey matter spread their processes in all directions (protoplasmic) but there are also polarised aysmmetric astrocytes which have processes arranged in longitudinal bundles (bergman glia in the cerebellum)
• processes with end feet are often located on the surface of blood vessels where they for the key element of the BBB

Question 12

astrocytes insulate blood vessels from the parenchyma side and control BBB

Answer 12

the extensions of astrocytes, called astrocytic end-feet, wrap around blood vessels, especially in the capillaries (neurovascular unit)
astrocytic end-feet influence the function of the endothelial cells in the blood vessels, contributing to the formation and maintenance of tight junctions that control the passage of molecules

Question 13

barriers for diffusion of molecules via BBB:

Answer 13

1. endothelium (2 membranes)
2. basal lamina
3. astrocyte end-feet (2 membranes)

Question 14

what molecules can pass the BBB via diffusion?

Answer 14

only lipophilic molecules can pass BBB via diffusion
all other molecules need either carriers/transporters or specialised
channels

Question 15

how does water move across the BBB?

Answer 15

via aquaporins

Question 16

how does glucose move across the BBB?

Answer 16

assisstance of transporters from GLUT family

Question 17

how does lactic acid move across the BBB?

Answer 17

lactate moves using
monocarboxylate transporters (MCT)

Question 18

why do astrocytes no generate action potentials?

Answer 18

astrocytes do not generate action potentials but they have a very negative membrane potential
(usually below -80 mV) which can slowly change within a few millivolts
astrocytes cannot generate action potentials because they do not express any significant quantity of voltage gated
sodium channels

Question 19

why are astrocytes strongly polarised?

Answer 19

astrocytes have many very active potassium
channels (kir type)
this is the reason why they are so strongly polarised but also why their membrane has very low electrical resistance

Question 20

astrocytes and calcium excitability

Answer 20

since the membrane of astrocytes does not depolarise sufficiently, they cannot operate voltage-gated
calcium channels, which are the key mechanism for initiating fast vesicular exocytosis in neurones or endocrine cells.
astrocytes can, however, release Ca2+ from intracellular stores, particularly in response to stimulation of
G-protein-coupled receptors
the resulting Ca2+ increase can trigger vesicular exocytosis of transmitters

Question 21

what do astrocytes often form?

Answer 21

gap junctions
- ions (especially k
+ ions) and also larger molecules (e.g. glutamate, D-serine, lactate, glucose) can pass through
gap junctions
- they can therefore spread though the “astrocytic syncytium” and be widely distributed across
large areas (thousands of micrometers)
- this helps to keep the extracellular concentration of k
+ stable and also
to deliver molecules such as lactate and glucose to the network of neurones

Question 22

why is redistribution of potassium across wider areas important?

Answer 22

it helps prevent exessive local build up of potassium, depolarisation of neurons and generation of epileptic activity

Question 23

what do astrocytes release?

Answer 23

gliotransmitters

Question 24

examples of gliotransmitters

Answer 24

ATP
D-serine
glutamate
L-lactate
anandamide (endocannabinoid)

Question 25

how do astrocytes release gliotransmitters?

Answer 25

1. can be triggered by an increase in intracellular Ca2+, for example for release of ATP via exocytosis 2. can be gradient-dependent via diffusion through connexin hemichannels or transporter activity, for example for lactate

Question 26

ATP as a gliotransmitter

Answer 26

the main excitatory transmitters of astrocytes are purines, such as ATP (and adenosine which is formed from ATP in the extracellular space) ATP stimulates receptors on adjacent cells (neurones and glia) and raises intracellular Ca2+ this leads to “Ca2+ waves“ propagating through the astrocytic network

Question 27

astrocytes recycle neuronal glutamate

Answer 27

- astrocytes take up glutamate released in the synapses - in the astrocyte, glutamate is converted into glutamine which is then returned back to the neurones which can again re-convert it to glutamate, package it into vesicles and use it for synaptic transmission - this is known as glutamate-glutamine cycle that sustains glutamatergic neurotransmission

Question 28

key neuro-anatomical features of astrocytes

Answer 28

1. small soma and numerous processes but no dendrites or axons 2. end feet insulate the outer wall of all BB vessels, they control access to the brain for many essential molecules 3. connected by gap junctions and may form a synctium which ions and small molecules may be distributed between multiple cells

Question 29

essential physiological characteristics of astrocytes

Answer 29

1. astrocytes are not excitable (cannot generate action potentials) but usually have very negative membrane potentials 2. astrocytes display “calcium excitability” – fairly rapid elevations (seconds) of intracellular calcium 3. they release “glio-transmitters”, signalling molecules which affect neighbouring neurones and other astrocytes

Question 30

key functions of astrocytes in mammalian brains

Answer 30

1. they play an essential role in control of glutamate metabolism and removal from the synaptic cleft, this has a major effect on excitatory transmission in the brain 2. they control access of energy (glucose and lactate) to neurones; this has direct impact on the activity of neurones when the consumption of energy dramatically increases 3. astrocytes are not “passive” cells: they can actively participate in physiological processes by modulating adjacent neurones

Question 31

processes modulated by astrocytes

Answer 31

1. astrocytes on the ventral surface of the medulla are chemosensitive and participate in responses to blood CO2 2. astrocytes are highly mechano-sensitive, the slightest mechanical disturbance of their membrane causes powerful release of ATP. they may be participating in regulation of cerebral blood flow. 3. astrocytes in the hippocampus affect neuronal circuits involved in memory formation, this could be via supply of energy (lactate) on demand