Glial Cell Biology ILO 6 - Outline main factors and signalling pathway that control activation of brain glial cells

Question 1

What ion channels are present on astrocytes that are common to neurons?

Answer 1

K+ and Na+

Question 2

True or False - astrocytes can propagate action potentials

Answer 2

False

Question 3

True or False - astrocytes can propagate calcium waves

Answer 3

True

Question 4

What is an activated astrocyte called?

Answer 4

Reactive astrocyte - reacts to changes in environment

Question 5

What process leads to a Ca2+ spike in astrocytes?

Answer 5

Ca2+ in neurons leads to action potential firing and swelling of axons -> activation of stretch activated channels -> release of ATP -> ATP acts of purinergic receptors on astrocytes -> Ca2+ stores released

Question 6

How can Ca2+ waves be stimulates in vitro?

Answer 6

Can mechanically stimulate astrocytes and increase Ca2+ signal

Question 7

What are the sources of Ca2+ in astrocytes and what are some of the transporters involved?

Answer 7

Endoplasmic reticulum
Mitochondria
Can be imported from the extracellular space by voltage gated Ca2+ channels and Na+ exchanger

Question 8

What signalling pathway can induce Ca2+ release in astrocytes?

Answer 8

Gaq signalling

IP3 acting on IP3R on ER membrane releases ER calcium stores

Question 9

What does increased Ca2+ in astrocytes cause?

Answer 9

Release of gliotransmitters - ATP, D-serine, glutamate

Question 10

Where are Ca2+ spikes witnessed in microglia?

Answer 10

Processes and not the soma

Most Ca2+ signal seen in extending branches

Question 11

How does microglia Ca2+ activity relate to neuronal activity?

Answer 11

As neuronal activity decreases, microglia activity increases

Question 12

How does microglia Ca2+ levels change in the presence of kainate?

Answer 12

Kainate is an excitatory agonist

Microglia Ca2+ increases in presence of kainate

Question 13

How do microglia activation/Ca2+ levels compare in normal waking, sedation and seizure states?

Answer 13

Waking - microgila Ca2+ very low
Sedation - increased activation and Ca2+ in branches
Seizure - similar activation of microglia as sedation but more present in the soma

Question 14

Name 3 receptors that are present on the microglia surface and raise intracellular Ca2+ through the IP3 pathway

Answer 14

P2YR
mGluR
mAChR
HR
NK-1R
ET-R

Question 15

Name 2 receptors present on the microglia surface that are Ca2+ ion channels

Answer 15

p2XR

iGluR

Question 16

What are the 5 isoforms of GFAP and where are they expressed?

Answer 16

alpha, beta, gamma, lambda, kappa
Expressed heterogeneously across the brain in physiology and pathophysiology
Distribution/role not fully understood but required for active astrogliosis

Question 17

What is reactive astrogliosis?

Answer 17

A spectrum of molecular, cellular and functional changes in astrocytes as a response to various brain diseases and injury
Degree of astrogliosis depends on severity of stimuli
Regulated by a variety of intra- and intercelular molecules
Can be beneficial and detrimental

Question 18

Name some of the triggers of astrogliosis.

Answer 18

Cell damage/death
Ischemia
Neuronal hyperactivity
Infection
Neurodegeneration
Metabolic disorders

Question 19

What is the function of reactive astrogliosis?

Answer 19

Protection against glutamate and ammonium toxicity, and oxidative stress
Degradation of a-beta peptides
Facilitation of BBB repair
Reduction of vascular oedema after trauma, stoke or obstructive hydrocephalus
Regulation of extracellular fluid and ion balance
Limitation of inflammatory cells or infectious agent spread

Question 20

What defines A1 and A2 activated astrocytes in reactive astrogliosis?

Answer 20

A1 - express complement cascade genes(C3), destructive to synapses and considered harmful. Induced by inflammation (IL-1a, TNFa, C1q)
A2 - express neurotrophic factors, considered protective, increase S100a10 and STAT3. Unsure what induces phenotype.

Question 21

What defines M1 and M2 activated microglia?

Answer 21

M1 - proinflammatory and considered harmful

M2 - considered helpful in recovery

Question 22

What are the 4 properties of microglia activation signals?

Answer 22

Not usually seen or seen at much lower concentrations
Presented in a specific state
Exist in an abnormal form