Glial Cell Biology ILO 6 - Outline main factors and signalling pathway that control activation of brain glial cells Flashcards
What ion channels are present on astrocytes that are common to neurons?
K+ and Na+
True or False - astrocytes can propagate action potentials
False
True or False - astrocytes can propagate calcium waves
True
What is an activated astrocyte called?
Reactive astrocyte - reacts to changes in environment
What process leads to a Ca2+ spike in astrocytes?
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
How can Ca2+ waves be stimulates in vitro?
Can mechanically stimulate astrocytes and increase Ca2+ signal
What are the sources of Ca2+ in astrocytes and what are some of the transporters involved?
Endoplasmic reticulum
Mitochondria
Can be imported from the extracellular space by voltage gated Ca2+ channels and Na+ exchanger
What signalling pathway can induce Ca2+ release in astrocytes?
Gaq signalling
IP3 acting on IP3R on ER membrane releases ER calcium stores
What does increased Ca2+ in astrocytes cause?
Release of gliotransmitters - ATP, D-serine, glutamate
Where are Ca2+ spikes witnessed in microglia?
Processes and not the soma
Most Ca2+ signal seen in extending branches
How does microglia Ca2+ activity relate to neuronal activity?
As neuronal activity decreases, microglia activity increases
How does microglia Ca2+ levels change in the presence of kainate?
Kainate is an excitatory agonist
Microglia Ca2+ increases in presence of kainate
How do microglia activation/Ca2+ levels compare in normal waking, sedation and seizure states?
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
Name 3 receptors that are present on the microglia surface and raise intracellular Ca2+ through the IP3 pathway
P2YR mGluR mAChR HR NK-1R ET-R
Name 2 receptors present on the microglia surface that are Ca2+ ion channels
p2XR
iGluR
What are the 5 isoforms of GFAP and where are they expressed?
alpha, beta, gamma, lambda, kappa
Expressed heterogeneously across the brain in physiology and pathophysiology
Distribution/role not fully understood but required for active astrogliosis
What is reactive astrogliosis?
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
Name some of the triggers of astrogliosis.
Cell damage/death Ischemia Neuronal hyperactivity Infection Neurodegeneration Metabolic disorders
What is the function of reactive astrogliosis?
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
What defines A1 and A2 activated astrocytes in reactive astrogliosis?
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.
What defines M1 and M2 activated microglia?
M1 - proinflammatory and considered harmful
M2 - considered helpful in recovery
What are the 4 properties of microglia activation signals?
Not usually seen or seen at much lower concentrations
Presented in a specific state
Exist in an abnormal form
