Astrocytes

Question 1

CNS Development and synapse formation

Answer 1

• interaction between astrocytes and developing neurons play important role in dendritic growth, effective synaptic formation, and removal of unwanted synapses
• secrete growth-promoting and growth-inhibiting molecules important for axon guidance and glial boundaries
• help in the pruning and clearance of unwanted axons and synapses
• stabilize newly formed synapses

Question 2

Synaptic Homeostasis - regulating axonal conduction and synaptic activity (also Potassium and GLU specific)

Answer 2

• astrocytes have have processes which enclose synapses
• K+ and H+ are also taken up by astrocytes and are dissolved
• GABA is removed from synaptic cleft and is partially recycled
• Because of extensive gap junctions between astrocytes and to other cells, they can deposit material at distant sites via end feed connections that surround blood capillaries.

Potassium clearing

• when neurons fire, they release K+ into the synapse
• K+ is taken up by astrocytes, which transport it to and release at distant contacts with blood cells

—> important because excess extracellular K+ interferes with signalling (changes the potential)

—> taking up K+ means that they can maintain the efficiency of neuronal signalling

—> if K+ accumulates in synaptic cleft, this can lead to seizures

—> if K+ or other ions accumulate together with water, brain swelling can occur

GLU clearing

• allows astrocytes to maintain homeostasis at the synapse by removing excess GLU
• GLU is recycled into glutamine (to keep concentration of astrocytic concentration of GLU low) and then transferred back to neuron
• if astrocytes wouldn’t clear GLU, it would accumulate in cleft and lead to cell death via excitotoxicity

Question 3

Astrocytes are part of the synapse

Answer 3

• visualization of astrocytes in acute brain slices has shown that astrocytes do far more than just maintain homeostasis at the synapse
  —> they are active players in neuronal and glial signalling, playing important roles in learning, memory, and synaptic plasticity
• from synapses together with the pre and post synaptic neurons

—> modulate synaptic transmission by release of neurotransmitters and help determine the excitatory signaling in the CNS

• GLU released by astrocytes can increase the frequency of both inhibitory and excitatory postsynaptic currents
• patch clamping studies have shown:

–> GLU released from astrocytes acts on presynaptic neurons and on blood vessels

–> GLU released from astrocytes in response to increased intracellular Ca2+ acts on NMDA receptors which mediate slow inward currents in postsynaptic neurons

• Astrocytes release ATP in response to synaptic activity which inhibits GLU release from neighbouring presynaptic neurons and therefore inhibits excitatory synaptic transmission

Question 4

Astrocytes have NT receptors

Answer 4

• e.g. Bergmann glia in cerebellum have GLU receptors
• leads to an increase in Ca2+ in glia-
• leads to cascade of Ca2+ increase amongst neighboring astrocytes
• able to modulate neuronal activity- release nutrients and regulate blood flow

Question 5

Astrocytes are involved in the BBB and control blood flow

Answer 5

• endothelial cells which form part of the BBB are surrounded by astrocyte end feet
• specific sub-types of astrocytes interact with blood vessels
• Astrocytes are though to regulate the specialized roles of endothelial cells including the tight junction formation, localisation of transporters, and production of specialised anti-oxidant enzymes
• secrete various angiogenic factors that are thought to play a role in development of the new brain capillary function
• astrocytic end feet consist of proteins that are involved in ion, glucose, and water homeostasis
• In vivo studies have shown that GLU released by neurons acts of receptors on astrocytes, leading to an increase in Ca2+ leading to vasodilation of capillaries

—> may be capable of coupling synaptic activity to local blood flow and BBB permeability

Question 6

Astrocytes precent energy depletion and protect neurons

Answer 6

• astrocytes protect neurons from energy depletion when glucose expenditure exceeds availability be releasing lactate
• have higher concentrations of anti-oxidants than neurons so can protect them from oxidative damage
• form glial scar around damaged cells to prevent injury from spreading