DGN - Astrocytes and BBB

Question 1

What are the functions of astrocytes? (6)

Answer 1

1. Neurogenesis and gliogenesis in the adult brain
2. Neuronal guidance in development: role of radial glia
3. Regulation of synaptogenesis and synaptic maturation in development
4. Structural function: microarchitecture of the brain. Astrocytes define and connect domains that include neurons, synapses and blood vessels. Communication through gap junctions
5. Creation of the blood-brain barrier
6. Synaptic modulation

Question 2

What is the role of astrocytes in the tripartite synapse?

Answer 2

Pre-synaptic and post-synaptic synapses are surrounded and insulated by astrocytes

• ~60% of axon-dendritic synapses are surrounded by astroglial membranes (hippocampus)
• 80% of large perforated synapses (the most frequent type) are enwrapped by astrocytes

Question 3

What are 3 pieces of evidence for the tripartite synapse?

Answer 3

Astrocytes are excitable cells: in response to presynaptic or postsynaptic stimulation, astrocytes are capable of producing transient changes in their intracellular calcium concentrations through release of calcium stores from the ER

Astrocytes communicate bidirectionally with neurons: able to detect neurotransmitters and other signals released from neurons at the synapse and can release their own neurotransmitters or gliotransmitters that are, in turn, capable of modifying the electrophysiological excitability of neurons

Astrocytes are capable of responding selectively to stimuli

Question 4

How do astrocytes participate in glutamatergic signaling? (3)

Answer 4

• Astrocytes participate in Glu clearance and provision of Gln as substrate
• Glu main target receptors include Kainate receptors, metabotropic glutamate receptors (mGluRs), and especially NMDA receptors
• Other functions of this gliotransmitter include synchronous depolarization, increasing the frequency of postsynaptic currents, and also increasing the likelihood of release and frequency of AMPA-receptor-dependent postsynaptic currents

Question 5

What are gliotransmitters, and what role do they play in astrocyte-neuron communication?

Answer 5

Molecules produced by glial cells which can signal to neurons

• ATP targets P2X receptors, P2Y, and A1 receptors
• ATP has several functions including insertion of AMPA receptors into the postsynaptic terminal, paracrine activity through calcium waves in astrocytes, and suppression of synaptic transmission

Question 6

How do astrocytes respond selectively to stimuli in the hippocampal stratum oriens?

Answer 6

Astrocytes in the hippocampal stratum oriens respond selectively to synaptic activity from glutamatergic and cholinergic neurons by producing changes in their intracellular calcium concentrations

• These responses drive astrocyte-dependent long-term potentiation (LTP) and help control levels of glutamate in the synaptic cleft

Question 7

What is another function of astrocytes?

Answer 7

Astrocytes integrate and modulate information from their synaptic inputs

Question 8

What is the blood-brain barrier, and how is it formed? (3)

Answer 8

• Barrier between the intracerebral blood vessels and the brain parenchyma (functional space where neurones reside)
• Formed by tight junctions between endothelial cells and astroglial endfeet
• Present throughout the brain except for circumventricular organs (CVOs), neurohypophysis, pineal gland, subfornical organ and lamina terminalis, involved in neuroendocrine signalling

Question 9

Where must solutes pass through?

Answer 9

Every solute that crosses the BBB MUST pass through endothelial cells:

• Selective permeability to essential nutrients to enter and to metabolites to leave

Question 10

What are the specific transporters at the endothelial cells involved in the blood-brain barrier? (4)

Answer 10

• Energy-dependent ABC transporters: excrete xenobiotics (impermeability to drugs, antibiotics, etc)
• Amino acid transporters
• GLUT1 glucose transporters
• Ion exchangers

Question 11

What are the specific transporters at the astrocyte endfeet involved in the blood-brain barrier? (3)

Answer 11

• Glucose transporters: uptake and distribution to neurons
• K+ channels (Kir4.1)
• Water channels (aquaporin-4)

Question 12

How does axon injury lead to the formation of a glial scar?

Answer 12

Spinal cord injury → Activated microglia → Form a glial scar

• Limits the access
• Prevent damage to other areas

Question 13

How does inflammation lead to the formation of a glial scar?

Answer 13

Invasion of lymphocytes and macrophages result in activation of microglia

• Build up of astrocytes form a glial scar

If the scar is left untreated, it may become a permanent scar