Lecture 15-The Role of Glial Cells in the Brain 3

Question 1

Why do astrocytes have their name?

Answer 1

Cause they look like stars: have long branched processes coming of a center

Question 2

Where are astrocytes most present? (what type of matter?)

Answer 2

In grey matter as associate with cell bodies and support synapses

Question 3

What did researchers find when looking at albert Einstein’s brain and what does this indicate about astrocytes?

Answer 3

• He didn’t have more neurons like researchers thought originally
• He had more astrocytes
• This shows the importance of astrocytes for communication within neural networks

Question 4

What are three functions of astrocytes?

Answer 4

1. Modulation of communication (at synapses)
2. Nutrient transport from the blood to neurons (cerebral blood flow)
3. Supporting myelination coverage of neurons

Ultimately astrocytes are highly invovled in the physical structuring of the brain

Question 5

What aspects of astrocyte morphology are critical to their functioning?

Answer 5

• Size
• Structure
• Length of processes
• End feet

Question 6

How can an astrocyte be distinguished from other cells/ glia?

Answer 6

-Well developed cytoskeleton:
• dominated by intermediate filaments (glial fibrillary acidic protein
(GFAP) or S100 = calcium binding protein ß (S100ß)
• also microtubules and actin/mitochondria
• Many gap junctions

Distal endfeet
• Dilated on blood vessels (make large area of contact so that can exchange as much material as possible- glucose)

Astrocytes kind of just squish into any available space

Question 7

What are the two types of astrocytes and where are they respectively found?

Answer 7

Fibrous – (white matter):
Radial glia - radially arranged in white matter and more specialized forms

Protoplasmic – (grey matter):
Majority of astrocytes. Envelop synapses

Question 8

What is meant by the phrase: Astrocytes have exclusive territories?

Answer 8

• Each astrocyte covers a specific territory that interfaces with the microvasculature and that might include thousands of synapses
• Discrete region of interaction of the fine terminal processes (yellow)

Question 9

True or false: astrocytes have unordered arrangements with lots of overlap?

Answer 9

False: astrocytes actually have ordered arrangements with minimal overlap

Question 10

What type of junctions are common between astrocytes? What does this mean?

Answer 10

• Gap junctions (semi- permeant feature between two cells, pass ions through to communicate, not as tight as tight junction but still close together)
• Free communication between astrocytes

Question 11

How do astrocytes communicate/ pass on information?

Answer 11

• Communicate via Ca2+ waves: Ca2+ binding protein – store and release Ca2+
• Glutamate causes Calcium wave

Question 12

Are astrocytes static or dynamic? What is the reason for this?

Answer 12

• Dynamic: Astrocytic processes show spontaneous morphological changes in a matter of minutes
• Reason: Astrocytes have to adapt to what the synapses are doing (synapses/ dendritic spines constantly changing)

Question 13

What is shown when end feet of astrocyte are destroyed by a lazer?

Answer 13

They regrow in order to continue contact with blood vessels

Question 14

What are astrocytes intimately associated with? How can this be shown?

Answer 14

• Neurons

- Shown through fluorescent images where neurons exist in green and astrocytes are red

Question 15

What does the tripartite synapse consist of?

Answer 15

• Presynaptic
• Postsynaptic
• Astrocyte: has bidirectional contribution i.e. to the axon or the dendrite

Question 16

What does the astrocyte do at the tripartite synapse?

Answer 16

• Takes up potassium from the axon via channels
• Buffers calcium
• Take’s up the neurotransmitter glutamate from the synaptic clef pumps Gln back into the axon

Question 17

How is glutamate essential in Glutamate uptake & recycling at the synapse?

Answer 17

-Neurons depend on astrocytes for glutamine

-Used to synthesise:
Glutamate
GABA
Aspartate

-Basically not all glutamate released in the syntactic clef immediately goes to post synaptic membrane instead 80% is taken up by the astrocyte and turns glutamine which then turns into the above

Question 18

How do astrocytes maintain ionic homeostasis?

Answer 18

• K+ buffer
• Have the proteins that the neighbouring neuron has

-Voltage gated channels and Neurotransmitter receptors

Question 19

What is the evidence that astrocytes not only listen to the synapses but talk to them?

Answer 19

• Synaptic-like micro-vesicles (SLMVs)
• Release gliotransmitters via exocytosis
• Ca2+ release from endoplasmic reticulum
• Have ion channels and receptors in membrane

Allows astrocytes to act on neurons, vessels, and other glia

Question 20

What are gliotransmitters?

Answer 20

They are astrocyte signaling molecules i.e. glutamate, serotonin, ATP, adenosine

IP3 cause release of calcium from internal stores. From ER get calcium traveling out

Question 21

How do astrocytes modulate neuronal activity?

Answer 21

Glutamate release presynaptically
activates ionotropic glutamate receptors -1 (AMPA, MNDA)
activates metabotropic receptors – astrocyte -2

Glutamate release from astrocyte to post-synaptic neuron
activates extrasynaptic NR2B-containing NMDA receptors
to trigger slow inward currents (SICs) – 3
Changes membrane potential

Question 22

What do the GAP junctions between astrocytes mean in terms of how far a signal propogates?

Answer 22

• Activity at one synapse can influence distant synapses via astrocytes
• Signals propagated through GAP junctions Ins(1,4,5)P3 and Extracellular ATP

Question 23

What is a proposed mechanism for the synchronization of neurons involving astrocytes?

Answer 23

-Synchronization of neurons by astrocytic glutamate release

• Astrocyte (green) contacts a number of neurons across 100µm (training the neurons together)
• Results in neuronal synchronization of these neurons
• Known as a neuronal domain

Question 24

How do astrocytes get energy?

Answer 24

By controlling blood flow. Cerebral blood flow provides nutritional support from the blood to a neuron. Astrocytes are the mediator of this by having end processes that make contact with the endothelial cells/ blood vessels. Gap junctions between the astrocytes and between the end feet at the blood vessels allow help in the transport of nutrients.

Question 25

How does the vascular system know that neurons in active parts of the brain need more energy (more glucose)?

Answer 25

Astrocytes= they are the only connection between the vasculature and neurons

Question 26

How does neuronal activity lead to vasodilation and increased blood flow?

Answer 26

• Coordinated by astrocytes

- Glutamate receptors, Ca2+ transient travels to end feet, release of vasodilators

Question 27

How are astrocytes dysfunctional in Alzheimer’s disease?

Answer 27

1. Reactive astrocytes become Aβ producers.
2. Aβ increases Ca2+ signaling in astrocytes.
3. Aβ inhibits astrocyte glutamate uptake
4. Glutamate excitotoxicity increases Ca2+ signaling in neurons, leading to inhibition of LTP and memory loss
5. Impaired astrocytic glucose and reduced lactate release
6. Increased spontaneous Ca2+ signaling induces abnormal vascular responses in blood vessels