Lecture 15-The Role of Glial Cells in the Brain 3 Flashcards
Why do astrocytes have their name?
Cause they look like stars: have long branched processes coming of a center
Where are astrocytes most present? (what type of matter?)
In grey matter as associate with cell bodies and support synapses
What did researchers find when looking at albert Einstein’s brain and what does this indicate about astrocytes?
- 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
What are three functions of astrocytes?
- Modulation of communication (at synapses)
- Nutrient transport from the blood to neurons (cerebral blood flow)
- Supporting myelination coverage of neurons
Ultimately astrocytes are highly invovled in the physical structuring of the brain
What aspects of astrocyte morphology are critical to their functioning?
- Size
- Structure
- Length of processes
- End feet
How can an astrocyte be distinguished from other cells/ glia?
-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
What are the two types of astrocytes and where are they respectively found?
Fibrous – (white matter):
Radial glia - radially arranged in white matter and more specialized forms
Protoplasmic – (grey matter):
Majority of astrocytes. Envelop synapses
What is meant by the phrase: Astrocytes have exclusive territories?
- 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)
True or false: astrocytes have unordered arrangements with lots of overlap?
False: astrocytes actually have ordered arrangements with minimal overlap
What type of junctions are common between astrocytes? What does this mean?
- 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
How do astrocytes communicate/ pass on information?
- Communicate via Ca2+ waves: Ca2+ binding protein – store and release Ca2+
- Glutamate causes Calcium wave
Are astrocytes static or dynamic? What is the reason for this?
- 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)
What is shown when end feet of astrocyte are destroyed by a lazer?
They regrow in order to continue contact with blood vessels
What are astrocytes intimately associated with? How can this be shown?
- Neurons
- Shown through fluorescent images where neurons exist in green and astrocytes are red
What does the tripartite synapse consist of?
- Presynaptic
- Postsynaptic
- Astrocyte: has bidirectional contribution i.e. to the axon or the dendrite
What does the astrocyte do at the tripartite synapse?
- 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
How is glutamate essential in Glutamate uptake & recycling at the synapse?
-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
How do astrocytes maintain ionic homeostasis?
- K+ buffer
- Have the proteins that the neighbouring neuron has
-Voltage gated channels and Neurotransmitter receptors
What is the evidence that astrocytes not only listen to the synapses but talk to them?
- 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
What are gliotransmitters?
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
How do astrocytes modulate neuronal activity?
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
What do the GAP junctions between astrocytes mean in terms of how far a signal propogates?
- Activity at one synapse can influence distant synapses via astrocytes
- Signals propagated through GAP junctions Ins(1,4,5)P3 and Extracellular ATP
What is a proposed mechanism for the synchronization of neurons involving astrocytes?
-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
How do astrocytes get energy?
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.
How does the vascular system know that neurons in active parts of the brain need more energy (more glucose)?
Astrocytes= they are the only connection between the vasculature and neurons
How does neuronal activity lead to vasodilation and increased blood flow?
- Coordinated by astrocytes
- Glutamate receptors, Ca2+ transient travels to end feet, release of vasodilators
How are astrocytes dysfunctional in Alzheimer’s disease?
- Reactive astrocytes become Aβ producers.
- Aβ increases Ca2+ signaling in astrocytes.
- Aβ inhibits astrocyte glutamate uptake
- Glutamate excitotoxicity increases Ca2+ signaling in neurons, leading to inhibition of LTP and memory loss
- Impaired astrocytic glucose and reduced lactate release
- Increased spontaneous Ca2+ signaling induces abnormal vascular responses in blood vessels
