L6 - Glia and Multiple Sclerosis Flashcards

1
Q

What proportion of brain is neurons

A

10%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What other cells make up the brain?

A
Glia
blood vessel
astrocytes
oligodendrocytes
microglia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

When do glial cells first come about?

A

Last, after the neurogenesis of neurons

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What do astrocytes do?

A

Takes glucose from capillary and gives it to neuron

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What do astrocytes do at the synaptic cleft?

A

Takes up glutamate using proton motive force and then gives it back to presynapse

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Why does glycolysis have to occur in astrocytes?

A

Used for Na ATPase and proton motive force

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What happens to the glucose that goes through the astrocyte destined for the neurons and why?

A

Glycolysis makes lactate

Neurons cannot use glucose very well

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

How is the glutamate transferred back into the neuron?

A

Using ATP to turn it into glutamine then goes in

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What does high Ca in astrocytes do?

A

Leads to glutamate release

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What happens to astrocytes during a stroke?

A

Release large amounts of glutamate from lysosomes and into cleft
Activate neurons and get cytotoxix stress

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What do oligocendrocytes do?

A

Wrap up axons in myelin sheath

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the components of the myelin sheath?

A

Proteolipid proteins

Myelin basic protein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

How do oligodentrocytes migrate?

A

PDGF promotes motility
Signals are chemorepellent eg netrin tell them to go
Stop signals in ECM

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

WHere do microglia arise from?

A

macrophages outside the CNS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are are the features of microglia?

A

Tidy up any damage
Phagocytic
Antigen presenting cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is gliosis?

A

Astrocytes and microglia forming scar tissue

17
Q

How are microglia led to the place of damage?

18
Q

Why is HIV such a bad disease?

A

infects microglia

19
Q

What are the features of MS?

A

Demylenating disease of the CNS
Symptoms - weak movement, blurred vision (optic nerve), fatigue
IgG levels high

20
Q

What does a scan of aNn MS patient show?

A

Lesions where white matter has been destroyed

21
Q

Why is the risk of MS higher in US, UK, Central Europe, NZ than in equatorial regions?

A

Hypothesis on sunlight exposure or day length

22
Q

What kind of genes are generally mutated in MS?

A

T cell related genes

23
Q

What are the environment factors that may be important in MS?

A

Possibly associated with virus’

Sunlight, solvents, pollution, temp

24
Q

What is the t cell model for MS?

A

T cell invasion and inflammation

Gobble up oligodendrocytes

25
How could oxidative stress possibly cause MS?
Influx of Na ions, so mitochondria must produce a lot of ATP, and so produce oxidative stress Cells degenerate, let in more Ca, cascades to more damage
26
How can cannabis be used for MS?
Relieves muscle stiffness, body pain, muscle spasms
27
What drugs could help with MS?
B-interferon-1B Glatiramer acetate Natalizumab
28
How is B-interferon-1B involved in MS?
Levels go up before relapse | Inhibits gamma-interferon
29
What is the success of B-interferon?
Reduces relapses from 69% of patients in 2 years to 55%
30
How does glatiramer acetate help MS?
Molecular mimic of a region of myelin basic protein so HLA binds to that
31
Whats the problem with MS drugs?
Very expensive | Not very effective
32
What were the problems with natalizumab?
Had inflammation of white matter in some patients because of John Cunningham virus
33
What are some recent drugs for MS?
Oral - fingolimod - blocks lymphocyte migration by internalising receptor Dimethyl fumarate - counters oxidative stress in Nrf2 pathway
34
What is Alemtuzumab?
Drug that affects migration of lymphocytes Monoclonal antibody Anti CD52 a surface glycoprotein Reduces TNF-a, IL-6
35
Whats stopping oligodendrocytes repairing the myelination?
Blocked by glial scarring
36
What do we think affects remyelination?
Macrophages not clearing myelin debris which contains inhibitors of differentiation such as wnt signals