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Brain in Health & Disease > L6 - Glia and Multiple Sclerosis > Flashcards

L6 - Glia and Multiple Sclerosis Flashcards

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The Brain flashcards
1
Q

What proportion of brain is neurons

A

10%

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2
Q

What other cells make up the brain?

A 
Glia
blood vessel
astrocytes
oligodendrocytes
microglia
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3
Q

When do glial cells first come about?

A

Last, after the neurogenesis of neurons

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4
Q

What do astrocytes do?

A

Takes glucose from capillary and gives it to neuron

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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

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6
Q

Why does glycolysis have to occur in astrocytes?

A

Used for Na ATPase and proton motive force

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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

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8
Q

How is the glutamate transferred back into the neuron?

A

Using ATP to turn it into glutamine then goes in

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9
Q

What does high Ca in astrocytes do?

A

Leads to glutamate release

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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

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11
Q

What do oligocendrocytes do?

A

Wrap up axons in myelin sheath

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12
Q

What are the components of the myelin sheath?

A

Proteolipid proteins

Myelin basic protein

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13
Q

How do oligodentrocytes migrate?

A

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

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14
Q

WHere do microglia arise from?

A

macrophages outside the CNS

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15
Q

What are are the features of microglia?

A

Tidy up any damage
Phagocytic
Antigen presenting cells

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16
Q

What is gliosis?

A

Astrocytes and microglia forming scar tissue

17
Q

How are microglia led to the place of damage?

A

TNFa

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
Q

How could oxidative stress possibly cause MS?

A

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
Q

How can cannabis be used for MS?

A

Relieves muscle stiffness, body pain, muscle spasms

27
Q

What drugs could help with MS?

A

B-interferon-1B
Glatiramer acetate
Natalizumab

28
Q

How is B-interferon-1B involved in MS?

A

Levels go up before relapse

Inhibits gamma-interferon

29
Q

What is the success of B-interferon?

A

Reduces relapses from 69% of patients in 2 years to 55%

30
Q

How does glatiramer acetate help MS?

A

Molecular mimic of a region of myelin basic protein so HLA binds to that

31
Q

Whats the problem with MS drugs?

A

Very expensive

Not very effective

32
Q

What were the problems with natalizumab?

A

Had inflammation of white matter in some patients because of John Cunningham virus

33
Q

What are some recent drugs for MS?

A

Oral - fingolimod - blocks lymphocyte migration by internalising receptor
Dimethyl fumarate - counters oxidative stress in Nrf2 pathway

34
Q

What is Alemtuzumab?

A

Drug that affects migration of lymphocytes
Monoclonal antibody
Anti CD52 a surface glycoprotein
Reduces TNF-a, IL-6

35
Q

Whats stopping oligodendrocytes repairing the myelination?

A

Blocked by glial scarring

36
Q

What do we think affects remyelination?

A

Macrophages not clearing myelin debris which contains inhibitors of differentiation such as wnt signals

Brain in Health & Disease (9 decks)

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