L6 - Glia and Multiple Sclerosis Flashcards Preview

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

Flashcards in L6 - Glia and Multiple Sclerosis Deck (36):
1

What proportion of brain is neurons

10%

2

What other cells make up the brain?

Glia
blood vessel
astrocytes
oligodendrocytes
microglia

3

When do glial cells first come about?

Last, after the neurogenesis of neurons

4

What do astrocytes do?

Takes glucose from capillary and gives it to neuron

5

What do astrocytes do at the synaptic cleft?

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

6

Why does glycolysis have to occur in astrocytes?

Used for Na ATPase and proton motive force

7

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

Glycolysis makes lactate
Neurons cannot use glucose very well

8

How is the glutamate transferred back into the neuron?

Using ATP to turn it into glutamine then goes in

9

What does high Ca in astrocytes do?

Leads to glutamate release

10

What happens to astrocytes during a stroke?

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

11

What do oligocendrocytes do?

Wrap up axons in myelin sheath

12

What are the components of the myelin sheath?

Proteolipid proteins
Myelin basic protein

13

How do oligodentrocytes migrate?

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

14

WHere do microglia arise from?

macrophages outside the CNS

15

What are are the features of microglia?

Tidy up any damage
Phagocytic
Antigen presenting cells

16

What is gliosis?

Astrocytes and microglia forming scar tissue

17

How are microglia led to the place of damage?

TNFa

18

Why is HIV such a bad disease?

infects microglia

19

What are the features of MS?

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

20

What does a scan of aNn MS patient show?

Lesions where white matter has been destroyed

21

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

Hypothesis on sunlight exposure or day length

22

What kind of genes are generally mutated in MS?

T cell related genes

23

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

Possibly associated with virus'
Sunlight, solvents, pollution, temp

24

What is the t cell model for MS?

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