Lecture 9 - Diseased Axons

Question 1

What is a demyelinating disease?

Answer 1

Disease of the nervous system in which the myelin sheath of neurons is damaged
Impairs conduction of signals in the affected nerves

Question 2

What are functional effects of demyelination?

Answer 2

Both positive and negative

Question 3

What are examples of negative demyelination?

Answer 3

Loss of sensation
Loss of visual fields
Motor domain paralysis

Question 4

What does multiple sclerosis affect and why?

Answer 4

Walking
Axons in the spinal cord that control walking are longer than others in CNS
More likely to be affected by demyelinated lesions

Question 5

What are examples of positive symptoms?

Answer 5

Paraesthesia (odd sensation: pins and needles)
Neuromyotonia
Titnius
Pain (complicated sensation)

Question 6

What is Neuromyotonia?

Answer 6

Muscle contraction brought about by spontaneous activity in nervous system

Question 7

How do axons conduct impulses?

Answer 7

High safety factor

Question 8

What does it mean sheen there is reduced safety factor (damage to axons)?

Answer 8

The probability of an impulse to get through a region of damage is <1

Question 9

What are ways of generating experimental demyelination?

Answer 9

1. Diphtheria toxin is used
2. Natural detergent
3. Ethidium bromide
4. X-rays

Question 10

Diphtheria toxin

Answer 10

Spinal root axons are exposed to Diphtheria by intrathecal Injection
Blocks protein synthesis in the schwann cells
Produce demyelination of spinal root axons

Question 11

The use of a natural detergent?

Answer 11

Dissolves the myelin and demyelinates it in the peripheral nerve
Myelin is many layers of cell membrane

Question 12

What is Ethidium bromide?

Answer 12

Dye binds to DNA
When it interacts with UV light it fluorescence
It is toxic it can be used to demyelinate dorsal column axons by intraspinal injection
Kills oligodendrocyte that produces myelin

Question 13

What holds the resting potential?

Answer 13

Capacity

Question 14

What happens when there is an inward current?

Answer 14

A spread of depolarisation will occur which will change the amount of charge on membrane capacity

Question 15

What is Holmes law?

Answer 15

If we know the voltage of v1 and v2 and we know what the resistance between them, we will know what the current is flowing between the two points

Question 16

What is a contour map?

Answer 16

Plots of current density

According to distance and time

Question 17

How are inward currents plotted?

Answer 17

continuous lines

Question 18

What happens when there is greatest current density?

Answer 18

There are lots of lines coming toward the middle

Question 19

Where are outward currents?

Answer 19

Between the nodes

Indicated by dotted lines

Question 20

What is a normal axon?

Answer 20

6 millimetres in 0.1 seconds

Very easy

Question 21

What can occur at demyelinated region of axon?

Answer 21

Spontaneous activity

Question 22

What is evoke potential (VP)?

Answer 22

A potential event that can be recorded of the surface of the head non-invasively

Question 23

What does myelinated axon have?

Answer 23

Microanatomical circumsted regions

Question 24

What are key characteristics of node?

Answer 24

High density of Na+ channels to allow impulse impulse conduction

Question 25

What happens at the paranode?

Answer 25

Where terminal loops of myelin, stick, adhere and are stabilised to the axon

Question 26

What stabilises the terminal loops?

Answer 26

Adhesion molecules

Question 27

What do you not find in mammals?

Answer 27

Fast K+ channels

Question 28

What happens when the myelin is taken off?

Answer 28

The fast K+ channels help the stabilise the membrane potential of axons
Stop impulse propagating through the region where the myelin has come off

Question 29

Juxtaparanode

Answer 29

In normal axons there is fast k+ channels

KV1.1 and KV1.2

Question 30

At the node of Ranvier, under normal circumstance what kind of axon is present than the internode ?

Answer 30

Narrower axon

Question 31

Why does node of Ranvier have narrower axon?

Answer 31

More phosphorylation of neurofilaments inside the axon
Occupy more space
Makes internode more fatter
Easier to drive current through.

Question 32

Cell adhesion molecules

Answer 32

Important in myelinated nerve

Question 33

What are cell adhesion molecules expressed by?

Answer 33

Both the axon and myelinating cell

Sticking together and holding the structure

Question 34

Neurofasin

Answer 34

Hold microvilli next to the node

Question 35

Where are neurofasin 186 expressed in?

Answer 35

Paranode of myelin

Contacts contactin and Casper

Question 36

How many main channel found in the node of Ranvier?

Answer 36

6

Question 37

What is expressed in paranode in mammal?

Answer 37

Casper

Contactin

Question 38

What is myelin protein p0 a structural component of?

Answer 38

Peripheral myelin

CAM

Question 39

What happens when P0 is knocked out?

Answer 39

Desmyelinating neuropathy is produced

Peripheral myelin can’t form properly

Question 40

What does P0 exhibit?

Answer 40

Haploninsifficiency

Question 41

What happens when there is only one P0 functional gene?

Answer 41

Late onset neuropathy that mimics CMT1B

Question 42

What is CMT1B?

Answer 42

Charcot-Marie-Tooth disease Type 18

Question 43

What is PMP22?

Answer 43

Homophilic CAM

Question 44

What are point mutations of PMP22?

Answer 44

Trembler and Trembler-J

Question 45

What does overexpression of PMP22 in transgenic animal mimic?

Answer 45

CMT1A