Lecture 9 - Diseased Axons Flashcards
What is a demyelinating disease?
Disease of the nervous system in which the myelin sheath of neurons is damaged
Impairs conduction of signals in the affected nerves
What are functional effects of demyelination?
Both positive and negative
What are examples of negative demyelination?
Loss of sensation
Loss of visual fields
Motor domain paralysis
What does multiple sclerosis affect and why?
Walking
Axons in the spinal cord that control walking are longer than others in CNS
More likely to be affected by demyelinated lesions
What are examples of positive symptoms?
Paraesthesia (odd sensation: pins and needles)
Neuromyotonia
Titnius
Pain (complicated sensation)
What is Neuromyotonia?
Muscle contraction brought about by spontaneous activity in nervous system
How do axons conduct impulses?
High safety factor
What does it mean sheen there is reduced safety factor (damage to axons)?
The probability of an impulse to get through a region of damage is <1
What are ways of generating experimental demyelination?
- Diphtheria toxin is used
- Natural detergent
- Ethidium bromide
- X-rays
Diphtheria toxin
Spinal root axons are exposed to Diphtheria by intrathecal Injection
Blocks protein synthesis in the schwann cells
Produce demyelination of spinal root axons
The use of a natural detergent?
Dissolves the myelin and demyelinates it in the peripheral nerve
Myelin is many layers of cell membrane
What is Ethidium bromide?
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
What holds the resting potential?
Capacity
What happens when there is an inward current?
A spread of depolarisation will occur which will change the amount of charge on membrane capacity
What is Holmes law?
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
What is a contour map?
Plots of current density
According to distance and time
How are inward currents plotted?
continuous lines
What happens when there is greatest current density?
There are lots of lines coming toward the middle
Where are outward currents?
Between the nodes
Indicated by dotted lines
What is a normal axon?
6 millimetres in 0.1 seconds
Very easy
What can occur at demyelinated region of axon?
Spontaneous activity
What is evoke potential (VP)?
A potential event that can be recorded of the surface of the head non-invasively
What does myelinated axon have?
Microanatomical circumsted regions
What are key characteristics of node?
High density of Na+ channels to allow impulse impulse conduction
What happens at the paranode?
Where terminal loops of myelin, stick, adhere and are stabilised to the axon
What stabilises the terminal loops?
Adhesion molecules
What do you not find in mammals?
Fast K+ channels
What happens when the myelin is taken off?
The fast K+ channels help the stabilise the membrane potential of axons
Stop impulse propagating through the region where the myelin has come off
Juxtaparanode
In normal axons there is fast k+ channels
KV1.1 and KV1.2
At the node of Ranvier, under normal circumstance what kind of axon is present than the internode ?
Narrower axon
Why does node of Ranvier have narrower axon?
More phosphorylation of neurofilaments inside the axon
Occupy more space
Makes internode more fatter
Easier to drive current through.
Cell adhesion molecules
Important in myelinated nerve
What are cell adhesion molecules expressed by?
Both the axon and myelinating cell
Sticking together and holding the structure
Neurofasin
Hold microvilli next to the node
Where are neurofasin 186 expressed in?
Paranode of myelin
Contacts contactin and Casper
How many main channel found in the node of Ranvier?
6
What is expressed in paranode in mammal?
Casper
Contactin
What is myelin protein p0 a structural component of?
Peripheral myelin
CAM
What happens when P0 is knocked out?
Desmyelinating neuropathy is produced
Peripheral myelin can’t form properly
What does P0 exhibit?
Haploninsifficiency
What happens when there is only one P0 functional gene?
Late onset neuropathy that mimics CMT1B
What is CMT1B?
Charcot-Marie-Tooth disease Type 18
What is PMP22?
Homophilic CAM
What are point mutations of PMP22?
Trembler and Trembler-J
What does overexpression of PMP22 in transgenic animal mimic?
CMT1A