Demyelinating disorders Flashcards
How much of the brain is grey matter?
50% Grey matter
50% White matter
Billions of cells communicate
Myelin sheath in key to rapid communication
______ myelinate neurones in the CNS?
Oligodendrocyte
what (developmentally) does myelination begin?
Myelination begins in third trimester
Rapid increase in myelination at birth
Continues throughout life
Where do oligodendrocytes come from in CNS?
Oligodendrocyte precursor cells distributed in CNS (green stain)
Proliferate and differentiate into oligodendrocytes
Form myelin sheaths
How is myelin wrapped around axons?
specialised plasma membrane - Concentrically laminated membrane structure
Lamella formed from fusion of opposed inner leaflets of plasma membrane
No intervening cytoplasm
How is myelin wrapped around axons?
specialised plasma membrane - Concentrically laminated membrane structure
Lamella formed from fusion of opposed inner leaflets of plasma membrane
No intervening cytoplasm
What is the connection between oligodendrocytes and the myelin wrap they give to CNS neurones?
Pedicle
a myelinating cell myelinates one neuron. What type of cells are they?
PNS Schwann cell myelinates one PNS neuron
Are all axons myelinated?
No, only large ones
How large does an axon need to be in order to be myelinated in the CNS?
In CNS axons >0.2µm myelinated
How large does an axon need to be in order to be myelinated in the PNS?
In PNS axons>1-2µm myelinated
The ______ (larger/smaller) the axon, the _______ (fewer/more) wraps of myelin?
The larger the axon, the more wraps of myelin
What is the ratio between axon diameter and total nerve fibre diameter?
Ratio between axon diameter and total nerve fibre diameter (axon plus myelin) is 0.5-0.9, optimal 0.77
Length of myelin sheath approx _____mm in PNS with gaps between sheaths
Length of myelin sheath approx 1mm in PNS with gaps between sheaths (Nodes of Ranvier)
Length of myelin sheath approx _____mm in PNS with gaps between sheaths
Length of myelin sheath approx 1mm in PNS with gaps between sheaths (Nodes of Ranvier)
How is spiral wrapping done so precisely?
Myelination is thought to be dependent on neuronal activity
Communication via neuro-glial signalling molecules (gliotransmitters)
In PNS how is myelination done?
Proteins expressed on axon surface interact with receptors on glial cells (eg neuroregulin 1 type 3 protein in PNS and Erb β receptors)
They have role in cells then differentiating into schwann cells to produce the myelin sheath
Heavily myelinated fibres have high level of proteins
Heavily myelinated fibres have _______ (low/high) level of proteins ?
Heavily myelinated fibres have high level of proteins (axon surface to glial cells)
Summarise 3 functions of myelin
Reduces loss of charge across the axon
Speeds up transmission of the action potential along the axon
Unmyelinated fibres 0.5-2m/s
Myelinated fibres 70-100m/s
Increases efficiency of the electrical transmission
Less ion channels needed, clustered at nodes of Ranvier
How do nodes of Ranvier help to propagate action potentials?
Some of the current propagated by the action potential spreads passively to the next node due to the insulating effect of myelin (no/few channels increases membrane resistance to charge leakage) and
What can damage myelin?
Mechanisms of damage
Brain injury
Ischaemia
Toxins
Metabolic
Neurodegenerative
Infective
Immune based
what are “leukodystrophies”
Failure to myelinate: leukodystrophies
define demyelination
Damage and loss of myelin sheath is termed demyelination
do steroids help MS relapses?
They speed them up but do not alter the course of the nerve damage, just resolve the flare-up faster
What is the direct pathological consequence of demyelination
Loss of myelin leads to slowing/blocking of nerve messages
What are some of the symptoms of demyelination?
1
2
3
4
5
6
7
8
9
10
Visual impairment
Changes in cognition
Speech impairment
Balance problems
Incoordination
Sensory symptoms
Weakness
Bladder/bowel problems
Pain
Fatigue
Core info about MS?
Central nervous system demyelination
Immune based disorder
Does MS affect men more than women?
3 female:1 male
What causes MS?
Cause: unknown!
Links to northern hemispheres…
Genetic 30%
Environmental: sun/vit d exposure
Infection ?EBV
Cigarette smoking
Obesity in early life
Summarise mechanism of MS damage
-cells implicated
-Relapse/remmission pattern
Immune cells enter the brain and attack myelin (T cells)
Relapses = demyelination
Remissions = remyelination but may be incomplete
Failure of remyelination = ongoing symptoms and disability
What’s the difference between primary progressive and secondary progressive disease in MS
Can go on to a progressive phase (secondary progressive MS) (if it does not it was not MS)
Some people have primary progressive disease from start
How does MS lead to disability?
The location of the damage correlate to the symptoms, not the nature of the damage! NEUROLOGY CORE CONCEPT
what damage can be seen on the spinal cord of this MRI?
Grey area of sclerotic damage (scarring)
