Lecture 6 Flashcards
(34 cards)
What three diseases are glia diseases?
Multiple sclerosis
Ischemia
Epilepsy
What five approaches would you take when you encounter a disease?
- Symptoms
- Anatomy
- Epidemiology
- Genetics
- Animal Models
What cell types make up the brain?
- Neurons (only 10%)
- Astrocytes
- Oligodendrocytes
- Microglia
Where do nuerons start and migrate from-to?
The base of the brain and migrate to the cortex
Where do glia start and migrate from-to?
The basement membrane and migrate to the cortex
What roles do astrocytes play?
Provide a bridge between the capillaries and the neurons - to transfer nutrients for neuron function
Also take up glutamate and Na+ down the Na gradient during transmission across to stop all acting on postsynaptic membrane. The glia then remove the sodium using Na+K+ ATPase, which requires glycolysis. Lactate product from glycolysis given to neuron for energy. Use energyto break down the glutamate to glutamine which is also given back to the neuron for the next signal
What type of activity do glia cells show?
Calcium waves to regulate feet on the capillary
How are astrocytes implicated in strokes?
Lack of oxygen to astrocytes means they cannot deal with glutamate and actually release all of their own glutamate causing a stroke
What role do schwann cells play?
They form the myelin sheath, mainly made up of P0- important for speeding up signal transduction in fast acting neurons
What cells sheath neurons in the CNS?
How?
Oligodendrocytes
Have proteolipid and myelin basic proteins making up the sheath
How is motility of oligodendrocytes promoted?
PDGF
How do astryocytes migrate to retina neurons?
Chemorepellant netrin causes them to move and they follow the axon which has already reached the retina
Which axonal signals are involved in myelination and ensheathment?
Neurotransmitters
NCAM
N-cadherin
When is Oligodendrogenesis occuring?
From develpoment and into adulthood when learning new complex tasks, e.g. piano
Where do microglia arise from?
What is there role?
Arise form macrophages outside the CNS
Following chemotactic signals and enter active phagocytic state
What is a consequence of microglia and astocyte action?
Gliosis - formation of scar tissue
Now seen in HIV which infects microglia
What is MS characterised by?
Demyelination of the CNS causing weak movement, blurred vision to begin with and then later bladder dysfunction and fatigue. Relapses in 85% of cases. High levels of IgG
How long can it take for a lesion to cause relapse?
Up to 10 years
What is the epidemiology of MS?
1.2 : 1000 in UK
Some suggestion that it is latitude based. Common in UK, parts of europe, america and new zealand. In america more common in caucasians. Increasingly common in females. 20-30% occurrence between identical twins, only 2-5% between fraternal same-sex twins.
What have GWAS studies shown about MS?
Many T-cell related genes and the HLA-DRB1 gene on chromosome 6p21
What environmental factors have been implicated?
- Antibody against myelin like protein due to infection
- Chylmadia infection (not repeated)
- Epstein-barr virus as a child (not repeated)
- Sunlight (vitamin D), solvents, pollution, temperature, rainfall
What work has been with animal models?
- Inject with factors to create microglial infection to make experiemental allergic encephalomyelitis (EAE) mouse model
- Metalloproteinases can destroy blood brain barrier allowing lymphocytes to enter. T cells are then activated against myelin
What are the suggested models of MS?
- T cell invasion and inflammation causing microglia action against myelin
- Oxidative stress due to reduction in myelination causing excess axonal ionic flux and more superoxide formation
- Reduction in blood flow causes lack of oxygen and intensifies superoxide production
Why is cannabis useful in MS?
Why is it not the best treatment?
Relieves muscle stiffness, body pain and muscle spasms.
It only relieves the symptoms but is not disease modifying
