Neuropath 3 Flashcards
What is TSE and what are the characteristics of it?
- Transmissible spongiform encephalopathy (TSE)
- Neurodegenerative diseases
- Rapidly progressive, always fatal
- Affect humans and animals
- Long incubation periods e.g. in PNG it took 45 years to develop disease
- Prion-only hypothesis widely accepted
Why is it refered to as spongiform changes?
These uniform changes are unique to prion disease and the appearance under the microscope is similar to the appearance of a sponge.
Is neuronal degeneration/loss/death the same as spongiform changes?
No, neuronal degeneration can be mirrowed with spongiform changes but are quite different. With neuronal loss we will see spaces (vacuolation)
Name the TSE diseases and which part of the brain we will see initial changes.
- Brain stem: scraple, BSE and chronic wasting disease
- Cerebellum: kuru
- Thalamus: fatal familial insomnia
- Cerebral cortex: classic CJD
Name the important human TSEs
- Kuru
- Creutzefeldt-Jakob disease (CJD) - associated with cannabilism in PNG
- Variant Creutzefeldt-Jakob disease (vCJD) - associated with made cow disease
- Gerstmann-Sträussler Scheinker Syndrome (GSS)
Name the main animal TSEs
- Scrapie
- Bovine Spongiform Encephalopathy (BSE)
- Chronic Wasting Disease (CWD)
What is the link between scrapies and humans?
- Sheep scrapies doesn’t affect humans but is transmissible to cows to cause BSE which can be transmitted to humans as CJD
Is culling an efficient way to manage scrapie?
No, the prion protein can lay dormant in soil for years, resulting in outbreaks years after infected individuals have been removed from the herd
Is/has scrapie been in Australia?
Yes, we are aware of 5 cases in VIC (atypical scrapie)
How do sheep get scrapie?
Ingestion of contaminated material (can stay in the environment for up to 15 years).
Dissemination of prions:
- Systemic
- lymphatic
- nervous system (most effective route)
Is Bovine spongiform encephalopathy (BSE) a big issue?
No, not anymore.
What are the possible causes of BSE?
The practice of feeding cattle rendered animal parts was implicated
Rendered material was from either:
* Scrapie infected sheep
* Cattle with spontaneous BSE
What clinical symptoms are assoicated with Chronic wasting disease (CWD)?
Weight loss
Behavioural changes
Excessive salivation
Difficulty swallowing
What clinical symptoms are assoicated with Chronic wasting disease (CWD)?
Weight loss
Behavioural changes
Excessive salivation
Difficulty swallowing
What is the main issue with CWD?
Wildlife resovoirs -> difficult to control
What is a prion?
- Shortened form of Proteinaceous infectious particles
- Prions are single molecules containing about 250 amino acids
- They are abnormal variants of proteins which normally occur in cells
- Prions have the ability to convert the normal forms that they come into contact with into abnormal forms
List some features of prions
- Prions are non immunogens and do not induce an immune response
- Prions are not easy to decompose biologically
- They are resistant to high temperatures & disinfectants
- Prions are resistant to digestion by proteases
Explain the prion hypothesis
- PrP is a normal cellular protein referred to as PrPc
- Diseased brain contains aberrant PrP which is referred to as PrPSc
- PrPSc has the ability to convert PrPc to itself
- A chain reaction follows, resulting in a cluster of tangled, nonfunctional proteins called plaques, which are aggregates of PrPSc in the brain
- PrPSc requires normal protein (PrPc) to produce more abnormal protein
If you inoculate strain A into species A what will happen? Compare this to injecting strain B into species A.
- If you inoculate strain A into species A – will keep getting same disease profile
- If you inject strain B into species A – will get similar disease profile
Explain the species barrier phenomenon.
If you inject prions from species B to a different species = shorten incubation period
Does prion disease affect all species?
Dogs (besides rottweilers) and rabbits are not affected by prion disease.
