topic 8 (neurodegeneration) lecture 2 & 3(parkinsons) Flashcards
who originally described parkinsons as shaking palsy?
James Parkinson
what is parkinsons prevalence?
1 in 500
what is disease duration
incidence rates is 1/12 of prevalnce this indicates disease duration is approx 12 years
how many new cases of parkinsons is there each year in the uk?
500
is it more common in men or women?
25% more common in men
what are 3 diagnostic symptoms?
shaking that only occurs at rest
slowness of moevement
muscle stiffness
what scans may be used?
SPECT scans similar to PET
what are 4 motor symptoms?
rigidity and tremor in extremities and head
forward tilt of body
shuffling gait
reduced arm swing
what are 6 non motor symptoms?
impaired memory
fluctuating attention
impaired perception
enhanced distractibility
mood problems
dementia
what are risk factors?
- AGE - affects 1% 60 yrs old but 5% of 85yr olds
- GENDER- men more likely. could be less oestrogen or increased head trauma
- FAMILY HISTORY
- ETHNICITY
- HEAD TRAUMA
- ENVIRONMENTAL PESTICIDES
what are changes in the brain in PD
- loss of dopaminergic neurons
- 80% in the substantia nigra compact
- 50% in the ventral tegmental area
-Lewy bodies- abnormal clumps of alpha synuclein
impact of loss of dopamine
- dopamine neurons in the substantia nigra compact send their axons to the dorsal striatum in the nigrostriatal pathway
- dopamine enters the striatum and feeds into the limbic associative sensory and motor loops
- dopamine favours the direct pathway which favours movement so loss of dopamine= loss of movement
is the late onset of parkinsons disease genetic and what type?
yes it is considered to be autosomal dominant
what is the genetic type of early onset PD?
autosomal recessive
what are 6 processes disrupted or affected in parkinsons disease?
protein aggregation- seen by lewy bodies
protein and membrane trafficking
neurite structure
ubuiquitim-proteasome system
mitochondria function
lysosome function
How is oxidative stress related to parkinsons disease?
- oxidative stress is a state of imbalance between the production of reactive oxygen species and their clearance from within the cell.
- excess reactive oxygen species can cause damage to cell DNA lipids and proteins
- dopaminergic neurons are 4x more susceptible to ROS damage, possibly due to high calcium loading
- postmortem PD brains show decrease in antioxidant activity and evidence of ROS mediated damage to lipids and DNA
- calcium channel blockers which reduce oxidative stress appear to be effective
How does inflammation relate to parkinsons disease?
- neuroinflammation is a feature
- use of antiinflammatory information is associated with a reduced risk of PD
- not clear whether reaction or cause to the condition
what is thought to be the spread of PD?
- pathology starts in the peripheral nervous system, olfactory system and medulla
- it then spreads up through the spinal cord and brain up to multiple cortical regions
- this has been theorised by looking at the location of lewy bodies that act like a prion disease
- its thought that dopaminergic neurons could be particuarly prone to death from lewy bodies
when considering multifactoral pathogenesis, what are the 3 main proposed causes for loss of dopamine neurons?
genetic alterations
oxidative stress
environmental factors leading to mitochondrial dysfunction
what are 4 ways of reducing loss of dopamine in parkinsons?
increase production
increase release
mimic action
decrease reuptake
decrease breakdown
what are 3 treatments for early PD, effectiveness and likelyhood of motor complications
LEVODOPA
- increasews production
- good effect
- increases risk of motor complication
DOPAMINE ANTAGONISTS
- mimic effect
- moderate effect
- decrease motor complication risk
MAO-B INHIBITOR
- prevent breakdown
- limited effect
- reduced motor complications
how does deep brain stimulation treat parkinsons disease?
- uses an electrode to stimulate parts of the brain
- helps synchronise basal ganglia pathways
how can transplantation treat parkinsons?
- foetal DA cells can be transplanted into the striatum
- they form connections to host neurons
- this provides some signs of restoration of function
- due to these ethical issues stem cells may be used instead
- issues with stem cells include controlling differentiation and division appropriately
