Pharmacology of the Basal Ganglia Flashcards
Parkinsons disease pathology;
Where in the brain is dopamine produced? [1]
substantia nigra
Which of the following is the substantia nigra?
14
Which of the following is the substantia nigra?
27
Which of the following is the substantia nigra
A
B
C
D
E
Which of the following is the substantia nigra
A
B
C
D
E
What structure is found in neurons that is characteristic of Parkinsons (and other conditions such as dementia)
Lewy bodies
Which protein is found in Lewys bodies?
protein α-synuclein
Name the staging system used to classify Parkinson’s disease [1]
What is the difference between [] stage 1 & 2 to [] Stage V & VI? [1]
The Braak staging of Parkinson’s disease
Braak stage 1 & 2
* pathological changes occur in the medulla oblongata and olfactory bulb
Braak stages 5 and 6:
* the cortical regions eventually become affected
Which stages of Braak staging of Parkinsons are symptoms most likely to develop?
Braak 1 & 2
Braak 3 & 4
Braak 5 & 6
Which stages of Braak staging of Parkinsons are symptoms most likely to develop?
Braak 1 & 2
Braak 3 & 4
Braak 5 & 6
What type of imaging can be used to monitor dopaminergic nigral cell loss? [1]
dopamine transporter (DaT) - Dat Scan
Describe in detail the classic triad of motor symptoms of Parkinson’s [3]
Bradykinesia
* poverty of movement also seen, sometimes referred to as hypokinesia
* short, shuffling steps with reduced arm swinging
* difficulty in initiating movement
Tremor
* most marked at rest, 3-5 Hz
* worse when stressed or tired, improves with voluntary movement
* typically ‘pill-rolling’, i.e. in the thumb and index finger
Rigidity
* lead pipe
* cogwheel: due to superimposed tremor
State 5 non-motor features of Parkinson’s disease
- micrographia
- olfactory dysfunction
- depression
- psychotic symptoms
- cognitive dysfunction
- dementia (late phase)
- sleep disturbance
- bladder and bowel dysfunction
- speech and language changes
Describe the difference in onset of symptoms between motor & non-motor Parkinson’s symptoms
Non-motor features may precede by 12-15 years: likely to involve regions of peripheral and central nervous system
Describe the difference in onset of symptoms between motor & non-motor Parkinson’s symptoms
Non-motor features may precede by 12-15 years: likely to involve regions of peripheral and central nervous system
What is the name for the scoring scales used for disability associated with PD? [1]
What is difference between 0% and 100%? [1]
Schwab and England Activities of Daily Living
0%: Vegetative functions
100%: Completely independent - can do chorse without slowness, difficulity or impairment
The genetic link between familial PD is due to a link between which protein? [1] Which gene codes for this protein? [1]
Is PD genetic or environmental? [1]
genetic link with the protein alpha-synuclein coded by SNCA (duplications or triplications cause autosomal dominant familial PD)
disease emergence may be due to interactions environment x genes
Describe the link between mitochondrial toxicity and dopaminergic neurons [1]
What process is diruspted as a result of ^ [1]
The compound MPTP is a toxin which can be transformed into the metabolite MPP+ which is neurotoxic for dopaminergic neurons
Dysfunction of complex I of the mitochondrial respiratory chain
can lead to increased oxidative stress
Which enzyme is critical in the dopamine oxidation process? [1]
What are the products of the dopamine oxidation process? [1]
Monoamine oxidase - break down of dopamine can create free radicals (e.g. H2O2
COME back to dopminergic pathways in teh CNS
Describe the mechanism of creation of dopamine [3]
L-tyrosine –> L-Dopa (Decarboxylated to create..) –> Dopamine
Describe the mechanism of dopamine metabolism [3]
Dopamine –> DOPAC –> Homovanillic acid
Dopamine binds to which two receptors? [2]
What are the subtypes of these receptors? [5]
D1 Family Receptors:
* D1 & D5 subtypes
D2 Family Receptors
* D2, D3 & D4 subtypes
Under normal conditions, what does the activation of D1 & D2 receptors cause? [2]
D1 receptors are found on the striatal neurons that give rise to the direct pathway: GO pathway
D2 receptors are found on the neurons whose axons form the indirect pathway. NO GO PATHWAY
