Parkinson's Disease Flashcards
Describe what happens in the substantia nigra neurons
- Tyrosine is HYDROXYLATED to become L-dopa
- L-dopa is decarboxylated to become dopamine
- Dopamine is packaged into vesicles
- Ca2+ influx stimulates the exocytosis of the vesicles
- DA crosses the cleft and goes to the putamen neurons in the striatum
Descibe the epidemiology of parkinson’s disease.
- 4 million people affected worldwide
- incidence increases with age (around 60)
- affects males to females 2:1
- development of IPD inversely related with smoking and caffeine consumption
What signals the Ca2+ channels to open?
- the arrival of the AP to the presynaptic terminal
- influx causes the release of the NTs (Dopamine)
What is the basal ganglia composed of?
What does it control?
Composed of:
- substantia nigra
- striatum
- subthalamic nucleus
The basal ganglia controls complex motor movements and plays a part in motor learning
Where is the substantia nigra located?
What is its role?
- located in the midbrain
- important role in reward, addiction and movement
What is the striatum composed of?
Where is it located?
Name its receptors.
- putamen neurons
- located below the cortex of cerebrum
- D1 and D2 neuron
What does VLT stand for?
What is its role?
What is its mechanism?
- Ventrolateral thalamus
- role is to control the motor cortex for movement
- DA stimulates putamen neurons, PNs then act on the VLT to produce movement
What happens in the motor cortex?
- input signals are converted to output which produces movement
- located in frontal cortex of brain
Why does smoking help with Parkinson’s?
because it releases DA
What brain functions involve DA?
- reward
- voluntary movement
- motivation
- cognition
- learning
- mood
- attention
- sleep
How is DA related to Parkinson’s?
A parkinson’s pt has insufficient DA, which leads to loss of the ability to execute smooth controlled movements
Parkinson’s disease manifests when _______ of DA function has been lost.
~ 80%
Ach is excitatory, DA is inhbitory.
Thus, this makes these NTs ______________ ______________.
antagonistic neurotransmitters
What happens when there is an excess of Ach?
- overactivity of cholinergic neurons
- muscles contract
- due to decreasing levels of Ach, muscles stay contracted
- pt becomes “locked in stone”
In normal motor systems, how is GABA release regulated?
By the binding of DA to receptors
How does a decrease in DA levels affect GABA?
- Decreased DA increases GABA
- too much GABA doesn’t allow the VLT to be stimulated
- no movement
- pt becomes partially or totally paralyzed
What receptor does DA bind to on the direct movement pathway?
D1 on putamen neurons
What happens in a normal pt when DA binds the the D1 receptor?
- causes an initial increase in GABA, putamen neurons can’t fire
- since PNs produce GABA, levels will decrease
- less inhibition to VLT
- body movement
What happens to the direct pathway in PD pts?
- insufficient DA
- DA doesn’t bind to D1 receptors
- GABA will decrease
- Firing of D1 neurons increases
- D1 neurons release GABA, less VLT transmission to motor cortex
What is IPD?
What is its etiology?
- idiopathic Parkinson’s disease
- AKA primary PD
- caused by the degeneration of DA in the substantia nigra
Genetics factors
Oxidative Stress
- free radicals generated from DA metabolism
- lack of antioxidant defense
Excitotoxicity
- nerve cells are damaged or killed due to excess glutamate
- DA not present to inhibit glutaminergic stimulation
What is secondary PD?
Causes?
- inability to produce DA
- inability to secrete DA
- inability of DA to bind to receptors on putamen neurons
- drugs
- toxins
- infections
- head trauma
Describe the mechanism of drug-induced PD.
- certain drugs are DA antagonists
- they block DA receptors and output from the substantia nigra
- onset is abrupt, sx symmetrical
- cause Parkinson’s signs (rigidity, hypokinesia, resting tremor)
ex. antipsychotics, CCBs
How do CCBs cause drug-induced PD?
- Ca2+ is needed to release the DA vesicles from substantia nigra
- if blocked, no DA binds to putamen neurons
- no movement
How do toxins contribute to secondary PD?
- pesticides or heavy metals (iron and manganese) can cause irreversible damage to the dopaminergic neurons in the SN
