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Flashcards in Parkinson's Disease Deck (125)
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What was parkinson's disease first described as?

"shaking palsy"
by British physician, James Parkinson



-progressively deteriorating neurological disorder
-hypokinetic or akinetic disease
-the clinical syndrome that arises from the degeneration of the basal ganglia
-the damage is to the substantial nigra (aka MAY NOT be b/c of loss of DA)
-PD=IPD; secondary parkinsonism


Parkinson's Disease

-the most common cause of parkinsonism
-idiopathic neurodegenerative condition caused by loss of dopaminergic neutrons in the substantial nigra


What is PD characterized by

-asymmetrical resting tremor
-bradykinesia (brady means slow and kinesis means movement)
-postural instability (shuffling along, bent over)


secondary parkinsonism

-secondary to a known cause
-similar to Parkinson disease, but the symptoms are caused by certain medicines, a different nervous system disorder, or another illness



-slowness or loss of normal motor function, resulting in impaired muscle movement
-literally "without movement" or without much movement



-estimated 4 million people living world wide with PD
-affects 1 in 100 over 65 (more than combined incidence of MS, muscular dystrophy and Lou Gehrig's disease)
-incidence increase as people age with average age of onset being around 60
-affects males to females 2:1
-development of IPD is inversely correlated with cigarette smoking and caffeine consumption



-its an important aa that gets taken up from blood into surrounding fluids that our brain is exposed to (CNS)-> BRAIN
-in this terminal, tyrosine gets taken up


what happens to tyrosine once it gets taken up by the substantial nigra neuron

-once taken up it is hydroxylated to L-dopa, then decarboxylated into DA


What happens to DA once it has been formed

-it gets packed into vesicles
-within the ion channels there is an influx of Ca/Na into the nerve channels-> inside becomes positive-> dumping of DA vesicles into the synaptic cleft
-on the post synaptic side, it binds to the D1 and D2 receptors on the putamen neurons


What happens when DA binds to the D1/D2 receptor on the putamen neuron (general)

-the pudamen neurons are located on the striatum
-this ends up increasing the amount of GABA, which actually ends up reducing the putamen activity
-this decrease in putamen activity ends up increasing activity of the ventrolateral thalamus, which controls movement


synaptic transmission (general)

-APs are produced via depolarization of the neuronal membrane due to an influx of Na through Na voltage-gated channels
-the produced AP propagates down the axon towards the pre--synaptic terminal
-arrival of the AP at the pre-synaptic terminal opens Ca channels in the PM
-the influx of Ca triggers the exocytosis of vesicles containing NT
-the NT enters the synaptic cleft and binds to receptors on the post-synaptic membrane
-following binding, the NT is cleaved and taken back up into the pre-synaptic terminal where it is recycled and stored in vesicles


DA synthesis

-tyrosine is taken up form the blood to the brain's ECF then into dopaminergic substantial nigra neurons via specific enzyme transporters
-it becomes hydroxylated to form L-DOPA, the DA precursor
-L-DOPA is then decarboxylated to make DA


Important anatomical structures involved

-basal ganglia
-substantia nigra
-ventrolateral thalamus (VLT)
-motor cortex
(-subthalamic nucleus)


basal ganglia

-controls complex movement s and has a part in motor learning-located at the base of the forebrain and composed of substantia nigra, striatum, sub-thalamic nucleus (and palladum)


substantia nigra

located in the midbrain with an important role in reward, addiction and movement
-input form all over the bran relayed via dopaminergic neurons to striatum



-composed of putamen and caudate nucleus and located below the cortex of the cerebrum
-major input site of the basal ganglia system-putamen neurons have both D1 and D2 receptors


Ventrolateral thalamus

-integration centre for basal-ganglionic and cerebellar impulses
-brought to the corticospinal system
-sends fibers to the percentile and supplementary motor cortices to initiate body movement


Motor cortex

-input signals are changed to output which leads to movement
-located in the frontal cortex of the brain
-ultimate highest order that needs to be stimulated in order to move (but if the VLT is stimulated, so will the motor cortex)


what NT is overstimulated in any addiction?



What functions is DA involved in?

-reward (motivation)
-pleasure, euphoria
-motor function (fine tuning)


What functions is serotonin involved in?



What are the 3 NT's all involved in Parkinson's disease?



What do these 3 NT's control?




-important in many brain fxns: motivation, cognition, learning, mood, attention, reward, sleep, & voluntary movement
-works via the direct/indirect path within the basal ganglia to initiate movement
-insufficient DA biosynthesis causes parkinson's where a person loses the ability to execute smooth controlled movement


How much DA function must be lost before it manifests as Parkinson's?



Where are certain areas where problems could lead to DA loss and therefore Parkinson's?

-presynaptic production
-postsynaptic effect (receptors)
-synaptic cleft effect (destruction)

-lack of DA (from an inability to be produced or inability to be secreted)
-lack of receptors/ inability of DA to bind to receptors
-over-producing amount of enzyme that chews up all the DA therefore isn't allowed to work


What is the relationship between Ach and DA?

-antagonistic NTs (Ach excitatory, while DA is inhibitory)


What happens to Ach when there is less than normal DA

-if dopaminergic cells are destroyed, no DA released to compete and Ach runs out of check


What does too much Ach cause?

-it causes over activity of cholinergic neurons
-leading muscles to contract but as there is excess Ach, muscles cant repolarize and will remain contracted