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Transcript
Parkinson’s Disease
storyboard
Possible Intro Scenario
• As an resident at Normal Hospital, you are beginning
your rotation in neurology. Your supervisor, Dr. _____,
mentions that one of the patients coming in today,
________, suffers from Parkinson’s Disease. She
recommends that you familiarize yourself with disease,
including the cause, symptoms, and latest research. She
informs you that the hospital’s electronic medical
reference will contain everything you need to get started
and suggests that proceed to the ________ room to
explore the EMR on the computer there.
• Student then proceeds to the room mentioned above.
Once at the computer in the _____
room…
• Student clicks the computer on and is greeted with the
similar menu as the stroke lab, including the Parkinson’s
Disease tutorial, EMR, lab notebook, and protocol.
• The Parkinson’s Disease tutorial should include the
following items…
–
–
–
–
–
–
–
Symptoms of PKD
Dopamine in the brain
Neuron transmission
Dopamine tone and Parkinson’s Disease
Maintenance of Dopamine Tone
Research in Parkinson’s Disease
The Bucket Theory
Remaining Issues
• Need to figure out computer screen format for tutorial.
• Need to figure out what needs to go in the EMR.
• Need to determine if questions will be multiple choice or
free form.
• Need to determine what will go in the electronic lab
notes.
• Need to determine how deep to get into brain anatomy.
• Need to figure out questions/activity for the Bucket
theory and computer program animations.
• Need to determine how to transition from human brain to
rat brain.
• Need to figure out final product.
Symptoms of PKD
• Students watch a video of a PKD patient and are
asked to check off the symptoms they see. Once
they correctly answer the checklist, the
symptoms should go in their lab notes
(electronically).
• Symptoms should include…
–
–
–
–
–
Tremor
Bradykinesia (slowed motion)
Rigid muscles
Impaired posture/balance
Loss of automatic motions
Additional Symptoms
• There are symptoms that students can not
observe from the video. These include speech
changes and dementia. These two symptoms
should be mentioned at some point in time.
Perhaps they could be added after the checklist
such as in the following statement?
• Well done! You’ve identified all of the observable
characteristics of Parkinson’s Disease. Please
realize that patients suffering from Parkinson’s
Disease will also often exhibit speech changes
and dementia.
Dopamine in the Brain
• Parkinson’s Disease is caused by the loss
of dopamine neurons in the substantia
nigra of the brain. These dopamine
neurons originate in the substantia nigra
and terminate in the striatum, where they
release dopamine to activate different
activities.
• Proceed to the activity
Dopamine in the brain Activity
• Click on the brain below to see what areas
of the brain dopamine affects. Students
are then either asked to list these areas of
the brain or choose from a checklist.
Students could then match the PKD
symptoms to the brain areas they think
they control. Again there could be a “check
your answer” section (similar to the EMR).
Dopamine Pathway in the Brain
Dopaminergic pathways of the human brain in normal condition (left) and
Parkinson's disease (right). Red Arrows indicate suppression of the target,
blue arrows indicate stimulation of target structure.
Another look at the pathway
Neuron Transmission
• In order to understand how the symptoms of
PKD occur, one must understand how DA is
transmitted in the brain.
• Students should then do the 2 activities.
• Questions about this…
– Should the answers to the questions show up as
multiple choice?
– Should the answers be recorded in the lab notes once
answered correctly?
– Should there be information in the EMR to assist with
the answers?
Neuron Transmission Activity 1
• Watch animation of the neuron synapse
and answer the following questions:
– How does dopamine transmit a signal from
the axon of one neuron to the dendrite of
another?
– What happens to dopamine molecules once
the signal has been transmitted?
Neuron Transmission Activity 2
• Watch the animation of a group of DA
neuron synapses and answer the following
questions:
– When DA molecules are released, one of two
things will happen to them. What are they?
– What cells do you see here besides DA
neurons? What are their functions?
– What cells do you see here besides DA
neurons? What are their functions?
Dopamine Tone and Parkinson’s
Disease
• The density of DA molecules around the
neurons is called dopamine tone. The amount of
them is also referred to as the dopamine tonic
level. The dopamine tone is thought to be
responsible for enabling dopamine to perform its
functions efficiently. One of the major
breakthroughs in the study of Parkinson’s
Disease was the discovery of the relationship
between DA neuron concentration, DA tone, and
PKD symptoms.
• Students are then instructed to proceed to the 2
activities.
Dopamine Tone and Parkinson’s
Disease Activity 1
PD Symptoms
Symptoms of Parkinson's Disease
90
10
0
80
70
60
50
40
30
20
5
10
15
Symptoms of
Parkinson's Disease
Percentage of Dopamine Neurons
At what percentage of DA neuron loss do PKD symptoms begin to occur?
PKD is not diagnosed until symptoms occur. At that point, what the percentage of
DA neurons does the victim have left?
Dopamine Tone and Parkinson’s
Disease Activity 2
Dopamine Tone
Percentage of Dopmaine Tone
120
100
80
60
Dopamine Tone
40
20
100
90
80
70
60
50
40
30
20
15
10
5
0
0
Percentage of Dopamine Neurons
At what DA neuron concentration does DA tone begin to decrease?
How does this compare to the DA neuron concentration at which PKD symptoms
begin to occur?
Summarize the relationship between DA neuron concentration, DA tone, and PKD
symptoms.
Maintenance of Dopamine Tone
• As can be seen from previous studies, DA tone begins to
fall after about an 80% loss of DA neurons. At that same
point, PKD symptoms begin to become visible. Scientists
were not surprised to find a correlation between these
factors. What did surprise them was the large
percentage of DA neurons and individual could lose and
still seem to function normally. How is DA tone
maintained despite the loss of so many DA neurons?
The answer to this question is currently unknown;
however, two scientists have come forward with
hypotheses as to how the maintenance of DA tone is
possible in the face of the loss of so many DA neurons.
Introduction to Garris’ work
• Dr. Paul Garris has proposed the passive
stabilization model as one possible answer to
this mystery. His premise is a simple one –
because each DA neuron both releases and
uptakes dopamine, the loss of each DA neuron
represents not only the loss of dopamine
molecules being released but also one less
neuron taking up dopamine molecules. Of
course, every hypothesis must be supported by
research. Enter the neuro lab and see for
yourself if Dr. Garris’ hypothesis is supported or
refuted.
Research in Parkinson’s Disease
• Students are instructed to go to the
______ room and do the experiment found
in the protocol.
• INSERT LAB HERE
• Do we want students to create a
hypothesis or choose a hypothesis going
into the experiment?
Looking at the Lab Data
Dopamine Release
Dopamine Uptake
90
80
70
60
50
Dopamine Release
40
30
20
10
0
0
10
20
30
40
50
60
70
Percentage of DA neurons
80
90
Percentage of Dopamine Uptake
Percentage of Dopamine Release
100
100
90
80
70
60
50
Dopamine Uptake
40
30
20
10
0
0
10
20
30
40
50
60
70
80
90
Percentage of Dopamine Neurons
The data from the experiment indicate that the as the number of
dopamine neurons decreases, so does the uptake and release of
dopamine.
Is Garris’ passive stabilization hypothesis supported by
this data? Explain your answer.
How can dopamine tone remain stable as dopamine
release decreases?
Leaving the lab
• Student is instructed to then leave the lab
and return to the Parkison’s Disease
tutorial.
The Bucket Theory
• While Garris’ passive stabilization
hypothesis is supported by the data, why
dopamine tone suddenly drops after the
loss of about 80% of an individual’s
dopamine neurons. In order to help
explain this phenomenon, Garris created
the Bucket Theory.
• Student is instructed to do activities.
The Bucket Theory Activity 1
• Examine the Bucket Theory animation
below and …(need to determine what
students should do here)
• One thing that the original Bucket Theory
didn’t seem to quite explain was why the
20% DA neuron threshold was so
important. Dr. Garris hypothesized that
there must be something else affecting the
DA tone.
The Bucket Theory Activity 2
• Look at the DA neuron synapse and hypothesize
as to what else might be affecting DA tone.
• Glial cells take up minimal amounts of dopamine
and, when there is a sufficient concentration of
DA neurons, the glial cells do not seem to affect
DA tone. However, at a DA neuron concentration
of less than 20%, the uptake of DA by the glial
cells seems to have a much greater impact on
the DA tone. This line of thought led to a
revamping of the Bucket Theory.
The Bucket Theory Activity 3
• Examine the revised Bucket Theory
animation below and…(need to determine
what students should do here)
• Another way to look at the passive
stabilization model is through computer
modeling. Watch the video below to
become familiar with the computer model.
The Bucket Theory Activity 4
• Explore the computer model of the passive
stabilization theory.
• Need to figure out activity/questions