Basic neurobiology of Parkinson's disease - final project for Coursera course - Understanding the Brain: The Neurobiology of Everyday Life by Peggy Mason.

1. Understanding the Brain: The
Neurobiology of Everyday Life
Final Project
Parkinson’s Disease
by Rachael Shaw

2. What is Parkinson’s Disease
Described by James Parkinson in 1817 Parkinson’s is characterized by degeneration of central
nervous tissues, affecting the motor skills of a person, thereby impairing movements and speech.
Parkinson’s disease is a degenerative neurological disease affecting more men than women with
no known cure, Parkinson’s (or idiopathic parkinsonism) has no identifiable cause. It is
distinguished from secondary parkinsonism, a group of disorders similar to Parkinson’s that have
known or identifiable causes.
Most people are diagnosed between 60 and 70 years old, however some people are diagnosed
with early Parkinson’s such as actor Michael J. Fox at age 30.

3. Symptoms
In most people Parkinson’s first noticeable
effects are related to movement, people may
have a resting tremor(s), rigidity, balance
issues, bradykinesia (slowing or loss of
spontaneous/automatic movement) and/or
akinesia (difficulty in initiating voluntary
movements).
Some known early symptoms are rarely
recognised due to their slow and gradual
onset, these include expressionless face,
cramped handwriting, slight shakiness and
mild cognitive impairment in executive
functions (eg planning, decision making and
emotional control). Other early symptoms
may not be seen as related to Parkinson’s for
example loss of ability to sing.
Image 1

4. As Parkinson’s progresses other effects such as impaired cardiovascular regulation,
dizziness, changes in blood pressure, digestive disorders, constipation, urinary
urgency and urinary incontinence can occur.
As well as physical effects Parkinson’s can also affect thought, emotions, sleep and
memory.
In later stages hallucinations and dementia can occur.

5. What causes Parkinson’s symptoms?
What is known is Parkinson’s first noticeable
symptoms are caused by cell death in the
substantia nigra (part of the basal ganglia).
Dopamine is produced in the substantia
nigra, cell death reduces the production of
dopamine and subsequently the release of
dopamine from neurons is reduced.
The substantia nigra is darkly pigmented in a
normal brain, as can be seen in image 1 the
substantia nigra is brownish black. In a
Parkinson’s patient, the substantia nigra is
barely distinguishable from the surrounding
area’s indicating there are few dopamine
producing cells.
Image 2
Currently the cause of Parkinson’s is unknown.

6. When approximately 60 to 80% of dopamine is
lost, symptoms such as tremor, slowness of
movement, stiffness, and balance problems
occur.
It is usually when one or more of these
symptoms are evident a diagnosis of Parkinson’s
can be made (once any other neurological issue
or disease has been excluded).Image 3
A recent hypothesis in Parkinson’s research is that two parts of the brain are
involved in Parkinson’s. The substantia nigra is affected first and as Parkinson’s
progresses the basal forebrain (involved in memory and attention) is affected in a
similar way.
A smaller basal forebrain is believed to reduce the production of acetylcholine,
(neurotransmitter with decreased concentration and function in Alzheimer's
disease). This may be a partial cause of dementia and/or memory isssues in some
Parkinson’s patients.

7. The Brains Dopamine System
The dopamine system is controlled by two
area’s the substantia nigra and the ventral
tegmental area (vtc). The vtc also produces
dopamine and releases it into the frontal lobe.
The vtc dopamine pathway may also play a role
in Parkinson’s.
The substantia nigra manufacture and releases
dopamine into the striatum. Dopamine reduces
the influence of the indirect pathway, and
increases the actions of the direct pathway
within the basal ganglia and plays a critical role
in controlling movement. A reduction in
dopamine levels has a direct effect on a
persons ability to execute smooth, controlled
movements and on the indirect and direct
pathways.
Image 4

8. In Parkinson’s reduced dopamine
production and release result in dopamine
receptors in the striatum being
inadequately stimulated. When this occurs
parts of the basal ganglia are under- or
over-stimulated.
Issues with motion and rigidity are the
result of the subthalamic nucleus becoming
overactive and acting as a brake on the
globus pallidus interna.
Tremors are caused when the globus
pallidus interna is overstimulated resulting
in an over-inhibitory effect on the
thalamus, which in turn decreases the
thalamus’ output. See the optional video
Parkinson's Disease and Dopamine showing
this process.
Brain Regions Affected
Image 5

9. Optional videos
http://www.youtube.com/watch?v=BarcIuIEsKk
http://www.youtube.com/watch?v=la63uShbtsc
CNN Special: Full interview with Michael J. Fox as he talks
to Dr. Sanjay Gupta about Parkinson's disease and The
Michael J. Fox Foundation. 40.02 minutes
Diane Sawyer's Exclusive Interview With Linda
Ronstadt
Rock star discusses her secret battle that silenced her
singing voice.
4.27 minutes
Parkinson's Disease and Dopamine
The process resulting in a tremor in a series of animations.
1.22 minutes.
http://www.youtube.com/watch?v=jyBakRkzswU

10. Image credits
Image 1 http://careplannursing.blogspot.com.au/2012/03/parkinsons-disease-nursing-care-plan.html
Image 2 http://www.nlm.nih.gov/medlineplus/ency/imagepages/19515.htm
Image 3 http://www.anti-agingfirewalls.com/2012/06/30/a-stem-cell-cure-for-parkinsons-disease-so-close-
and-yet-so-far-away/
Image 4 http://thesalience.wordpress.com/neuroscience/neurotransmitters/
Image 5 http://www.parkinsondisease.in/

11. Bibliography
http://www.nytimes.com/2012/11/27/health/imaging-shows-progressive-damage-by-parkinsons.html?_r=0
Imaging Shows Progressive Damage by Parkinson’s, James Gorman, November 26, 2012 New York Times
http://online.wsj.com/news/articles/SB10001424052748703748904575411662795000790
How Parkinson's Alters the Brain - Researchers Trace Clues to the Disease's Effects on Patients' Mental Ability, Shirley
S. Wang Aug. 10, 2010 Wall Street Journal
http://www.medicalnewstoday.com/info/parkinsons-disease/
All About Parkinson’s Disease
http://biomed.brown.edu/Courses/BI108/BI108_1999_Groups/Neuroelectrodes_Team/background.html
Background of Parkinson's Disease
http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001762/
Parkinson's disease Paralysis agitans; Shaking palsy
http://www.parkinson.org/parkinson-s-disease.aspx
https://www.michaeljfox.org/understanding-parkinsons/index.html
http://www.parkinsons.org.au/about-ps/whatps.html

12. How this course allowed me to better
analyse events and phenomena around
me.
This course gave me the opportunity to learn and understand basic
Neurobiology and neurobiological terms I have previously come across. I have
been fascinated by the brain for a long time and have been unable to study in a
traditional way. Thanks to courses like this one I can learn more than I ever
could reading scientific journals and other materials.
I now feel able to apply knowledge from the course and better understand how
my brain may be functioning or malfunctioning, particularly in relation to my
sleep issues and the remnant effects of many years of drug and alcohol
dependence/abuse. I have also gained a better understanding of my Dad’s
Parkinson’s disease and my friends ongoing battle with anxiety and depression.
This course has given me a much greater appreciation of the complexity of the
brain and the many issues that can arise when the brain incurs damage or
there is a malfunction. Thanks Dr. Peggy Mason and the staff at Coursera!