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The Physiological Components of Parkinsons Disease

Kaylee Blankenship
Human Physiology 60
Kathi Joye
March 30, 2011

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The Physiological Components of Parkinsons Disease

What if you lost the ability to control your body, whether it be moving you legs or
back or even talking? Though this may seem like an impossibility to some, it is a definite
and unfortunate reality for people who have Parkinsons disease (PD). Until recent
years Parkinsons disease was not very well known; however, now because of
individuals such as Michael J. Fox and Muhammad Ali, there has become a serious
focus on creating an awareness of the disease in addition to increased research of
causes and possible treatments. In consequence of this research, many possible
clinical trials and treatments have emerged, but so far it is obvious that there is still a
long ways to go before a truly effective treatment can emerge. All that is known for sure
is that Parkinsons disease is a rapid neurodegenerative disorder that has serious
negative symptoms and a complex physiology.
As previously stated, Parkinsons is a neurodegenerative disorder that eventually
results in tremors and difficulty with coordination and movement. This disease has been
directly linked to the inhibition of the release of the hormone dopamine and the
disappearance of dopaminergic pigmented neurons in the substantia nigra. PD is also
connected to the presence of Lewy Bodies which are concentric, eosinophilic,
cytoplasmic inclusions with peripheral halos and dense cores (Hauser et al). Though
there has been a correlation made between these bodies and Parkinsons, their
presence in the body does not automatically mean that the individual has the disease,
because they can also be found in the cerebral cortex, locus ceruleus, column of the
spinal cord, and other areas. However, the presence of Lewy bodies is currently
hypothesized to correspond with a presymptomatic phase of PD. In accordance with

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recent studies, it was found that the effects of Lewy bodies begin in the olfactory bulbs
and the brain stem which in turn causes rapid eye movement in addition to a loss of
smell when in the early phases of the disease (Hauser et al). The path of the bodies
starts going up of brain stem and then, eventually gets to the midbrain and nigrostriatal
dopaminergic neurons later on. This spreading is what eventually causes the
degradation of the motor systems characteristic of Parkinsons disease.
Basal ganglia in the Cortical-Basal Ganglia Loop are essential factors in the
movement of the body, therefore, with the onset of PD comes the destruction of these
pathways. The nuclei include the caudate nucleus, putamen, and the globus pallidus,
from which inputs from the cerebral cortex are received. The pathology and the location
of the nuclei create a loop where the basal ganglia receive information about planned
movements which are then performed by the primary motor cortex (Parkinsons
Disease). It all starts when inputs from the primary motor cortex and the primary
somatosensory cortex of the brain are sent to the the putamen. The signal is then sent
to the caudate and, after, to globus pallidis which has two outputs. The first is the motor
nuclei of the brain stem and the other is the subthalamic nucleus (Parkinsons
Disease). From there the signal travels to the motor cortex by way of the ventrolateral
thalamus and the loop is finally complete when information from the primary motor and
primary somatosensory cortex is sent to the putamen, shown below.

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The loop is also maintained by two neurotransmitters, identified as glutamate and

GABA. The area of the substantia nigra sends excitatory and inhibitory signals to the
caudate by the use of dopamine, which then innervates multiple putamen areas
(Parkinsons Disease). The inhibitory signal is taken into the putamen, and it is then
relayed to the external globus pallidus developing an IPSP. The inhibition then creates
an EPSP at the internal globus pallidus, creating an inhibitory signal that is then sent to
the thalamus producing an EPSP (Parkinsons Disease). The final excitatory message
is passed along to the motor cortex, finally producing a motor response. On the other
hand, the excitatory input from the substantia nigra has basically the same pathway.
Like the inhibitory pathway, an IPSP is produced at the internal globus pallidus. After
that, the pathway is the same as the aforesaid. Therefore, the basic overall effect of the
loop is excitatory; however, with the decrease in dopamine production, the pathway is
inhibited causing the characteristic motor movement impairment of Parkinsons disease
(Parkinsons Disease). In other words, the normal excitatory request that is sent to the
motor cortex is instead inhibitory. The picture below is a visual representation of the
cortical-basal loop (Parkinsons Disease).

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There have been many studies conducted regarding the way the brains
functions change as Parkinsons disease progresses. One such study has tried to
determine whether or not abnormalities of the frontostriato-thalamic network can be
detected in those patients in the early stages of Parkinsons (Baglio et al). As shown by
the cortical-basal loop, the basal ganglia play a huge role in processing information
about motor response throughout the body. The study found that an fMRI has the ability
to provide specific information about the pathology and physiology of the brain which
allowed for researchers to prove their hypothesis. In the end, they found that patients
with early PD can present early symptoms in the brain, which can help with future trials
as well as figuring out the history of Parkinsons (Baglio et al). There are also studies
that are trying to find links between Parkinsons and genes. The discovery of genes
carrying mutations aids in identifying those biochemical pathways that mediate the
disease process. There has, however, been differing evidence as to what the model of
familial PD targets, including, mitochondria, dopaminergic neurotransmission, and
autophagy or lysosomes (Wolozin et al). Though some evidence has been acquired,
there are still no positive answers. LRRK2 mutations are what are the most frequently

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identified genetic changes in Parkinsons, however, researchers are still not quite sure
as to how it contributes to PD pathology.
In recent years, researchers have been looking at many different forms of
treatment for Parkinsons, but with these new drug treatments there are bound to be
some side effects along the way since the area of research is so new. A report from
Alain Dagher and Trevor W. Robbins, Personality, Addiction, Dopamine: Insights from
Parkinsons Disease, broadcasts some of those side effects. Studies have found that
though the disease responds well to the dopamine precursor levdopa and its agonists
ropinirole and pramipexole, side effects of these medications have been increasingly
reported instances of personality changes in addition to numerous types of addictions
(Dagher and Robbins). Some individuals have developed addictions to the medication,
gambling, shopping, and just compulsive and behavioral addictions in general.
Dopamine acts on cortico-striatal neurons which are what typically influence addiction
and disorders of decision making, motivation, and learning. In psychology it is known as
reward learning and reinforcement, of which dopamine is the mechanism. Within
separate studies it was found that none of the patients treated with levodopa alone
reported gambling, but a significant percentage did develop the problem within at least a
month of an increase of a dopamine agonist dose (Dagher and Robbins). So, parallels
are being drawn between dopamine and developing the hypothesis that novelty
seeking is related to an elevated dopamine response to some sort of rewarding stimuli,
such as gambling or shopping. With fMRIs and other neuroimaging, this correlation was
able to be confirmed. Dopamine acts on cognitive, sensorimotor, and limbic regions of
the striatum, of which the ventral striatum receives input from limbic areas which

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typically correspond with drug addiction. This helps to draw the conclusion that extreme
limbic dopaminergic stimulations are implicated in the impulse control disorders (Dagher
and Robbins).
It is clear that discoveries in the area of Parkinsons research still have quite a
long ways to go, but, so far, much of its physiology is identified. PD is a severely
neurodegenerative disorder of which dopamine plays an integral part. The complex
physiology an pathology of the disease also does not help with finding a cure. The
medications that are being used now will also have to be modified as studies continue.
Though some studies have shown onset of addiction from these medications, it only
shows that science takes years and years of investigation and research to perfect.

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Works Cited
Baglio, F., V. Blasi, A. Falini, E. Farina, F. Mantovani, F. Olivotto, G. Scotti, R. Nemni,
and M. Bozzali. "Functional Brain Changes in Early Parkinson's Disease during
Motor Response and Motor Inhibition." Neurobiology of Aging (2009): 115-24.
Print.
Dagher, Alain, and Trevor W. Robbins. "Personality, Addiction, Dopamine: Insights from
Parkinson's Disease." Neuron 61.4 (2009): 502-10. Print.
Hauser, MD, MBA, Robert A., Rajesh Pahwa, MD, Kelly E. Lyons, PhD, and Theresa
McClain, MSN, ARNP. "Parkinson Disease." Emedicine. 18 Oct. 2010. Web. 24
Mar. 2011.
<http://emedicine.medscape.com/article/1151267-overview>.
Macalester. "Parkinson's Disease." Macalester College: Private Liberal Arts College.
Web. 29 Mar. 2011.
<http://www.macalester.edu/psychology/whathap/UBNRP/parkinsons/webpage.h
tml>.

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Wolozin, Benjamin, Shamol Saha, Maria Guillily, Andrew Ferree, and Misha Riley.
"Investigating Convergent Actions of Genes Linked to Familial Parkinson's
Disease." Neurodegenerative Diseases (2008): 182-85. Print.