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The Physiological Components of Parkinson’s Disease

Kaylee Blankenship

Human Physiology 60

Kathi Joye

March 30, 2011

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The Physiological Components of Parkinson’s 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 Parkinson’s disease (PD). Until recent

years Parkinson’s 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 Parkinson’s disease is a rapid neurodegenerative disorder that has serious

negative symptoms and a complex physiology.

As previously stated, Parkinson’s 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 Parkinson’s, 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 Parkinson’s 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 (“Parkinson’s

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 (“Parkinson’s

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

(“Parkinson’s 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 (“Parkinson’s 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 Parkinson’s disease

(“Parkinson’s 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 (“Parkinson’s Disease”).

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There have been many studies conducted regarding the way the brain’s

functions change as Parkinson’s 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 Parkinson’s (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 Parkinson’s (Baglio et al). There are also studies

that are trying to find links between Parkinson’s 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 Parkinson’s, 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 Parkinson’s, 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

Parkinson’s Disease,” broadcasts some of those side effects. Studies have found that

though the disease responds well to the dopamine precursor levdopa and its agonist’s

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 Parkinson’s 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.