Parkinson's Disease: Unraveling the Mystery

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Parkinson's Disease: Unraveling the Mystery Parkinson's disease, which affects over one million Americans, results in the progressive loss of coordination, unstable posture, and tremor (1). In 1817, James Parkinson, after whom the disease was named, was the first to document cases of what he called "the shaking palsy" and in doing so, began the scientific crusade to determine the causes and manifestation of the disease (2). The challenge before neuroscientists was to determine the link between Parkinson's behavior and alterations of the nervous system. This task would be accomplished by employing a system of working backwards - - first determining the gross problem and then attempting to understand it at a neuronal level. The first step in linking changes in the brain to Parkinson's behavior occurred in the early 1900's with autopsies performed on people who suffered from the disease (2). Such procedures revealed significant cell death in the midbrain - - more specifically of pigmented cells that are collectively known as the substantia nigra ("black substance," named for the presence of melanin). Because damage to the substantia nigra resulted in impaired motor control, it was logically hypothesized that this area played a role in the control of movement. With the knowledge that neurotransmitters were the means of communication for the nervous system, autopsy testing in the 1950's of Parkinson's patients showed that dopamine levels in an area adjacent to the substantia nigra, known as the striatum, were only about 10-20% of the levels present in unaffected individuals (3). The parallel of the low level of dopamine and the death of cells of the substantia nigra in Parkinson's patients led scientists to postulate that the substantia nigra produces dopamine. When levels were disrupted due to cell death, this would likely lead to a change in stimulation in this area of the brain, which would produce behavior characteristic of Parkinson's. Anatomical research since then has shown that the substantia nigra is part of the basal ganglia, whose other components include the globus pallidus, subthalamic nucleus, and striatum (3). Through experimentation, a series of nerve signal pathways have been mapped out which help us to understand how this region of the brain functions to control movement. It has been hypothesized that cells of the frontal cortex initiate signals for movement (4). (It was concluded that the basal ganglia does not initiate movement because damage to this area as occurs in Parkinson's still allows for voluntary movement; if it were responsible for its initiation, the damage would likely inhibit voluntary movement.

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