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Pathophysiology of Parkinson's Disease

Two hypotheses are referred to as the mechanisms of neuronal degeneration in Parkinson's disease are: the free radical hypothesis and the hypothesis neurotoxins.
1. Free radical hypothesis. Alleged that the enzymatic oxidation of dopamine can damage neurons nigrotriatal, because this process produces hidrogren peroxide and other oxygen radicals. Although there is a protective mechanism to prevent damage from oxidative stress, but at the advanced age of this mechanism may fail.
2. Allegedly neurotoxin hypothesis of one or more kinds of neurotoxic substances play a role in the process of neurodegeneration in Parkinson's disease.
Current view, emphasizing the importance of the basal ganglia in neurophysiology plan required in performing the movement, and the part played by the cerebellum is to evaluate the information received as feedback on the implementation of the movement. Basal ganglia primary task is to collect the program for the movement, while the cerebellum monitor and rectification of errors that occur during movement of the program is implemented. One sign of extrapyramidal disorder is involuntary movement. Basic pathology included lesions in the basal ganglia (caudate, putamen, palidum, subtalamus nucleus) and brainstem (substantia nigra, nucleus rubra, locus ceruleus). Simply put, motor system disease or disorder can be divided as follows:
1.Piramidal; paralysis accompanied by an increased tendon reflexes and superficial reflexes are abnormal
2. Extrapyramidal: dominated by the presence of involuntary movements
3. Cerebellar: normal propioseptif ataxia or sensation often accompanied by nystagmus
4. Neuromuscular: paralysis is often accompanied by muscle atrophy and reduced tendon reflexes. Pathophysiology of depression in Parkinson's disease until now has not known for sure. But this theoretical allegedly associated with deficiency of serotonin, nor-adrenaline and  dopamine. Degenerate in Parkinson's disease neuronal cells that includes a variety of subcortical nuclei including the substantia nigra, ventral tegmental area, nucleus basalis, hypothalamus, pedunkulus Pontin, the dorsal raphe nucleus, locus cereleus, nucleuscentral pontine and autonomic ganglia. Severity of damage to this structure varies. At autopsy found loss of substantia nigra cells and cereleus locus varies between 50% - 85%, whereas in the dorsal raphe nucleus ranged between 0% - 45%, and the nucleus of the basal ganglia between 32% - 87%. Subcortical nuclei are a major source of neurotransmitters.. Involvement of this structure result in reduced dopamine in the caudate nucleus (reduced to 75%), putamen (reduced to 90%), hypothalamus (reduced to 90%). Norepinephrine was reduced 43% in the locus sereleus, 52% in the substantia nigra, 68% in the posterior hypothalamus. Serotonin is reduced 40% in the caudate nucleus and hippocampus, 40% in the frontal lobes and 30% in the temporal lobes, and 50% in the basal ganglia. There was also a reduction in specific nuropeptid such as Met-enkephalin, leu-enkephalin, substance P and bombesin. Changes lead to changes in neurotransmitters and neuropeptid neurofisiologic associated with changes in the atmosphere of feeling. Transmitter systems involved in this process mediates reward, motivation mechanisms, and response to stress. Dopamine system plays a role in the process of reward and reinforcement.
There was a doctor named Febiger, he put forward the hypothesis that abnormalities in neurotransmitter systems in Parkinson's disease will reduce the effectiveness of the mechanism of reward and lead to anhedonia, loss of motivation and apathy. Meanwhile, another doctor called, he emphasized the importance of the role of forebrain dopamine systems in the behavioral functions of hope and anticipation. This system plays a role in motivation and encouragement to do, so this dysfunction will lead to excessive dependence on the environment by reducing the desire to do the activity, decreased sense of ability to control themselves. Decreased ability to control feelings can manifest themselves as feeling useless and lost self-esteem. Dependence on the environment and the inability to perform the activity will lead to feelings of helplessness and despair. Serotonergic system plays a role in the regulation of mood feelings, waking regulation, aggression and sexual activity. Dysfunction of this system will cause disruption in sleep patterns, loss of appetite, decreased libido, and decreased ability to concentrate. Merging dysfunction all the elements mentioned above is the picture of classic depression syndrome.


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