Brain mechanisms underlying Parkinson disease - Essay Example

? Brain mechanisms underlying Parkinson disease Introduction Parkinson’s disease (PD) is a slowly occurring, neurodegenerative disease. It occurs as a result of degeneration of neurons within the substantia nigra, which is a region of the brain responsible for controlling movements. Degeneration of neurons leads to the shortage of dopamine, which controls body movements. With a reduction in the production of dopamine, the body suffers from impaired movements. Symptoms associated with PD start to show up later in life when a person attains the age of 40 years and over. Primary Parkinsonism and idiopathic Parkinson’s disease are terms used to distinguish PD from other forms of Parkinsonism (Pfeiffer et al 2012, p. 285). Discussion Being a chronic neurodegenerative disease, there are four main motor manifestations that characterize this medical condition. These cardinal signs are tremor at rest, bradykinesia, rigidity, and postural instability. It is worth noting that the four cardinal signs of PD may not be present in all patients, but patients show at least two of the cardinal signs. The initial complaint from patients with PD is that of motor weakness; in most cases, there is a misdiagnosis on the cause of this sign. Later during the course of disease progression, signs of tremor and postural deficits may appear, prompting physicians to reconsider the cause of the signs (Pfeiffer et al 2012, p.291). Diagnosis of PD is based on neurological examinations and patient’s medical history, but there is a diagnostic test that can help in the identification of PD. Tremor at rest, being a common sign in about 70% of patients suffering from PD, is not used in PD's diagnostic procedure. This is because there are other neurological conditions that present with signs similar to those of Parkinsonism. However, rigidity helps physicians during the diagnosis of PD since it is associated with resistance in limb movements. On the other hand, bradykinesia is associated with slowness and paucity of movement. Bradykinesia may affect the oropharynx, which causes difficulties in swallowing. Postural instability is the most life threatening cardinal sign due to its potential to cause falls that can lead to serious body fractures (Beal et al 2005, p.358). Pathophysiology (brain mechanism in PD) PD is a complex neurodegenerative disease that affects body movements as the medical condition progresses. Apart from interferences with body movements, PD produces a wide range of medical complications on the affected patient. Symptoms of PD vary among patients affected by the condition. When they occur, they may include difficulties in swallowing, excessive sweating, depression, variation in emotions, and urinary complications. The severity of symptoms associated with PD vary among patients, but none of the symptoms is life threatening. Difficulties in swallowing can cause chocking. Progression of these symptoms can take up to 20 years although the condition progresses much quickly (Halliday et al. 2010, p.54). As mentioned earlier, substantia nigra is the primary brain region, which is affected by PD. This part of the brain houses the dopaminergic neurons, which generate signals that travel to the striatum through the axons (Dawson 2007, p.17). The role of signals generated by the dopaminergic neurons is to regulate normal body movements. Loss of dopaminergic neurons causes a shortage of dopamine, which leads to excessive firing of cells of the striatum. The excessive firing of these neurons makes patients suffering from PD unable to control their body movements, which marks the beginning of initial signs of PD. As the disease progresses, majority of patients with PD usually lose over 80% of dopamine producing cells (Santens et al 2003, p.130). Continued research on brain mechanism during PD has identified a number of cellular characteristics present in PD, which are believed to contribute immensely in the degeneration neurons. The most common characteristic present in neurons found in the substantia nigra, and other brain regions are the presence of Lewy bodies (Santens et al 2003, p.136). Lewy bodies This are aggregates of proteins occurring in neurons of patients affected by PD. Close examination of lewy bodies reveals the presence of an eosinophilic core surrounded by a pale halo (Dawson 2007, p.30). Eosinophilic cores are usually round, but their shape may be pleomorphic at times. These inclusions are commonly observed within the cell soma, but they can also occur in the extracellular space or neuritis. Lewy bodies occur commonly in regions of the brain that have suffered the greatest loss of neurons due to PD. Regions where lewy bodies are most common include locus coeruleus, SN, and the nucleus basalis of Meynert. They can also be observed in the spinal cord, diencephalon, neocortex, and the peripheral, autonomic ganglia (Santens et al 2003, p.141). Lewy bodies have an electron dense granular core as well as a peripheral halo. In addition, lewy bodies have another antigenic feature, which is the expression of cellular proteins responsible for the degeneration of proteins. These antigenic cellular proteins include ubiquitin and proteasome. The overall effect of the presence of lewy bodies in neurons is the interference with the process of transmitting nerve signals plus other essential neuronal functions (Beal et al 2005, p.378). Neuron loss Loss of neurons of the substantia nigra is the hallmark pathologic feature in PD. At the terminal stage of PD, even mildly affected patients show up to 60% loss of their DA neurons. The 60% loss in neurons plus the dysfunctional neurons constitute 80% loss of neurons within the corpus striatum. Continued degeneration of DA terminals leads to a reduction in DA uptake. These changes and other inherent changes in DA terminals and DA receptors allow for the continuation of striatal functions without disruption in early stages of neural degeneration. Occurrence of larger lesions causes the remaining DA terminals to increase the production of the transmitter as well as the delivery of transmitters to the extracellular fluid (Edwards et al. 2008, p.121). Initial changes in neuronal functions are thought to be due to a net increase in the production of DA in response to terminal depolarization. These changes are a consequence of defects in homeostatic regulatory systems present within the affected systems. After the release of DA, some components of this neurotransmitter diffuse out of the synapse into the extracellular space. Once in the extracellular space, the action of DA is prolonged due to the absence of sites that are of high affinity DA uptake. These events are believed to allow SNpc to continue having a dopaminergic control on striatal cells, which is possible in situations where there are minimum numbers of DA terminals. On the other hand, an increase in the synthesis and release of DA can lead to an increase in the level of reactive metabolites arising from DA, which contribute to the progression of PD (Edwards et al. 2008, p.125). There are several groups of dopaminergic neurons within the central nervous system, but the loss of DA neurons within the SNpc is believed to cause the motor manifestation observed in PD. This clinical manifestation is supported by the fact that N-methyl- 4-phenyl-1, 2,3,6-tetrahydropyridine acts selectively to DA neurons within SNpc and at the same time can produce the whole spectrum of motor signs observed in PD. In addition, not all of the DA neurons present in the SNpc that are involved in the progression of PD. In PD, the ventral, lateral region appears to be the most severely affected compared to the dorsal region. However, central dopaminergic systems, which include the hypothalamic systems and the ventral tegmental region, are less affected during PD (Edwards et al. 2008, p.126). The descending spinal dopaminergic systems remain totally unaffected by changes that occur in PD. The other essential thing to note is that loss of neurons during PD not only occurs on dopaminergic neurons, but also occurs on other types of neurons. Examples of other affected neurons during PD include serotonergic neurons, neurons of the sympathoadrenal system, and catecholaminergic cells. Loss of cholinergic neurons also occurs during PD affecting the nucleus basalis of Meynert (Halliday et al. 2010, p.72). References List Beal, F., Lang, A. & Ludolph, E. (2005). Neurodegenerative Diseases: Neurobiology, Pathogenesis and Therapeutics, Cambridge, Cambridge University Press. pp. 358-400. Dawson, T. M. (2007). Parkinson's Disease: Genetics And Pathogenesis, New York, Taylor & Francis Group. pp. 17-30. Edwards,M., Quinn, N., Edwards, M. & Bhatia, K. (2008). Parkinson's Disease and Other Movement Disorders, Oxford, Oxford University Press. pp. 120-127. Halliday,G.Barker, R.& Rowe, P. (2010). Non-dopamine Lesions in Parkinson's Disease, Oxford, Oxford University Press. 54-72. Pfeiffer, R., Wszolek, M. & Ebadi, Z. (2012). Parkinson's Disease, Second Edition, New York, CRC Press. pp. 284-295. Santens, P., Boon, P., Roost, V. & Caemaert, J. (2003). The pathophysiology of motor symptoms in Parkinson’s disease. Acta neurol. belg103. pp.129-134. Read More