Biology - Down's Syndrome - Term Paper Example

? Down’s Syndrome TEACHER               Down’s Syndrome Introduction According to the National Institutes of Health, Down syndrome is “the most common single cause of human birth defects” (Kaneshiro, 2010). Down syndrome is a trisomy of chromosome 21, which means that there are three chromosomes for pair 21 and so the person has a total of 47 chromosomes. With its horrible mental and physical symptoms, Down syndrome is certainly a huge concern not only for medical professionals and for medical science but especially for the parents of those affected with this deadly and incurable genetic disorder. Nevertheless, despite the alleged incurable nature of Down’s syndrome, it is possible that the fields of pharmacology and medicine have surely come up with ways to alleviate its symptoms as well as to be able to learn further about the disease. In fact, research through the medical and scientific databases on the latest scientific breakthroughs concerning Down’s syndrome resulted in the discovery of five journal articles relating the most recent breakthroughs on the disease. Review of Literature The study of Bradeau et al. conducted in Paris, France in 2011 is entitled “Specific targeting of the GABA-A receptor ?5 subtype by a selective inverse agonist restores cognitive deficits in Down syndrome mice.” Based on the results of this study, one reason why there is an altered brain function among individuals with Down’s syndrome is that there is a chemical imbalance between inhibitory and excitatory neurotransmitters. One inhibitory transmitter, GABA or gamma-aminobutyric acid seems to occur in large amounts in the nervous system of Down’s syndrome patients and thus causes a relatively great amount of inhibition of certain cognitive functions among them. The study then utilized GABA-A antagonists in order to treat such chemical imbalance and the result was positive. As a result, the subjects of the experiment, Ts65Dn mice, or mice with Down’s syndrome, demonstrated restored cognitive functions. The specific chemical GABA-A antagonist, which is a ?5-subtype or ?5IA, was used to restore memory and learning functions n rats. The ?5IA subtype of GABA-A antagonist is different from its other subtypes because it is non-convulsant, which means to say that the other subtypes may cause convulsions if tested on humans. Other subtypes also caused certain changes in the tissues of the brain, liver and kidney of the experimental mice, but ?5IA did not. The study of Braudeau et al. was particularly important to the medical community as well as to families of Down’s syndrome patients because this new particular chemical or drug – GABA-A antagonist ?5IA subtype – may actually improve learning and memory problems among patients suffering from Down’s syndrome. Nonetheless, the drug has not yet been tested in humans for fear that although it may not cause convulsions in rats, it may still do so in humans. Moreover, the study was unique in itself because although it has been known that Down’s syndrome patients suffer from imbalanced inhibition and excitation at the cellular level, there had been no non-convulsant drug that promised any good cure until now. Another study, the one conducted by Perluigi and Butterfield in Kentucky, USA in 2011 is entitled “Oxidative Stress and Down Syndrome: A Route toward Alzheimer-Like Dementia.” This study involved the discovery of the physiological causes of the almost natural development of Alzheimer’s Disease among Down’s syndrome patients as early as their middle age. Although there are already genetic physical and mental abnormalities in a newborn child with Down’s syndrome, these pathological problems get worse as the patient gets older and thus may have a great chance of developing into Alzheimer’s Disease later on in life. The study found out that the causes of such development were “altered free radical metabolism” and “impaired mitochondrial function” (Perluigi & Butterfield, 2012). These two cellular processes, which contribute greatly to the degeneration of neurons, affected cells that showed evidence of oxidative stress, according to the research study of Perluigi and Butterfield. The study was unique in the sense that the approach was purely theoretical and no actual experiment was conducted. Older studies were simply analyzed and compared with existing literature on oxidation, free radicals and mitochondrial function and dysfunction. Through the study of various past clinical trials, the authors were able to come up with a conclusion that defined the significance of the study. The authors concluded that the link between Down’s syndrome and Alzheimer’s disease can be explained by the impaired mitochondria and free radicals in the neurons. The link can be explained as well by the cellular pathways that these factors undergo as they gradually lead to the oxidative stress that actually triggers the occurrence of Alzheimer’s disease. A third study, the one conducted by Nelson et al. at the University of California- Los Angeles in 2011 is entitled “Positron Emission Tomography of Brain ?-Amyloid and Tau Levels in Adults With Down Syndrome.” The study was conducted in order to determine the “neuropathological load” or the extent of damage of brains of adults with Down’s syndrome. What was used to determine this was positron emission tomography using a chemical known as [18F]FDDNP in order to find out the extent and location of neuronal damage among Down’s syndrome patients as their ages progress and as their behaviors change pathologically. For the purpose of comparison, a control group and a group of Alzheimer’s disease patients were also used as subjects for the experiment. The results revealed that Down’s syndrome patients had more pronounced damage in the parietal and frontal lobes. Age also revealed an increasing damage in neurons in almost all regions of the brain. Lastly, behavioral dysfunction also revealed damage in all areas of the brain and an increase in the extent of affected parts meant a corresponding increase in the intensity of the behavioral dysfunction. The study by Nelson et al. was unique because it was one of the first studies of its kind to measure the extent of brain damage among Down’s syndrome patients as well as the location of the affected areas of the brain. It also tried to check whether increasing age and increasing behavioral dysfunction meant an increase in the extent of damage, and it turned out the hypotheses were true. The results of the study are significant to the medical community as well as to parents with children affected with Down’s syndrome because now the brain is mapped according to how Down’s syndrome progresses in the individual. When a particular area of the brain is expected to be affected with neuronal damage at a certain time in the future, then at least the particular type of physiological damage and its corresponding physical symptoms may be foreseen. Thus, parents can be more prepared and medical professionals would know what to expect and would at least be able to apply necessary measures to mitigate the symptoms. Another study on Down’s syndrome was the one conducted by Tenenbaum et al. in Israel in 2011. It is entitled “Anemia in Children with Down Syndrome.” This was not an experimental study but rather one which used children in a Down’s syndrome medical center as subjects and their blood, nutritional history, medical history and physical development were taken into consideration. Using 140 children as subjects, it was found out that 8.1% had anemia and 50.0% had iron deficiency. Moreover, Arab ethnicity and low weight were significant factors for the occurrence of anemia, and that height, gender, the presence of a congenital heart disease and an eating disorder are not factors for anemia in Down’s syndrome patients. The study was unique in that it was not experimental in nature and it tried to link nutrition and Down’s syndrome. It also tried to find whether there was a significant link between anemia and Down’s syndrome. The results implied the significance of the study. The idea that Down’s syndrome patients had 50.0% iron deficiency somehow implies that anemia and Down’s syndrome may be significantly correlated. This has two corresponding implications. First, parents of children with Down’s syndrome can at least prepare to counter anemia in their children by giving them proper nutrition. Another implication would be that Down’s syndrome and the complications that go with it may cause significant changes in the blood itself, in the production of blood in the bone marrow, or in the ability of the blood to conduct oxygen. A fifth study, the one conducted by Perluigi et al. in Rome, Italy in 2011, is actually entitled “Oxidative stress occurs early in Down syndrome pregnancy: A redox proteomics analysis of amniotic fluid.” The study was about trying to determine if the fetus in the pregnant woman’s uterus is already affected by Down’s syndrome or the oxidative stress that goes with the disease. The results revealed an increasing amount of oxidative stress and other proteins that were common only to fetuses with Down’s syndrome. These proteins included those that were known to be involved in iron homeostasis, lipid metabolism, and inflammation. These proteins are oxidized in fetuses with Down’s syndrome. This means that these proteins may not be able to function well in a patient with Down’s syndrome, and that if one is suffering from this particular genetic disorder, it is expected that his utilization of iron and fat is inefficient and that the inflammation of his external and internal organs may usually occur. This may also explain the fat deposits, and cases of anemia and unusual inflammation that may occur in patients with Down’s syndrome. The study was unique in a sense that data from pregnant women were used to come up with the results of the study. The study was also important and significant to all those afflicted with Down’s syndrome especially the women pregnant with affected babies because they can at least determine in advance whether the baby is sick with Down’s syndrome or not. Moreover, the results of the study at least make the medical professionals as well as parents of affected children will become more aware in advance of the threats of anemia, fat and inflammation that may affect their children. Graphs/Data One particular cause of Down’s syndrome is the age of the mother when giving birth. Specifically, this means that as the mother’s age increases, the incidence of Down’s syndrome in her child also increases as well. Here is data from the National Down’s Syndrome Society: Incidences and Maternal Age Maternal Age Incidence of Down syndrome Maternal Age Incidence of Down syndrome 20 1 in 2000 35 1 in 350 21 1 in 1700 36 1 in 300 22 1 in 1500 37 1 in 250 23 1 in 1400 38 1 in 200 24 1 in 1300 39 1 in 150 25 1 in 1200 40 1 in 100 26 1 in 1100 41 1 in 80 27 1 in 1050 42 1 in 70 28 1 in 1000 43 1 in 50 29 1 in 950 44 1 in 40 30 1 in 900 45 1 in 30 31 1 in 800 46 1 in 25 32 1 in 720 47 1 in 20 33 1 in 600 48 1 in 15 34 1 in 450 49 1 in 10 Source: http://www.ndss.org/index.php?option=com_content&view=article&id=61&Itemid=78 Here are latest available data on the occurrence of Down’s syndrome in the United States: Source: CDC, http://www.cdc.gov/features/dsdownsyndrome/ Source: CDC, http://www.cdc.gov/features/dsdownsyndrome/ Conclusion Based on the results of the five studies above, there have been several recent significant breakthroughs when it comes to the diagnosis and treatment of Down’s syndrome. Nevertheless, much future research has to be done regarding the disease. The results of the study by Braudeau et al. revealed a challenge for medical science to test GABA-A ?5IA subtype antagonist on humans. However, much research and experimentation must be done first before this is done because GABA-A may act as a convulsant in humans and may cause irreparable damage in the patient. The second study, the one by Perluigi & Butterfield, challenges scientists and medical professionals to conduct in-depth research studies and experiments on the exact mechanisms that the impaired mitochondria and free radicals undergo in order to manifest Alzheimer’s disease in a Down’s syndrome patient. If these mechanisms are determined, they can be stopped or blocked and thus Alzheimer’s disease may be prevented. The third study, the one by Nelson et al., is actually a call for more research studies and experiments regarding the more specific parts of the brain that are affected by Down’s syndrome. If the all the parts of the brain damaged by the disease are mapped, then there is a good chance that remedies can be prepared beforehand. Moreover, a more in-depth understanding of the relationship between Down’s syndrome and affected location of the brain may lead scientists understand more how the disease progresses and therefore learn how to anticipate it and find ways to stop it. The fourth study, the one by Tenenbaum et al., implies that there must be a significant connection between Down’s syndrome and the human circulatory system or simply the human blood. Discovering this link may be the key to preventing anemia that accompanies Down’s syndrome. Lastly, the fifth study, the one by Perluigi et al., supposes that Down’s syndrome may in fact be diagnosed even in the fetal stage, and that adequate knowledge of the affected proteins in the fetus may be the key to preventing Down’s syndrome even in the womb or at least reducing its symptoms before the baby is born. Bibliography Braudeau J, Delatour B, Duchon A, Lopes Pereira P, Dauphinot L, de Chaumont F, Olivo-Marin JC, Dodd RH, Herault Y & Potier MC. (2011). “Specific targeting of the GABA-A receptor ?5 subtype by a selective inverse agonist restores cognitive deficits in Down syndrome mice.” Journal of Psychopharmacology, 25(8), 1030-1042. Retrieved Feb. 17, 2012 from the National Institutes of Health: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3160204/. Kaneshiro NK. (2010). Down syndrome. Retrieved Feb. 16, 2012 from the National Institutes of Health: http://www.nlm.nih.gov/medlineplus/ency/article/000997.htm. Nelson LD, Siddarth P, Kepe V, Scheibel KE, Huang SC, Barrio JR & Small GW. (2011). “Positron Emission Tomography of Brain ?-Amyloid and Tau Levels in Adults With Down Syndrome.” Archives of Neurology, 66(6). Retrieved Feb. 18, 2012 from the Arc of California: http://thearcca.org/reports/Nelson%20et%20al%202011.pdf. Perluigi M & Butterfield DA. (2012). “Oxidative Stress and Down Syndrome: A Route toward Alzheimer-Like Dementia.” Current Gerontology and Geriatrics Research. Retrieved Feb. 12, 2012 from Hindawi.com: http://www.sciencedirect.com/science/article/pii/S1383571810001968. Perluigi M, di Domenico F, Fiorini A, Cocciolo A, Giorgi A, Foppoli C, Butterfield DA, Giorlandine M, Giorlandino D, Schinina ME & Coccia R. (2011). “Oxidative Stress occurs early in Down syndrome pregnancy: A redox proteomics analysis of amniotic fluid.” Proteomics Clinical Journal, 5, 167-178. Retrieved Feb. 16, 2012 from the University of Kentucky: http://as-houston.ad.uky.edu/archive/as17/as17.as.uky.edu/academics/departments_programs/Chemistry/Chemistry/FACULTYRESEARCH/FACULTY/DAllanButterfield/Documents/Perluigi%20et%20al%202011%20Proteomics%20-%20Clinical%20Applications%205%20167-178.pdf. Tenenbaum A, Malkiel S, Wexler ID, Levy-Khademi F, Revel-Vilk S & Stepensky P. (2011). “Anemia in Children with Down Syndrome.” International Journal of Pediatrics. Retrieved Feb. 17, 2012 from Hindawi.com: http://downloads.hindawi.com/journals/ijped/2011/813541.pdf. Read More