Effects of Acetylcholinesterase Inhibitors on Delay Induced Deficits in the Novel Object Recognition - Literature review Example

?Alzheimer's disease Alzheimer's disease Introduction Alzheimer’s disease is a disease, which has no cure and eventually leadsto death. The brain disorder is mostly related to old age and many people believe that the disease is resulting from stress. The disease is sporadic and hence not inherited (Szekely CA, 2007). It is not a genetic disease. However, it is mostly associated with autosomal inheritance especially those that are not sex linked. Mutations in the brain proteins are a contributing factor to the cause of this disease. The mutations alter the arrangement of the protein folding hence leading to malfunctioning. Despite the early symptoms and manifestation of the diseases being similar to stress, the disease is not emanating from stress. Some of the symptoms of the disease include memory loss during the early stages. Execution of movements also starts to change and is affected at the start of the disease. Older memories are not affected so much but the newly learnt memory is what is affected at the early stages of the disease (Wozniak M, 2008). As the disease is progressing people affected with the disease will most of the time require assistances since they are unable to execute most the duties independently. As the disease advances and enters into a moderate state, most people are unable to speak well. Patients suffering from the disease also encounter difficulties of paraphrasing words since confusion about vocabularies develop. Dissolution begins and loss of insights creep in s the disease advances. At certain conditions, urinary incontinence may develop. Due to this condition, most caretakers are advised to reduce tension and stress on the patient’s side. Change of environment from one place to another also helps in improving the status of the caretakers and the patients. The patients totally depending on their caretakers characterize the advanced stage of the disease. There is also complete loss of speech while understanding and communicating begins to be a total failure for these patients. Performance of simple tasks such as eating also fail and the muscles weakens completely (McLean SL, 2008). Pathophysiology The disease occurs due to the missfolding of proteins in the brain. The proteins in question include amyloid beta and amyloid tau (Wendler A, 2012). The plaques that affect the brain are made up of 39-43 amino acids, which are small peptides from beta amyloid. Beta amyloid is a precursor of a larger protein in the brain by the name trans membrane protein. The membranous protein has the ability of penetrating through the neurons. The membrane plays a significant role in the survival and growth of neurons. It helps in protecting neurons, survival and helps in post injury repair of neurons. For the case of Alzheimer’s disease, the membrane is affected and it breaks down into small fragments, which affects the neurons. These effects can be translated to loss of memory and inability to carry out certain tasks mainly due to inactive neurons. The breakdown or the fragmentation of these protein leads to formation of the plaques known as senile plaques. The protein tau becomes affected by undergoing chemical changes. Tau protein has the function of protecting microtubules that holds the fibrils of the axon an important component of the neuron. When the neurons are broken down into smaller fragments they are incapacitated hence cannot send various messages to the brain (McLean SL W. M., 2009). The subcortical regions in the brain are the major area that is affected by Alzheimer's disease. The cerebral cortex is affected when the neurons and the synapse fail to work and are completely lost. The effect of this loss results in gross atrophy in the regions that have been affected. This disease also affects the temporal lobe in addition to parietal lobe. The left sphere of the brain is also affected especially the cingulate gyrus. The frontal cortex of the brain are amongst the important regions that are affected by these disease. Scans by analysts and doctors reveals a decreased size and shape of the brain for people affected with the disease (Charles, 2008). This comparison is related to people with similar age but not differing from the disease. Plaques such as amyloid and neurofrilliary tangles can be observed through a microscope for patients suffering from this disease. The plaques mostly surround the neurons. The cells in the other hand are affected by neurofribrillary tangles which accumulate inside the cells. Although development of plaque is synonymous with the old people, but for people suffering from this diseases the effects are more severe. The effects are more visible and present in the temporal lobe of the brain. Treatment The disease can be diagnosed by collecting the patients history. Neurological and neuropsychological features can also help he doctor in trying to treat this disease. Medical scanning at advanced level an also be used to identify the disease. Computed tomography and magnetic resonance imaging are among the various ways that doctors use in diagnosing the disease. The doctor can identify the stage of the disease by conducting intellectual functioning tests on the patient. The doctor following criteria and asking several questions easily does this. The test also involves physical activities that help in diagnosing the disease. In addition to testing the memory, the criteria also tests the remaining 7 domains that include language, skills, attention, orientation, problem solving, functional abilities, and perceptual skills (JT, 2007). Pharmaceutical management Currently there are 5 drugs that are used in treating the manifestations of AD. The drugs include donepzil, galantamine, rivastigmine, and tacrine. These four drugs are acetylcholinsterase inhibitors (McLean SL N. J., 2010). The other drug memantine is a receptor antagonist. Research indicates and proves that none of these drugs has the ability to delay or halt in any way the progress of the disease. Just as the name suggest, acetylcholinsterase inhibitors work by reducing the rate at which acetylcholine breaks down. When rate of breakdown is reduced, acetylcholine concentration in the rain increases and this helps in reducing the rate at which neurons perish since it helps in nourishing the neurons with nutrients and necessary energy to perform their functions. Donepezil is the only drug permitted for treatment of advanced stage of AD (McLean SL G. B., 2011). The others are used for treatment at moderate and early stages. However, the drugs have side effects on the patients. The side effects include vomiting and nausea, which doctors believe, is due to cholinergic excess production. Muscle crumps, loss of appetite, weight loss, and increased gastric acid production are amongst some side effects, which may be experienced at low levels. Memantine drug is an antagonist. It works by acting as a no competitive receptor antagonist by acting on glutamatergic system, which is useful in production of glutamate. Glutamate is used in exciting neurotransmitters of the nervous system. According to analysts and most researchers, excessive production of glutamate leads to the death of cells in the brain. This happens when the cells become so much exited (Rabinovici GD, 2009). By moderating the level of glutamate in the brain helps in reducing the numbers of cells dying thereby improving the functioning of the brain cells and the nervous system. Memantine is used in treating mild and moderate stages of the disease. The effects of this drug at the initial stage is unknown. Just like many other drugs, this drug has side effects such as hallucinations confusion, dizinness, cases of fatigue, and headaches. Analyst suggests the combination of Memantine and Donepezil results in significant management of the disease (McLean SL N. J., Effects of asenapine, olanzapine, and risperidone on psychotomimetic-induced reversal-learning deficits in the rat, 2010). Under certain conditions, use of antipsychotic drugs is recommended especially if he patient is aggressive and suffering from control of behavior. However, these drugs are not administered mostly due to their grave side effects on the patients such as reduced movements and cognitive decline. Novel Object Recognition Test Novel object Recognition test evaluates the cognitive development of a the memory. This test is widely applied to rodents suffering from CNS disorders. The scientific theme behind this model is the ability of a rodent to widely focus on a novel object than familiar objects. This helps the researcher to identify whether learning and development is taking place. (Marksteiner J, 2007). The test is normally done at an open field where to objects are placed. The objects should differ in shape and size but it is recommended that they are similar in height. The exercise is conducted with first introducing the rodent to the empty field. After 24 hours the familiar object are introduced to the rodent. The next 24 hours the rodents are then exposed to both familiar and novel objects. The test is then examined based on the time taken to observe the novel object. This helps in exploring the long-term memory of the rodent. Bibliography Charles, H. (2008). Methylthioninium Chloride (MTC) Acts as a Tau Aggregation Inhibitor (TAI) in a Cellular Model and Reverses Tau Pathology in Transgenic Mouse Models of Alzheimer's Disease. Alzheimer's & Dementia, 4(4):T120–T121. . JT, O. (2007). Role of Imaging Techniques in the Diagnosis of Dementia. Br J Radiol, 80(Spec No 2):S71–7. Marksteiner J, H. H. (2007). Cerebrospinal Fluid Biomarkers for Diagnosis of Alzheimer's Disease: Beta-amyloid(1–42), Tau, Phospho-tau-181 and Total Protein. Drugs Today, 43(6):423–31. McLean SL, B. J. (2008). A preliminary investigation into the effects of antipsychotics on sub-chronic phencyclidine-induced deficits in attentional set-shifting in female rats. Behavioural Brain Research, 189: 152-158. McLean SL, G. B. (2011). Activation of ?7 nicotinic receptors improves phencyclidine-induced deficits in cognitive tasks in rats: implications for therapy for cognitive dysfunction in schizophrenia. European Neuropsychopharmacology, 21: 333-343. McLean SL, N. J. (2010). Effects of asenapine, olanzapine, and risperidone on psychotomimetic-induced reversal-learning deficits in the rat. Behavioural Brain Research, 214: 240-247. McLean SL, N. J. (2010). Effects of asenapine, olanzapine, and risperidone on psychotomimetic-induced reversal-learning deficits in the rat. Behavioural Brain Research, 214: 240-247. McLean SL, W. M. (2009). D1-like receptor activation improves PCP-induced cognitive deficits in animal models: implications for mechanisms of improved cognitive function in schizophrenia. European Neuropsychopharmacology, 19: 440-450. Rabinovici GD, J. W. (2009). Amyloid Imaging in Aging and Dementia: Testing the Amyloid Hypotheses in Vivo. Behav Neurol, 2009;21(1):117–28. Szekely CA, T. T. (2007). NSAIDs for the Chemoprevention of Alzheimer's Disease. Subcell Biochem, 42:229–48. Wendler A, W. M. (2012). Translatability scoring in drug development: eight case studies. Journal of Translational Medicine , 10 (10): 39. Wozniak M, M. A. (2008). Herpes Simplex Virus type 1 DNA Is Located within Alzheimer's Disease Amyloid Plaques. J Pathol, 217(1):131–138. Read More