Effect Disorders Have on Adult Neurogenesis - Research Paper Example

Effect Disorders Have on Adult Neurogenesis Introduction Neurogenesis has been linked with hippocampal-dependent functions such as the learning and memorization of explicit information as well as emotional response. Most factors that have a positive influence on the proper functioning of the hippocampus such as treatment of depression by antidepressants and having an enriched environment, have been known to increase neurogenesis. On the other hand, factors that negatively interfere with the proper functioning of the hippocampus such as depression, and diseases such as Alzheimer and schizophrenia, have been purported to reduce neurogenesis. Therefore, neurogenesis normally leads to production of new neuronal cells that serves to provide an additional stock of plasticity to allow the adult brain to adapt to changing environmental cues. This in the end provides the possibility of making stable modifications between the existing neuronal network and its cognitive and emotional functions. Winer, Kohl and Hage present that the generation as well as cell death of a cell of a newly generated tissue, plays a significant role in the development and maintenance of the brain of both adults and embryos. Consequently, any alterations in such processes are normally seen in the presence of a neurodegenerative disease. There are a number of such diseases that that tend to interfere with the proper functioning of the brain and other associated neurological functions. These diseases include Alzheimer’s disease, Schizophrenia, Epilepsy and Depression. This paper seeks to analyze the various effects of that these disorders have on adult neurology. Moreover, the precise effect of each of these disorders will also be highlighted with particular interest on the specific part of the brain the disorders tend to affect. Discussion According to Scharfman, in the adult brain neurogenesis usually occurs in three distinct areas, the subventricular zone, the olfactory bulb and the dentate gyrus of the hippocampus. Winer, Kohl and Gage document that disorders that tend to interfere with the proper neurological functioning of the adult brain, are associated with certain genes that play a great part in the development of the disorders. Some of these genes include presenilin, and alpha-synuclein. They tend to have some psychological effect in the modulation of the plasticity of the brain especially on protein membranes and areas with a high concentration of synapses. Additionally, the alpha-synuclein gene also tend to interfere with the synthesis of dopamine, whose synthesis, metabolism, subsequent release or slight change in concentration may have profound effects on the release of the neurotransmitter. Neurodegenerative disorders have a high inclination of sharing certain common characteristics such as the induction of progressive loss of structure or the functions of neurons, glial cells of the brain as well as the spinal cord. Moreover, these disorders also share a common characteristic such as the initiation of assemblies of proteins and subsequent oligomerization and consequently cell death. In adults, Winer, Kohl and Gage, posit that adult neurogenesis normally increases following several acute pathologic stimuli such as seizures, stroke or acute trauma. These disorders initiate a chronic yet slow progressive process. In turn, the neurons are then affected by neuronal dysfunction at the synaptic transmission level, synaptic junctions as well as axonal and dendritic degeneration. In the event that the disorders lead to chronic neurodegeneration, much impact is felt on the stem cells maintenance, survival and the general functional integration of the cells. Winer, Kohl and Gage present that the pathology of Alzheimer’s disease generally entails the loss of neurons and synapse function. This mostly occurs due to the deposition of Amyloid Beta proteins in the basal forebrain choligernic neurons and in the hippocampus, cortex as well as amygdale. Alzheimer’s disease is a neurodegenerative disease that is characterized by amyloid plaque deposits and neurofibrillary tangles in the brain. It is regarded as one of the most common form of dementia in elderly people. According to Mathew, recent evidence shows that neurogenesis tends to occur in the adult brain and neural stem cells lie in the adult central nervous system. Leoni indicates that the toxic effect of Alzheimer’s disease is as a result of Amyloid beta oligomeric species. This is evidenced by the correlation of memory lose and oligomerization in both mice and adult humans. On the other hand, Leoni points out that AD begins with abnormal processing of an amyloid precursor protein that leads to either excessive production or reduced clearance of amyloid beta oligomers in the brain. Such elevated amounts of the amyloid beta oligomers leads to the formation of plaques that in turn contribute to a cascade characterized by abnormal aggregation, synaptic dysfunction, brain atrophy, shrinkage and eventually cell death. In Alzheimer’s disease, a common patient experiences a decline in cognitive functioning, memory impairment and eventually death. According to Wine, Kohl and Wage, genetic studies have pointed out some early-onset and autosomal dominant mutations for Alzheimer’s disease. According Taupin, Alzheimer’s disease is associated with the loss of nerve cells in areas of the brain that play a vital role in memory as well as other mental abilities such as the hippocampus. This implies that major disabilities of Alzheimer’s disease are mainly cognitive impairments that tend to worsen with time. Taupin presents that in 2004; Jin conducted an autopsy of the brain of an AD patient that revealed that the most affected part of the brain was the subgranular zone of the dentate gyrus and a CA1 hippocampal region. The subgranular is a layer that lies beneath the granular layer. It is from this region that newly formed neurons migrate into the granular layer prior to differentiation in mature neuronal cells. According to Taupin, genetic studies have revealed early –onset and autosomal dominant mutations for Alzheimer’s disease. This in turn interferes with the expression of different mutant genes including those that encode Amyloid precursor proteins as well as Presenilin. On the other hand, epilepsy is among the oldest and perhaps the most well known brain disorder. One common type of epilepsy is the Temporal Lobe Epilepsy (TLE). Just like the name implies, TLE is mainly characterized by termporary seizures that normally originate from the temporal lobe region. Research indicates that the disorder is induced by an infection of the central nervous system, especially by either meningitis or encephalitis. In most instances, the disorder usually remains dormant for a long period only to manifest itself later in adulthood and is normally exhibited by the reoccurrence of temporary seizures whose origin has been traced to the hippocampus. Scharfman presents that epileptic seizures are among the most vigorous stimuli that tend to increase neurogenesis in a normal adult brain. Epilepsy tends to have an immense effect on adult neurogenesis especially in the dentate gyrus of the hippocampus, being a brain part that is particularly susceptible to seizures. Sharfman further illustrates that the granule cell, the major dentate gyrus cell type, is the primary type of cell that is usually born in the adult dentate gyrus. These granule cells tend to be highly affected with epilepsy. Scharfman reveals that epileptic seizures may induce neurogenesis in adults by a number of factors such as an increase in the neuronal activity or brain injury. This implies that seizures that lead to very little or no damage, such as kindle seizures, can increase neurogenesis. She also indicates that based on the fact that seizures and injuries increase neurogenesis and have the potential to induce various growth factors, like peptides, that stimulate neurogenesis, epilepsy can sometime contribute to neurogenesis indirectly. Seizures have also been known to enhance neuronal activity, which may stimulate neurogenesis by direct synaptic activation of some precursor cells that receive synaptic contacts. Sharfman presents that there are a number of factors that promote neurogenesis, among them is neural activity. In this regard, Sharfman is of the opinion that seizures may also increase neurogenesis especially in the dentate gyrus since it boosts neuronal activity. He further presents a study that indicates that when adult male rats or mice were injected with a seizure-induced agent, kainic acid, intratcerebroventricularly, the results revealed that neuregenesis considerably decreased within the injected area but increased in the contralateral hippocampus. On the same point, Scharfman presents that the pro-epileptic role of seizure–induced neurogenesis is supported by findings that granular neurons formed some weeks before or after an epileptogenesis-triggering incident, are normally typified by uncharacteristic appearances and location as well. These newly formed neurons were established to contribute to the recurrent excitatory circuit within the epileptic dentate gyrus, suggesting that there is a strong link between epileptogenesis and neurogenesis. Similarly, the effect of experimentally induced seizures on adult neurogenesis investigated using the BrdU labeling technique reported a marked increase in dentate granule cell neurogenesis following seizure activity in the pilocarpine model. Trembley supports this idea and reports that in epilepsy, neurogenesis is enhanced in the brain following limbic-induced seizures and newly generated cells in the dentate gyrus contribute to hippocampal plasticity associated with seizures. On the contrary, in events of chronic seizures, neurogenesis tends to decrease due to the depletion of the precursor cells that are involved in the Notch signaling pathway that either differentiate or proliferate thus inducing neurogenesis, or remain undifferentiated to inhibit neurogenesis. Thus, this implies that the decline in neurogenesis during the chronic phase in Temporal Lobe Epilepsy is due to impairment in determination of the fate of a cell rather than a decrease in the number of progenitor cells. Just like in the case of epilepsy, the hippocampus is one of the brain structures that have been extensively studied with regard to the consequences of stress, depression, and antidepressant actions. According to Porter, studies in humans revealed that the hippocampus undergoes selective volume reduction in stress-related neuropsychiatric disorders such as recurrent depressive illness. He further explains that depression is associated with a reduced level of endogenous neurogenesis. This is due to the fact that increased depression increases the production of cortisol that in turn stimulates excessive release of glutamine in the extracellular space, which rescues the survival of new neurons in the dentate gyrus in the event of stress. According to Samuels, stress due to depression has indeed been thought to precipitate and worsen major depressive disorders as well as a decrease in cell proliferation within the SGZ and hippocampal neurogenesis as demonstrated through the exposure of various animals to various stressors. Moreover, the effects of depression on neurogenesis or cell proliferation have been found both after acute and chronic stress. This has been established based on several models that have been employed that induce a suppressive effect on hippocampal neurogenesis such as restraint stress and unpredictable chronic mild stress. The inhibition of neurogenesis by depression can also be illustrated by the fact that positive effects of antidepressants have been accompanied by an increase in hippocampal neurogenesis. This implies depression and neurogenesis work antagonistically to each other. Trembley documents that schizophrenia tends to disturb the organization of pyramidal cells in the hippocampus. This consequently leads to a reduction in the tissue volume of both the hippocampus and the amygdale. Samuels asserts that depression hormones lead to reduced hippocampal volume and decrease the rate of neurogenesis in the dentate gyrus, by decreasing cell proliferation and survival of newly formed cells. On the other hand, antidepressants also play a role in increasing the rate of neurogenesis thereby serving to protect an organism from adverse effects of stress. The most likely means by which depression may suppress adult neurogenesis in the hippocampus is regarded to be through activation of the hypothalamic-pituitary–adrenal axis and subsequent elevation of levels of cortisol. Schizophrenia is regarded as the most chronic and disabling severe mental disorder. The origin and mechanism of the schizophrenia are not well understood. However, it is mostly considered as a developmental disorder that results from impaired migration of neurons in the brain during fetal development, or from non-genetic factors such as environmental stress during fetal development or at birth. Samuels presents that neurogenesis is enhanced in the dentate gyrus of a rat with ketamine-induced schizophrenia. Owing to the fact that schizophrenia is usually expressed in the hippocampus, it may have diverse functions in neuronal migration and differentiation and synaptic plasticity, similarly, it controls the integration of new neurons in the course of adult hippocampal neurogenesis. According to Strart, Ramoz and Gorwood, the effect of Alzheimer’s disease and schizophrenia on neurogenesis can be distinguished from each other based on the fact that in schizophrenia, there is no clear evidence of the common characteristics of neurodegeneration. Unlike Alzheimer’s disease, Schizophrenic cases do not normally involve the build of plaques or neurofibrillary tangles. Therefore, this implies that unlike Alzheimer, schizophrenia is not regarded as a neurodegenerative disease. They further state that in the presence of the disease, there is usually a high inclination of the formation of oligodendrocytes, which together with the glia, serve to support as well as protect and revitalize the surrounding neurons and synapses. Thus, it is evident that this is an initiation of neurogenesis in the SVZ and the hippocampus. They further present that in the lifetime of a schizophrenic case, the hippocampus tends to maintain a high standard of neural plasticity. Therefore, a reduction in the glial mass may lead to a decrease of nuerogenesis in schizophrenia. Moreover, Strart, Ramoz and Gorwood document that in schizophrenia, adult neurogenesis and neuroplasticity could be involved in various temporal phases, which in turn would help in various cognitive alteration related to the disease. These functions are associated with the prefrontal and hippocampal regions, which are some of the most highly neuroplastic regions of the neural system. Conclusion One common aspect of all these neurological disorders emanates from the fact that neurogenesis is enhanced in the hippocampus and SVZ. Most animal models used in the explanation of the effect of depression on neurogenesis have revealed that neurogenesis in the dentate gyrus and cell proliferation do not necessary correlate with depressive-like behavior, instead, they correlate with factors that modulate behavior such as stress and antidepressants. As also seen, neurodegenerative diseases comprise a wide range of diseases that share the common characteristic of progressive loss of structure or function of neurons and glial cells in the brain and spinal cord. Many of these diseases are as a result of neuronal loss. Diseases such as the Alzheimer’s disease tend to lead to loss of neurons through protein assemblies and oligomerization as well as induction of cell death. Works cited Porter, Brenda E. "Neurogenesis and Epilepsy in the Developing Brain." Epilepsia, 2008: 50-54. Print Samuels, Benjamin A. "Neurogenesis and affective disorders." European Journal of Neuroscience, 2011: 1151-1159. Print Strat, L, Y Ramoz, and P Gorwood. "The role of genes involved in neuroplasticity and neurogenesis in the observation of a gene-environment interaction (GxE) in schizophrenia." Research Support, 2009: 506-518.Print Scharfman1, Helen E. "Seizure-Induced Neurogenesis in the Dentate Gyrus and its Dependence on Growth Factors and Cytokines." Growth Factors and Epilepsy, 2006: 1-40.Print Taupin, Philippe. "Neurogenesis and Alzheimer’s Disease." Drug Insight, 2006: 1-4.Print Tremblay, Matthew. "Epilepsy and Neurogenesis." Fall, 2003: 20-26. Print Winer Beate, Zacharias Kohl, and Fred Gage. "Neurodegenerative disease and adult neurogenesis." European Journal of Neuroscience, 2011: 1139-1151.Print Read More