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- Creators: School of Molecular Sciences
- Creators: Sanabria, Federico
Description
As the incidence of dementia continues to rise, the need for an effective and non-invasive method of intervention has become increasingly imperative. Music therapy has exhibited these qualities in addition to relatively low implementation costs, therefore establishing itself as a promising means of therapeutic intervention. In this review, current research was investigated in order to determine its effectiveness and uncover the neurochemical mechanisms that lead to positive manifestations such as improved memory recall, increased social affiliation, increased motivation, and decreased anxiety. Music therapy has been found to improve several aspects of memory recall. One proposed mechanism involves temporal entrainment, during which the melodic structures present in music provide a framework for chunking information. Although entrainment's role in the treatment of motor defects has been thoroughly studied, its role in treating cognitive disorders is still relatively new. Musicians have also been shown to demonstrate extensive plastic changes; therefore, it is hypothesized that non-musicians may also glean some benefits from engaging in music. Social affiliation has been found to increase due to increases in endogenous oxytocin. Oxytocin has also been shown to strengthen hippocampal spike transmission, a promising outcome for Alzheimer's patients. An increase in motivation has also been found to occur due to music's ability to tap into the reward center of the brain. Dopaminergic transmission between the VTA, NAc and higher functioning regions such as the OFC and hypothalamus has been revealed. Additionally, relaxing music decreases stress levels and modifies associated autonomic processes, i.e. heart rate, blood pressure, and respiratory rate. On the contrary, stimulating music has been found to initiate sympathetic nervous system activity. This is thought to occur by either a reflexive brainstem response or stimulus interpretation by the amygdala.
ContributorsFlores, Catalina Nicole (Author) / Redding, Kevin (Thesis director) / Hoffer, Julie (Committee member) / Neisewander, Janet (Committee member) / School of Molecular Sciences (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Immediate early genes (IEGs) are rapidly activated in response to an environmental stimulus, and most code for transcription factors that mediate processes of synaptic plasticity, learning, and memory. EGR3, an immediate early gene transcription factor, is a mediator of biological processes that are disrupted in patients with schizophrenia (SCZ). A microarray experiment conducted by our lab revealed that Egr3 also regulates genes involved in DNA damage response. A recent study revealed that physiological neuronal activity results in the formation of DNA double-stranded breaks (DSBs) in the promoters of IEGs. Additionally, they showed that these DSBs are essential for inducing the expression of IEGs, and failure to repair these DSBs results in the persistent expression of IEGs. We hypothesize that Egr3 plays a role in repairing activity- induced DNA DSBs, and mice lacking Egr3 should have an abnormal accumulation of these DSBs. Before proceeding with that experiment, we conducted a preliminary investigation to determine if electroconvulsive stimulation (ECS) is a reliable method of inducing activity- dependent DNA damage, and to measure this DNA damage in three subregions of the hippocampus: CA1, CA3, and dentate gyrus (DG). We asked the question, are levels of DNA DSBs different between these hippocampal subregions in animals at baseline and following electroconvulsive stimulation (ECS)? To answer this question, we quantified γ-H2AX, a biomarker of DNA DSBs, in the hippocampal subregions of wildtype mice. Due to technical errors and small sample size, we were unable to substantiate our preliminary findings. Despite these shortcomings, our experimental design can be modified in future studies that investigate the role of Egr3 in activity-induced DNA damage repair.
ContributorsKhoshaba, Rami Samuel (Author) / Newbern, Jason (Thesis director) / Gallitano, Amelia (Committee member) / Marballi, Ketan (Committee member) / School of Molecular Sciences (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
Chronic stress is a risk factor for many diseases that impact the brain, including Alzheimer’s Disease. Unlike acute stress, chronic stress reduces neuronal plasticity, which can lead to neuronal remodeling and suppression. This project investigates the effect of stress on the dendritic complexity of hippocampal neurons in rats, demonstrating a methodology for procuring and analyzing these neurons. The brains of the 160 rats from the Sustained Threat and Timing (STAT) experiment were frozen. The STAT experiment investigated the effect chronic variable stress had on prospective and retrospective timing in rodents. Using a cryostat, thin coronal slices of brain tissue were placed on microscopic slides. The tissue samples were then stained using the Golgi method of silver staining. Hippocampal neurons were assessed using Sholl Analysis; the dendritic complexity of these neurons was quantified. The method of using Sholl Analysis was found to be an effective process in measuring dendritic length of hippocampal neurons.
ContributorsMiller, Amara Delaney (Author) / Sanabria, Federico (Thesis director) / Gupta, Tanya (Committee member) / School of Life Sciences (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
Stress activates physiological systems within the body to protect oneself against the potential harmful effects of enduring long-term stress. Past studies have shown that structures involved in timing are implicated in a number of psychological disorders and further are sensitive to stress. In this experiment, Sprague Dawley rats are trained to perform a perspective timing task and are then exposed to twice-daily chronic variable stress for 21 days. Behavioral data are collected, followed by post-mortem tissue analysis of the PFC, hippocampus, and striatum. This study aims to examine the morphological changes in key brain regions such as the hippocampus that appear to be involved in interval timing. Additionally, this study aims to confirm that dendritic complexity in the hippocampus produces consistent data using a classic Sholl analysis versus using a virtual image-stacking software, Neurostackr. The results of this study demonstrate that the expected Gaussian graph produced from a classic Sholl analysis was produced from both a long-shaft and short-shaft neuron found in the hippocampus using the virtual technology. These findings verify that a virtual image-stacking software and Sholl analysis will suffice in place of the traditional method of hand traced neurons on a transparent sheet with concentric circles to count bifurcation points. This virtual method ultimately reduces cost, improves timeliness of data collection, and eliminates some of the subjectivity of human error.
ContributorsGarcia, Jasmine Brooke (Author) / Sanabria, Federico (Thesis director) / Gupta, Tanya (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
The mammalian target of rapamycin (mTOR) is integral in regulating cell growth as it maintains a homeostatic balance of proteins by modulating their synthesis and degradation. In the brain, mTOR regulates protein-driven neuroplastic changes that modulate learning and memory. Nevertheless, upregulation of mTOR can cause detrimental effect in spatial memory and synaptic plasticity. The proline-rich Akt-substrate 40 kDa (PRAS40) is a key negative regulator of mTOR, as it binds mTOR and directly reduces its activity. To investigate the role of PRAS40 on learning and memory, we generated a transgenic mouse model in which we used the tetracycline-off system to regulate the expression of PRAS40 specifically in neurons of the hippocampus. After induction, we found that mice overexpressing PRAS40 performed better than control mice in the Morris Water Maze behavioral test. We further show that the improvement in memory was associated with a decrease in mTOR signaling, an increase in dendritic spines in hippocampal pyramidal neurons, and an increase in the levels of brain-derived neurotrophic factor (BDNF), a neurotrophin necessary for learning and memory. This is the first evidence that shows that increasing PRAS40 in the mouse brain enhances learning and memory deficits.
ContributorsSarette, Patrick William (Author) / Oddo, Salvatore (Thesis director) / Caccamo, Antonella (Committee member) / Kelleher, Raymond (Committee member) / School of Molecular Sciences (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Okur-Chung Neurodevelopmental syndrome (OCNDS) is a rare disorder characterized by hypotonia, developmental delay, dysmorphic features, and more. It is caused by pathogenic variants on CSNK2A1, the α subunit of protein kinase CK2. CK2 is considered a master regulator involved in many cell functions from cell differentiation and proliferation to apoptosis. Here, we create a potential zebrafish model of OCNDS with CK2 inhibition and characterize fibroblast cells with, K198R, D156E, and R47G variants of CSNK2A1. RNAseq results display a wide range of effects notably in the Myosin Protein superfamily, Insulin-like Growth Factor family, and in proteins related to mitochondrial function and cell metabolism. Factors in cell growth and metabolism across the nervous system and neuromuscular interactions appear to be most affected with similarities in markers to oncogenic states in some cases.
ContributorsLeka, Kamawela (Author) / Newbern, Jason (Thesis director) / Rangasamy, Sampath (Committee member) / Barrett, The Honors College (Contributor) / School of Molecular Sciences (Contributor) / Harrington Bioengineering Program (Contributor)
Created2023-05
Description
Mammalian olfaction relies on active sniffing, which both shapes and is shaped by olfactory stimuli. Habituation to repeated exposure of an olfactory stimuli is believed to be mediated by decreased sniffing; however, this decrease may be reserved by exposure to novel odorants. Because of this, it may be possible to use sniffing itself as a measure of novelty, and thus as a measure of odorant similarity. Thus, I investigated the use of sniffing to measure habituation, cross-habituation, and odorant similarity. During habituation experiments, increases in sniff rate seen in response to odorant presentation decreased in magnitude between the first and second presentations, suggesting of habituation. Some of this reduction in sniff rate increases was revered by the presentation of a novel odorant in cross-habituations. However the effect sizes in cross-habituation experiments were low, and the variability high, forestalling the conclusion that sniffing accurately measured cross-habituation. I discuss improvements to the experimental protocol that may allow for cross-habituation to be more accurately measured using sniffing alone in future experiments.
ContributorsVigayavel, Nirmal (Author) / Smith, Brian (Thesis director) / Sanabria, Federico (Committee member) / Gerkin, Rick (Committee member) / Barrett, The Honors College (Contributor)
Created2015-12
Description
The primary channel responsible for cold thermo-transduction in mammals is the transient receptor potential melastatin 8 (TRPM8) channel. TRPM8 is a polymodal, nonselective cation channel with an activation that is dependent on a variety of signals, including the membrane potential, calcium concentration, temperature, and ligands such as menthol. Mathematical modeling provides valuable insight into biochemical phenomena, such as the activity of these channels, which are difficult to observe experimentally. Here, we propose a TRPM8 gating model, represented as a system of ordinary differential equations with menthol, calcium, voltage, and temperature dependencies. We use voltage-clamp data from transfected HEK293 cells in the presence of menthol to create a menthol-dependent voltage shift of activation. We fit the parameters of the TRPM8 gating model to replicate experimental TRPM8 transfected HEK293 cell voltage clamp electrophysiology data using a genetic algorithm. Using k-means clustering, we note eight clusters within 110 total parameter sets consisting of parameter solutions that provide a good fit to the experimental data. We then replicate novel fixed-voltage temperature ramp and fixed-temperature voltage ramp experimental data, demonstrating that our model can replicate the dynamic behaviors of TRPM8. With this TRPM8 gating model, we analyze the various parameter sets obtained from the genetic algorithm and find that different parameter combinations of calcium decay, calcium voltage shift of activation, and temperature sensitivity are able to match static voltage clamp data although differ in their effects on hysteresis and maximal current within prolonged temperature ramp simulations.
ContributorsDudebout, Eric (Author) / Crook, Sharon (Thesis director) / Van Horn, Wade (Committee member) / Barrett, The Honors College (Contributor) / School of Molecular Sciences (Contributor)
Created2024-05