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Neuroscience and Neurobiology

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Articles 121 - 150 of 164

Full-Text Articles in Medical Neurobiology

Analysis Of Diagnostic, Preventive, And Disease-Modifying Therapeutic Measures Of Alzheimer’S Disease, Ghazal Habib Havoutis Dec 2017

Analysis Of Diagnostic, Preventive, And Disease-Modifying Therapeutic Measures Of Alzheimer’S Disease, Ghazal Habib Havoutis

HCNSO Student Capstones

Alzheimer’s disease (AD) is the most common late-onset neurodegenerative disorder and cause of dementia, characterized by the formation of neurofibrillary tangles and senile plaque deposits. The heterogeneous nature of the disease (both genetically and environmentally) makes it difficult to prevent or cure. Without prevention, the prevalence of AD is expected to triple by 2050. However, because the diagnosis of AD is usually preceded by years of cognitive impairment, early detection may aid in reducing prevalence. Thus, there is a need for validated diagnostic measures for early and improved diagnosis and prevention. In this review, current and ongoing classifiers of early …


Exercise, Learning And Emotional Health: Interdisciplinary Approaches To Translational Action, Tessa L. Koschel Dec 2017

Exercise, Learning And Emotional Health: Interdisciplinary Approaches To Translational Action, Tessa L. Koschel

UNLV Theses, Dissertations, Professional Papers, and Capstones

Exercise positively effects physical, psychological and neurological wellbeing. Though the population at large is becoming increasingly aware of the multi-faceted benefits of exercise, the majority of people fail to meet daily exercise recommendations. Largely, demands of everyday life such as work, school and family take priority over fitness. The issue therefore becomes a matter of time. In a world of media multi-tasking and immediate gratification, the challenge to health professionals becomes incorporation and manipulation of these consistencies to improve exercise uptake and adherence. Focus must shift from the idea of making additional time for exercise, to adding exercise to time …


Thiamine Deficiency And Neurodegeneration: The Interplay Among Oxidative Stress, Endoplasmic Reticulum Stress, And Autophagy, Dexiang Liu, Zunji Ke, Jia Luo Sep 2017

Thiamine Deficiency And Neurodegeneration: The Interplay Among Oxidative Stress, Endoplasmic Reticulum Stress, And Autophagy, Dexiang Liu, Zunji Ke, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Thiamine (vitamin B1) is an essential nutrient and indispensable for normal growth and development of the organism due to its multilateral participation in key biochemical and physiological processes. Humans must obtain thiamine from their diet since it is synthesized only in bacteria, fungi, and plants. Thiamine deficiency (TD) can result from inadequate intake, increased requirement, excessive deletion, and chronic alcohol consumption. TD affects multiple organ systems, including the cardiovascular, muscular, gastrointestinal, and central and peripheral nervous systems. In the brain, TD causes a cascade of events including mild impairment of oxidative metabolism, neuroinflammation, and neurodegeneration, which are commonly observed in …


Rat Hind Limb Nociceptive Withdrawal Response To Heat And Mechanical Stimuli Depends On Initial Position Of The Paw But Not Stimulus Location, Giavanna Verdi May 2017

Rat Hind Limb Nociceptive Withdrawal Response To Heat And Mechanical Stimuli Depends On Initial Position Of The Paw But Not Stimulus Location, Giavanna Verdi

Senior Honors Projects, 2010-2019

Mammals rapidly withdraw their hind limb in response to noxious stimulation, which is a protective movement known as the nociceptive withdrawal response (NWR). The NWR has been previously studied in spinalized, decerebrated and anesthetized non-human and human mammals; however, there is minimal information on the NWR in intact, unanesthetized non-human mammals.

The first specific aim was to identify the factors that determine the direction and magnitude of the NWR in intact, unanesthetized rats. Based on previous studies, we hypothesized that the location of stimulation and the initial position of the paw preceding the NWR will influence the direction and magnitude …


An Evaluation Of Gabab Receptors On Modulating Neuroinflammation In A Non-Transgenic Animal Model Of Alzheimer's Disease, Monica Bolton May 2017

An Evaluation Of Gabab Receptors On Modulating Neuroinflammation In A Non-Transgenic Animal Model Of Alzheimer's Disease, Monica Bolton

UNLV Theses, Dissertations, Professional Papers, and Capstones

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive memory loss and distinct neuropathological hallmarks, including amyloid beta plaques and neurofibrillary tau tangles (NFT). Although the etiology remains to be discovered, several risk factors exist that significantly contribute to developing AD. Diabetes is one of the major risk factors associated with AD and is characterized by disrupted insulin signaling that may contribute to or exacerbate AD pathologies. Furthermore, both disorders result in increased neuroinflammation. Considerable evidence has demonstrated that a chronic inflammatory response, in particular chronic microglia activation, promotes A production as well as the hyperphosphorylation of tau through …


The Psychophysiological Correlates Of Personality, Trauma, Posttraumatic Stress Disorder And Social Support, Meghan E. Pierce May 2017

The Psychophysiological Correlates Of Personality, Trauma, Posttraumatic Stress Disorder And Social Support, Meghan E. Pierce

UNLV Theses, Dissertations, Professional Papers, and Capstones

Theories considering the etiology of psychopathy suggest that trauma exposure, specifically childhood maltreatment and sexual abuse, is related to the development of callous-unemotional traits in children and adolescents, which are precursors to psychopathic traits in adulthood. Furthermore, posttraumatic stress disorder has an opposite relationship with many of the emotional and behavioral components of the two-factor model of psychopathy. Specifically, PTSD is positively associated to IA and traits associated with it and negatively associated with FD. Thus, this study sought to expand upon the current theories of a trauma-based etiology of psychopathy by investigating the relationship between trauma, PTSD, and psychopathic …


Neural Processes Underlying Auditory Context Effects, Breanne Yerkes May 2017

Neural Processes Underlying Auditory Context Effects, Breanne Yerkes

UNLV Theses, Dissertations, Professional Papers, and Capstones

Auditory information within our natural environments is disorganized and often ambiguous, leaving our auditory systems with a complex task: organizing sound into coherent objects. The auditory system uses both current and prior information to assist in completing this task. The influences of previous context on current perception have been referred to as context effects. A contrastive context effect results in a current perception that is opposite of what is expected based on the physical stimulus properties presented during an immediate context. A facilitative context effect results in a current perception that is the same as the perception during the immediate …


Cerebellar Tdcs: A Novel Approach To Augment Language Treatment Post-Stroke, Rajani Sebastian, Sadhvi Saxena, Kyrana Tsapkini, Andreia V. Faria, Charltien Long, Amy Wright, Cameron Davis, Donna C. Tippett, Antonios P. Mourdoukoutas, Marom Bikson, Pablo Celnik, Argye E. Hillis Jan 2017

Cerebellar Tdcs: A Novel Approach To Augment Language Treatment Post-Stroke, Rajani Sebastian, Sadhvi Saxena, Kyrana Tsapkini, Andreia V. Faria, Charltien Long, Amy Wright, Cameron Davis, Donna C. Tippett, Antonios P. Mourdoukoutas, Marom Bikson, Pablo Celnik, Argye E. Hillis

Publications and Research

People with post-stroke aphasia may have some degree of chronic deficit for which current rehabilitative treatments are variably effective. Accumulating evidence suggests that transcranial direct current stimulation (tDCS) may be useful for enhancing the effects of behavioral aphasia treatment. However, it remains unclear which brain regions should be stimulated to optimize effects on language recovery. Here, we report on the therapeutic potential of right cerebellar tDCS in augmenting language recovery in SMY, who sustained bilateral MCA infarct resulting in aphasia and anarthria. We investigated the effects of 15 sessions of anodal cerebellar tDCS coupled with spelling therapy using a randomized, …


The Scripps Research Institute Summer Undergraduate Research Fellowship, Ezana Assefa Oct 2016

The Scripps Research Institute Summer Undergraduate Research Fellowship, Ezana Assefa

Trick to the Treat of Internships and Research

This program is a 10-week internship designed for undergraduates interested in the scientific field to engage in current research. Students have the option of requesting to work under three mentors, one of which they will be paired. Students will work in the lab with the principal investigator and other members of the lab. Along with working in the lab, students in the program will also attend bi-weekly talks/lectures from researchers, grad students, and professionals at TSRI as well as participating in two presentations and a final poster or oral presentation.


Zombies, Predatory Wasps And Consciousness, James K. Peterson Oct 2016

Zombies, Predatory Wasps And Consciousness, James K. Peterson

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.


Encoding Of Saltatory Tactile Velocity In The Adult Orofacial Somatosensory System, Rebecca Custead Jul 2016

Encoding Of Saltatory Tactile Velocity In The Adult Orofacial Somatosensory System, Rebecca Custead

College of Education and Human Sciences: Dissertations, Theses, and Student Research

Processing dynamic tactile inputs is a key function of somatosensory systems. Spatial velocity encoding mechanisms by the nervous system are important for skilled movement production and may play a role in recovery of motor function following neurological insult. Little is known about tactile velocity encoding in trigeminal networks associated with mechanosensory inputs to the face, or the consequences of movement.

High resolution functional magnetic resonance imaging (fMRI) was used to investigate the neural substrates of velocity encoding in the human orofacial somatosensory system during unilateral saltatory pneumotactile inputs to perioral hairy skin in 20 healthy adults. A custom multichannel, scalable …


Neurocalcin ẟ Response To Calcium: Which Ef Hand Matters The Most?, Trokon Fiawoo May 2016

Neurocalcin ẟ Response To Calcium: Which Ef Hand Matters The Most?, Trokon Fiawoo

Graduate School of Biomedical Sciences Theses and Dissertations

Changes in intracellular calcium levels play a very important role in cell signaling, in turn, affecting neuronal functions such as memory, learning and cell death. A class of proteins called Neuronal Calcium Sensor (NCS) proteins serves to modulate the functioning of the neuronal cells in response to changes in calcium levels. Structurally, all NCS proteins have 4 calcium-binding EF hand motifs, although EF I does not bind to calcium in many members. All NCS proteins are myristoylated at the N-terminus. Neurocalcin delta (NCALD) is an NCS protein, and shares 95% similarity in primary amino acid sequence with another major NCS …


Assessing Clinical Significance Of The Immediate Post-Concussion Assessment And Cognitive Testing Battery When Comparing Adjusted And Unadjusted Rci Methods For Different Ranges Of Baseline Scores, Ashley N. Figaro May 2016

Assessing Clinical Significance Of The Immediate Post-Concussion Assessment And Cognitive Testing Battery When Comparing Adjusted And Unadjusted Rci Methods For Different Ranges Of Baseline Scores, Ashley N. Figaro

UNLV Theses, Dissertations, Professional Papers, and Capstones

The growing concern revolving around the dangers of sports-related concussions have led to the most recent implementation of neurocognitive (NC) test batteries as a means to objectively determine the presence of a cognitive defect. Whereas any other sports-related injury can be diagnosed with tools such as an x-ray or MRI, a concussion represents a metabolic disturbance that cannot be identified by these diagnostic tools. Many neurocognitive test batteries employ statistical techniques to derive cut off scores in order to represent significant or insignificant changes as compared to individual baseline scores, or pre-established normative values. If an individuals’ post-injury score exceeds …


Cannabinoid Receptor Interacting Protein Suppresses Agonist-Driven Cb1 Receptor Internalization And Regulates Receptor Replenishment In An Agonist-Biased Manner, Lawrence C. Blumes, Sandra Leone-Kabler, Deborah J. Luessen, Glenn S. Marrs, Erica Lyons, Caroline E. Bass, Rong Chen, Dana E. Selley, Allyn C. Howlett Jan 2016

Cannabinoid Receptor Interacting Protein Suppresses Agonist-Driven Cb1 Receptor Internalization And Regulates Receptor Replenishment In An Agonist-Biased Manner, Lawrence C. Blumes, Sandra Leone-Kabler, Deborah J. Luessen, Glenn S. Marrs, Erica Lyons, Caroline E. Bass, Rong Chen, Dana E. Selley, Allyn C. Howlett

Neurology Publications

Cannabinoid receptor interacting protein 1a (CRIP1a) is a CB1 receptor (CB1R) distal C-terminus-associated protein that modulates CB1R signaling via G proteins, and CB1R down-regulation but not desensitization (Blume et al. [2015] Cell Signal., 27, 716-726; Smith et al. [2015] Mol. Pharmacol., 87, 747-765). In this study, we determined the involvement of CRIP1a in CB1R plasma membrane trafficking. To follow the effects of agonists and antagonists on cell surface CB(1)Rs, we utilized the genetically homogeneous cloned neuronal cell line N18TG2, which endogenously expresses both CB1R and CRIP1a, and exhibits a well-characterized endocannabinoid signaling system. We developed stable CRIP1a-over-expressing and CRIP1a-siRNA-silenced knockdown …


The Effect Of Caffeine On Migraine Headaches, Deborah Shimshoni Jan 2016

The Effect Of Caffeine On Migraine Headaches, Deborah Shimshoni

Honors Undergraduate Theses

As the most widely consumed drug around the globe, there is a vast array of contradicting research available on caffeine. One of the most debated and researched topics on caffeine is its effect on the brain. Meanwhile, the data on the neurological condition of migraine has information scattered throughout countless research articles and experiments.

Although neither migraine or caffeine are completely understood by the medical world, this analysis attempts to give a more coherent understanding of the relationship between the two. This is done by first understanding the known and theorized mechanisms of caffeine as well as the pathologies of …


Isoflurane Inhibits Synaptic Vesicle Exocytosis Through Reduced Ca2+ Influx, Not Ca2+-Exocytosis Coupling, Joel Baumgart, Zhen-Yu Zhou, Masato Hara, Daniel Cook, Michael Hoppa Sep 2015

Isoflurane Inhibits Synaptic Vesicle Exocytosis Through Reduced Ca2+ Influx, Not Ca2+-Exocytosis Coupling, Joel Baumgart, Zhen-Yu Zhou, Masato Hara, Daniel Cook, Michael Hoppa

Dartmouth Scholarship

Identifying presynaptic mechanisms of general anesthetics is critical to understanding their effects on synaptic transmission. We show that the volatile anesthetic isoflurane inhibits synaptic vesicle (SV) exocytosis at nerve terminals in dissociated rat hippocampal neurons through inhibition of presynaptic Ca2+ influx without significantly altering the Ca2+ sensitivity of SV exocytosis. A clinically relevant concentration of isoflurane (0.7 mM) inhibited changes in [Ca2+]i driven by single action potentials (APs) by 25 ± 3%, which in turn led to 62 ± 3% inhibition of single AP-triggered exocytosis at 4 mM extracellular Ca2+ ([Ca2+]e). Lowering external Ca2+ to match the isoflurane-induced reduction in …


The Effect Of Sleep On Perceptual Learning And Memory Consolidation, Vanessa Claire Irsik Aug 2015

The Effect Of Sleep On Perceptual Learning And Memory Consolidation, Vanessa Claire Irsik

UNLV Theses, Dissertations, Professional Papers, and Capstones

An ability to segregate speech accurately is essential given that most auditory environments contain other overlapping conversations or environmental noise. While perceiving speech among background noise can be difficult in and of itself, those with hearing impairments can experience considerable difficulty. While training has been shown to benefit perceptual segregation of trained sounds, it is unclear how such training transfers to sounds not included in a training regimen. The current study aimed to address this question by training listeners on a portion of sounds during a vowel segregation task, and subsequently testing on both the trained sounds and untrained sounds. …


Functional Capacity In Schizophrenia: Relationship Among Effort, Reinforcement Learning And Self-Beliefs, Sally J. Vogel May 2015

Functional Capacity In Schizophrenia: Relationship Among Effort, Reinforcement Learning And Self-Beliefs, Sally J. Vogel

UNLV Theses, Dissertations, Professional Papers, and Capstones

Individuals with schizophrenia exhibit a wide range of complex neurocognitive, psychiatric and behavioral impairments. Recent research suggests that this complex array of symptoms can be at least partially accounted for by dysfunction in more basic mechanisms, such as the ability to learn from positive and negative reinforcement, or the ability to exert adequate effort when completing simple tasks. Evidence also suggests that deficits in these basic mechanisms may contribute to more complex symptoms, such as functional impairment. Also, the relationship between neurocognitive deficits and functional impairment has been found to be mediated by defeatist performance beliefs. However, studies have not …


A Comparison Of The Effects Of Different Doses Of Gabab Receptor Ligands On Spatial Learning And Memory And Memory Flexibility, Chelcie Heaney May 2015

A Comparison Of The Effects Of Different Doses Of Gabab Receptor Ligands On Spatial Learning And Memory And Memory Flexibility, Chelcie Heaney

UNLV Theses, Dissertations, Professional Papers, and Capstones

The principal inhibitory neurotransmitter in the brain, gamma amino-butyric acid (GABA), mediates several types of learning and memory. Of the two main receptor subtypes for GABA, the in vivo role of GABAB receptor in learning and memory is less well characterized and the current data often conflict. Based on the current literature, it is unclear, for instance, whether enhancing GABAergic activity via the GABAB receptor could be beneficial for or detrimental to learning and memory. Hippocampally-dependent learning and memory tasks are of particular interest due to their clinical relevance to patients with schizophrenia or Alzheimer’s disease, who exhibit impaired performance …


Brain Blast 2015 Speakers Poster, Annie Leslie Mar 2015

Brain Blast 2015 Speakers Poster, Annie Leslie

Brain Blast

Poster from UNE's Brain Blast 2015 listing the expected presenters at this event.*


Exposure To Kynurenic Acid During Adolescence Increases Sign-Tracking And Impairs Long-Term Potentiation In Adulthood, Nicole E. Deangeli, Travis P. Todd, Stephen E. Chang, Hermes H. Yeh, Pamela W. Yeh, David J. Bucci Jan 2015

Exposure To Kynurenic Acid During Adolescence Increases Sign-Tracking And Impairs Long-Term Potentiation In Adulthood, Nicole E. Deangeli, Travis P. Todd, Stephen E. Chang, Hermes H. Yeh, Pamela W. Yeh, David J. Bucci

Dartmouth Scholarship

Changes in brain reward systems are thought to contribute significantly to the cognitive and behavioral impairments of schizophrenia, as well as the propensity to develop co-occurring substance abuse disorders. Presently, there are few treatments for persons with a dual diagnosis and little is known about the neural substrates that underlie co-occurring schizophrenia and substance abuse. One goal of the present study was to determine if a change in the concentration of kynurenic acid (KYNA), a tryptophan metabolite that is increased in the brains of people with schizophrenia, affects reward-related behavior. KYNA is an endogenous antagonist of NMDA glutamate receptors and …


Targeting Methylglyoxal And Ppar Gamma To Alleviate Neuropathic Pain Associated With Type 2 Diabetes, Ryan B. Griggs Jan 2015

Targeting Methylglyoxal And Ppar Gamma To Alleviate Neuropathic Pain Associated With Type 2 Diabetes, Ryan B. Griggs

Theses and Dissertations--Physiology

Neuropathic pain affects up to 50% of the 29 million diabetic patients in the United States. Neuropathic pain in diabetes manifests as a disease of the peripheral and central nervous systems. The prevalence of type 2 diabetes is far greater than type 1 (90%), yet the overwhelming focus on type 1 models this has left the mechanisms of pain in type 2 diabetes largely unknown. Therefore I aimed to improve the current mechanistic understanding of pain associated with type 2 diabetes using two preclinical rodent models: Zucker Diabetic Fatty rats and db/db mice. In addition, I highlight the translational importance …


Enhanced Cgmp-Dependent Signaling In Astrocytes: Novel Therapeutic Target In Alzheimer's Disease, Nyema M. Woart Jan 2015

Enhanced Cgmp-Dependent Signaling In Astrocytes: Novel Therapeutic Target In Alzheimer's Disease, Nyema M. Woart

PCOM Biomedical Studies Student Scholarship

Over five million Americans suffer from Alzheimer’s Disease (AD), with an expected 34% increase in the incidence in this disease over the next decade. Unfortunately, there is no cure for AD. Recent studies have indicated that drugs which increase the levels of cyclic guanosine-3’5’-monophosphate (cGMP) may help preserve learning and memory in AD and enhance cognition in the aging brain; however, the mechanism(s) of how cGMP exerts this beneficial effect is unknown. The present findings now suggest that elevation of cGMP in astrocytes depresses inhibitory potassium currents in these cells to stimulate their protective influence on neuronal activity. Cellular currents …


Gene Expression And Alzheimer's Disease: Evaluation Of Gene Expression Patterns In Brain And Blood For An Alzheimer's Disease Mouse Model, Amanda Hazy Jan 2015

Gene Expression And Alzheimer's Disease: Evaluation Of Gene Expression Patterns In Brain And Blood For An Alzheimer's Disease Mouse Model, Amanda Hazy

Senior Honors Theses

Previous studies have established a causative role for altered gene expression in development of Alzheimer’s disease (AD). These changes can be affected by methylation and miRNA regulation. In this study, expression of miRNA known to change methylation status in AD was assessed by qPCR. Genome-wide expression changes were determined by RNA-sequencing of mRNA from hippocampus and blood of control and AD mice. The qPCR data showed significantly increased expression of Mir 17 in AD, and sequencing data revealed 230 genes in hippocampus, 58 genes in blood, and 8 overlapping genes showing significant differential expression (p value ≤ 0.05). Expression data …


Postural Sway And Brain Hemispheric Power Spectral Density Under Different Attentional Focus Conditions, Sharon Jalene Dec 2014

Postural Sway And Brain Hemispheric Power Spectral Density Under Different Attentional Focus Conditions, Sharon Jalene

UNLV Theses, Dissertations, Professional Papers, and Capstones

The purpose of this study was to determine the differences, if any, in the root mean square error (RMSE) of postural sway and hemispheric power spectral density (PSD) in the alpha and beta bands (8-12Hz and 12-25Hz) during different conditions of attentional focus (i.e., internal focus (IF), and external focus (EF) and a control condition (C)). Previous studies have shown that the adoption of IF and EF significantly alter motor performance and that EF promotes automaticity (Wulf, 2013). Sports performance and balance studies utilizing EEG spectral analyses report increased alpha oscillations during expert performance and stable balance and increased beta …


Hemispheric Asymmetry In The Perception Of Musical Pitch Structure, Matthew Adam Rosenthal Dec 2014

Hemispheric Asymmetry In The Perception Of Musical Pitch Structure, Matthew Adam Rosenthal

UNLV Theses, Dissertations, Professional Papers, and Capstones

Both the left and right hemispheres contribute to the perception of pitch structure

in music. Music researchers have attempted to explain the observed asymmetries in the perception of musical pitch structure by characterizing the dominant processing style of each hemisphere. However, no existing characterizations have been able to account for all of the empirical findings. To better explain existing empirical findings, this dissertation characterizes the left hemisphere as dominant in temporal pitch processing (i.e. with respect to the sequential ordering of pitches) and the right hemisphere as dominant in non-temporal pitch processing (i.e. without respect to the sequential ordering of …


Analysis Of Differential Mrna And Mirna Expression In An Alzheimer’S Disease Mouse Model, Amanda Hazy, Matthew Dalton Oct 2014

Analysis Of Differential Mrna And Mirna Expression In An Alzheimer’S Disease Mouse Model, Amanda Hazy, Matthew Dalton

Other Undergraduate Scholarship

Research has shown that changes in gene expression play a critical role in the development of Alzheimer’s Disease (AD). Our project will evaluate genome-wide RNA expression patterns from brain and blood in an AD mouse model. This analysis will provide insight regarding the mechanisms of AD pathology as well as determine a possible diagnostic tool utilizing RNA expression patterns found in the blood as biomarkers for AD.


The Effect Of Acute Lps-Induced Immune Activation And Brain Insulin Signaling Disruption In A Diabetic Model Of Alzheimer's Disease, Andrew Scott Murtishaw Aug 2014

The Effect Of Acute Lps-Induced Immune Activation And Brain Insulin Signaling Disruption In A Diabetic Model Of Alzheimer's Disease, Andrew Scott Murtishaw

UNLV Theses, Dissertations, Professional Papers, and Capstones

Alzheimer's disease (AD) is a neurodegenerative disorder marked by progressive cognitive impairments and pathological hallmarks that include amyloid plaques, neurofibrillary tangles, and neuronal loss. Several well-known mutations exist that lead to early-onset familial AD (fAD). However, these cases only account for a small percentage of total AD cases. The vast majority of AD cases are sporadic in origin (sAD) and are less clearly influenced by a single mutation but rather some combination of genetic and environmental risk.

The etiology of sAD remains unclear but numerous risk factors have been identified that increase the chance of developing AD. Among these risk …


Fty720 (Fingolimod) Provides Insight Into The Molecular Mechanisms Of Multiple Sclerosis, Madelyn Elizabeth Crawford Jun 2014

Fty720 (Fingolimod) Provides Insight Into The Molecular Mechanisms Of Multiple Sclerosis, Madelyn Elizabeth Crawford

Pursuit - The Journal of Undergraduate Research at The University of Tennessee

Multiple sclerosis (MS) is a neurodegenerative disorder caused by a prolonged immune- mediated inflammatory response that targets myelin. Nearly all of the drugs approved for the treatment of MS are general immunosuppressants or only function in symptom management. The oral medication fingolimod, however, is reported to have direct therapeutic effects on cells of the central nervous system in addition to immunomodulatory functions. Fingolimod is known to interact with sphingosine-1-phosphate (S1P) receptors, and the most widely- accepted theory for its mechanism of action is functional antagonism of the receptor. This review examines significant neuromodulatory effects achieved by functional antagonism of the …


Fatty Acids Increase Neuronal Hypertrophy Of Pten Knockdown Neurons, Catherine J. Fricano, Tyrone Despenza, Paul W. Frazel, Meijie Li, A. James O'Malley, Gary Westbrook, Bryan Luikart Apr 2014

Fatty Acids Increase Neuronal Hypertrophy Of Pten Knockdown Neurons, Catherine J. Fricano, Tyrone Despenza, Paul W. Frazel, Meijie Li, A. James O'Malley, Gary Westbrook, Bryan Luikart

Dartmouth Scholarship

Phosphatase and tensin homolog (Pten) catalyzes the reverse reaction of PI3K by dephosphorylating PIP3 to PIP2. This negatively regulates downstream Akt/mTOR/S6 signaling resulting in decreased cellular growth and proliferation. Co-injection of a lentivirus knocking Pten down with a control lentivirus allows us to compare the effects of Pten knockdown between individual neurons within the same animal. We find that knockdown of Pten results in neuronal hypertrophy by 21 days post-injection. This neuronal hypertrophy is correlated with increased p-S6 and p-mTOR in individual neurons. We used this system to test whether an environmental factor that has been implicated in cellular hypertrophy …