Neurosciences Commons^™

Aβ Alters The Dna Methylation Status Of Cell-Fate Genes In An Alzheimer’S Disease Model, Gary D. Isaacs, Noor Taher, Courtney Mckenzie, Rebecca Garrett, Matthew Baker, Nena Fox

Faculty Publications and Presentations

Alzheimer’s disease (AD) is characterized by neurofibrillary tangles and extracellular amyloid-β plaques (Aβ). Despite ongoing research, some ambiguity remains surrounding the role of Aβ in the pathogenesis of this neurodegenerative disease. While several studies have focused on the mutations associated with AD, our understanding of the epigenetic contributions to the disease remains less clear. To that end, we determined the changes in DNA methylation in differentiated human neurons with and without Aβ treatment. We isolated the DNA from neurons treated with Aβ or vehicle, and digested the two samples with either a methylation-sensitive (HpaII) or a methylation-insensitive (MspI) restriction endonuclease. …

A Neurophysiological Examination Of Stress Control In Martial Artists, Jack Pemment

Electronic Theses and Dissertations

The philosophies behind many martial arts often claim that by practicing martial arts individuals can gain better control over stress. We tested this idea by using controlled physical stressors to elicit an acute stress response from martial artists (n=15) and non-martial artists (n=18). To measure the extent of the stress response, we looked at changes in heart rate, respiratory sinus arrhythmia, and galvanic skin level. These three measures explore both parasympathetic and sympathetic responses, and changes in these variables continue to be explored in studies of stress and reactive aggression. In addition to our physical stressors we also exposed individuals …

Studies Of Regulated Exocytosis From Neuroendocrine Cells, Madhurima Das

Wayne State University Theses

In this thesis we study cargo release and fusion pore dilation during calcium triggered exocytosis and the co-localization of calcium sensing proteins essential for exocytosis, in neuroendocrine cells.

Pancreatic beta cells secrete several hormones, the most studied one being insulin. C-peptide is a protein which is co-stored with and secreted from the same vesicles as insulin. It is found in the soluble phase unlike insulin, which is found in the dense core. The pancreatic beta cells also secrete the Chromogranin B (CgB) which is mostly found in the dense cores of secretory vesicles. In chapter 1, we found that CgB, …

Effects Of Intranasally Administered Dnsp-11 On The Central Dopamine System Of Normal And Parkinsonian Fischer 344 Rats, James H. Sonne

Theses and Dissertations--Neuroscience

Due to the blood-brain barrier, delivery of many drugs to the brain has required intracranial surgery which is prone to complication. Here we show that Dopamine Neuron Stimulating Peptide 11 (DNSP-11), following non-invasive intranasal administration, protects dopaminergic neurons from a lesion model of Parkinson’s disease in the rat. A significant and dose-dependent increase in an index of dopamine turnover (the ratio of DOPAC to dopamine) was observed in the striatum of normal young adult Fischer 344 rats by whole-tissue neurochemistry compared to vehicle administered controls.

Among animals challenged with a moderate, unilateral 6-hydroxy-dopamine (6-OHDA) lesion of the substantia nigra, those …

Inhibition Of Calpains By Calpastatin: Implications For Cellular And Functional Damage Following Traumatic Brain Injury, Kathleen M. Schoch

Theses and Dissertations--Physiology

Traumatic brain injury (TBI) is a devastating health problem based on its high incidence, economic burden, and lack of effective pharmacological treatment. Individuals who suffer an injury often experience lifelong disability. TBI results in abrupt, initial cell damage leading to delayed neuronal death. The calcium-activated proteases, calpains, are known to contribute to this secondary neurodegenerative cascade. Prolonged activation of calpains results in proteolysis of numerous cellular substrates including cytoskeletal components, membrane receptors, and cytosolic proteins, contributing to cell demise despite coincident expression of calpastatin, the specific inhibitor of calpains.

A comprehensive analysis using two separate calpastatin transgenic mouse lines was …

Evaluation Of Insulin-Like Growth Factor-1 As A Therapeutic Approach For The Treatment Of Traumatic Brain Injury, Shaun W. Carlson

Theses and Dissertations--Physiology

Traumatic brain injury (TBI) is a prevalent CNS neurodegenerative condition that results in lasting neurological dysfunction, including potentially debilitating cognitive impairments. Despite the advancements in understanding the complex damage that can culminate in cellular dysfunction and loss, no therapeutic treatment has been effective in clinical trials, highlighting that new approaches are desperately needed. A therapy that limits cell death while simultaneously promoting reparative mechanisms, including post-traumatic neurogenesis, in the injured brain may have maximum effectiveness in improving recovery of function after TBI. Insulin-like growth factor-1 (IGF-1) is a potent growth factor that has previously been shown to promote recovery of …

Microglia Activation In A Rodent Model Of An Alcohol Use Disorder: The Importance Of Phenotype, Initiation, And Duration Of Activation, Simon A. Marshall

Theses and Dissertations--Pharmacy

Chronic ethanol exposure results in neuroadaptations that drive the progression of an alcohol use disorder (AUD). One such driving force is alcohol-induced neurodegeneration. Neuroinflammation has been proposed as a mechanism underlying this damage. Although neuroinflammation is a physiological response to damage, overactivation of its pathways can lead to neurodegeneration. A hallmark indicator of neuroinflammation is microglial activation, but microglial activation is a heterogeneous continuum of phenotypes that can promote or inhibit neuroinflammation. Furthermore acute microglial activation is necessary to restore homeostasis, but prolonged activation can exacerbate damage. The diversity of microglia makes both the level and timecourse of activation vital …

Thc-Mediated Induction Of Δfosb And Its Modulation Of Cb1r Signaling And Adaptation, Lazenka Matthew

Theses and Dissertations

The main psychoactive and therapeutic effects of Δ9-tetrahydrocannabinol (THC) are mediated through cannabinoid type 1 receptors (CB1Rs). The therapeutic uses of THC are mitigated by the development of tolerance to these therapeutic effects, whereas tolerance does not readily develop to some of the side-effects of THC, like motor impairment and reward. The development of tolerance occurs through adaptations at CB1Rs, which include desensitization (G-protein uncoupling) and downregulation (receptor degradation). Brain region-dependent differences in THC-mediated adaptations are proposed to explain the differences in tolerance to various THC-mediated effects. These studies focused on whether ΔFosB, a stable transcription factor, could regulate CB1R …

Progress Towards Understanding Of Mechanisms Of Action Of Potent Multifunctional Disease Modifying Therapeutics For Parkinson's Disease & Investigating The Methamphetamine-Induced Striatal Microglia Activation., Mrudang M. Shah

Wayne State University Dissertations

PROGRESS TOWARDS UNDERSTANDING OF MECHANISMS OF ACTION OF POTENT MULTIFUNCTIONAL DISEASE MODIFYING

THERAPEUTICS FOR PARKINSON'S DISEASE.

by

MRUDANG MANOJKUMAR SHAH

December 2013

Advisor: Dr. Aloke Dutta

Major: Pharmaceutical Sciences

Degree: Doctor of Philosophy

Our long term goal is to design and develop potent multifunctional disease modifying therapeutics for Parkinson's disease. The objective of my dissertation was to understand the mechanisms of action of some potent small molecules (synthesized in our lab) as a disease modifying Parkinson's disease therapeutic. The objective was achieved by pursuing the following two specific aims:

1. Investigating anti-oxidant and neuroprotective effects of a lead molecule (D-512) …

Effects Of Electrical Stimulation And Testosterone In Translational Models Of Peripheral Nerve Injury, Gina Monaco

Dissertations

As functional recovery following peripheral nerve injury is dependent upon successful regeneration and target reconnection, combinatorial treatments that enhance different regeneration events may be required for recovery from severe injuries. The neurotherapeutic effects of electrical stimulation (ES) and gonadal steroids have been demonstrated independently and in combination in extratemporal and intratemporal facial nerve injuries. The goals of the first aim were to develop a reliable intracranial facial nerve crush model and to investigate the therapeutic potential of combining ES with testosterone propionate (TP) in this most proximal injury model. Adult male rats were divided into intracranial sham-operated, intracranial crush, and …

Neurocognitive Function Declines Following Migraine Headache In College Students, Marguerite Moore, T. Covassin, K.A. Pfeiffer, R.E. Norris, R.L. Jensen, C.F. Branta

Journal Articles

No abstract provided.

Sites Of Alcohol Action At The Glun1/Glun2b Nmda Receptor M3-M4 Domain Intersubunit Interfaces, Yuanhao Zhao, M. Wu, Hong Ren, Robert W. Peoples

Biomedical Sciences Faculty Research and Publications

The N-methyl-D-aspartate (NMDA) receptor has been shown to be one of the most important target sites of alcohol in the central nervous system. We and others have identified positions in the third and fourth membrane-associated (M) domains of both GluN1 and GluN2A subunits that influence alcohol sensitivity. In the structural model of the NMDA receptor based upon the related GluA2 receptor, the outward face of the M3 domain of one subunit type is oriented toward the M4 domain of the other subunit type. We recently reported that four pairs of alcohol-sensitive amino acid positions in GluN1/GluN2A NMDA receptors interact at …

Identification Of Phosphorylation Sites In The Cooh-Terminal Tail Of The Μ-Opioid Receptor., Ying-Ju Chen, Sue Oldfield, Adrian J. Butcher, Andrew B. Tobin, Kunal Saxena, Vsevolod V. Gurevich, Jeffrey L. Benovic, Graeme Henderson, Eamonn Kelly

Department of Biochemistry and Molecular Biology Faculty Papers

Phosphorylation is considered a key event in the signalling and regulation of the μ opioid receptor (MOPr). Here, we used mass spectroscopy to determine the phosphorylation status of the C-terminal tail of the rat MOPr expressed in human embryonic kidney 293 (HEK-293) cells. Under basal conditions, MOPr is phosphorylated on Ser(363) and Thr(370), while in the presence of morphine or [D-Ala2, NMe-Phe4, Gly-ol5]-enkephalin (DAMGO), the COOH terminus is phosphorylated at three additional residues, Ser(356) , Thr(357) and Ser(375). Using N-terminal glutathione S transferase (GST) fusion proteins of the cytoplasmic, C-terminal tail of MOPr and point mutations of the same, we …

The Mesocorticolimbic Dopamine Pathway Reconstituted In Vitro: Glutamate Receptors And Corticosteroid-Methamphetamine Neurotoxicity, Jennifer N. Berry

Theses and Dissertations--Psychology

Stress promotes the use of methamphetamine and other recreational substances and is often implicated in relapse to stimulant use. Thus, it is of critical importance to examine the consequences of the co-occurance of stress and methamphetamine use. Activity of the glutamatergic N-methyl D-aspartate (NMDA) receptor system appears to be involved in the neurotoxic effects of both chronic stress and methamphetamine exposure. The current studies investigated the hypothesis that chronic pre-exposure to the stress hormone corticosterone (CORT) results in an increase of NMDA receptor activity and that this will potentiate the neurotoxic effects of methamphetamine (METH). Co-cultures of the …

Binge Alcohol And Recovery After Traumatic Brain Injury, Ian Vaagenes

Dissertations

An estimated 275,000 Americans are hospitalized following a traumatic brain injury (TBI) every year, 80,000 of whom develop a long-term disability. The factor that places one at perhaps the greatest risk of suffering a TBI is alcohol intoxication. 30-50% of TBI sufferers have a blood alcohol level above .08 mg/dl at the time of injury, the legal limit in most U.S. states. In fact, the presence of alcohol at the time of TBI more than doubles the risk of a repeat head injury in the two years following the injury. Given the large population of TBI sufferers with alcohol intoxication …

Influence Of Pramipexole On Probability Discounting And Ventral Pallidal Function: Assessments In Parkinsonian-Like Rats, Sandra Lynn Rokosik-Kletzel

Dissertations

People with neuropathologies who are treated with dopamine agonists may be at risk to develop impulse control disorders. The overall goal of this dissertation project was to expand our knowledge on the neuropsychopharmacology of dopamine agonist-induced impulsivity. At the time this dissertation was being developed, pramipexole was the drug, gambling was the behavior, and Parkinson's disease (PD) was the pathology most widely reported for this phenomenon. Therefore, we first developed a behavioral paradigm (i.e., probability discounting) to measure risk-taking, one aspect of gambling. Utilizing this paradigm, we determine if risk-taking was altered after acute and/or chronic pramipexole treatment. We incorporated …

Alpha-Synuclein Aggregates Activate The Nlrp3 Inflammasome Following Vesicle Rupture, Rudy Orlando Cedillos

Master's Theses

Parkinson's disease (PD) and related synucleinopathies are progressive neurodegenerative disorders that feature the accumulation of intracellular inclusions known as Lewy bodies (LBs) in the brain. The presynaptic protein α-synuclein is the primary constituent of LBs and has been documented to play a major role in the pathogenesis of synucleinopathies. Recently, aggregated α-synuclein has been implicated in prompting microglia-mediated inflammation, a process associated with the progression of neuronal death in neurodegenerative disorders. Although the mechanisms surrounding the induction of neuroinflammation are not well understood, the recently discovered inflammasome-forming NLR proteins have emerged as regulators of inflammation. In this study, we sought …

P900: A Putative Novel Erp Component That Indexes Counter-Measure Use In The P300-Based Concealed Information Test, John B. Meixner Jr., Elena Labkovsky, J. Peter Rosenfeld, Michael R. Winograd, Michael Winograd, Alexander Sokolovsky, Jeff Weishaar, Tim Ullmann

Scholarly Works

Countermeasures pose a serious threat to the effectiveness of the Concealed Information Test (CIT). In a CIT experiment, Rosenfeld and Labkovsky in Psychophysiology 47(6):1002–1010, (2010) observed a previously unknown positive ERP component at about 900 ms poststimulus at Fz and Cz that could potentially serve as an index of countermeasure use. Here, we explored the hypothesis that this component, termed P900, occurs in response to a signal that no further specific response is required in a trial, and could thus appear in countermeasure users that respond differentially depending on the stimulus that appears. In the present experiments, subjects viewed four …

Retinal Vascular Biomarkers For Early Detection And Monitoring Of Alzheimer's Disease, Shawn Frost, Yogi Kanagasingam, Hamid Sohrabi, J Vignarajan, P Bourgeat, Olivier Salvado, Victor Villemagne, Christopher Rowe, S Lance Macaulay, Cassandra Szoeke, Kathryn A. Ellis, David Ames, Colin L. Masters, Stephanie Rainey-Smith, Ralph N. Martins

Research outputs 2013

The earliest detectable change in Alzheimer's disease (AD) is the buildup of amyloid plaque in the brain. Early detection of AD, prior to irreversible neurological damage, is important for the efficacy of current interventions as well as for the development of new treatments. Although PiB-PET imaging and CSF amyloid are the gold standards for early AD diagnosis, there are practical limitations for population screening. AD-related pathology occurs primarily in the brain, but some of the hallmarks of the disease have also been shown to occur in other tissues, including the retina, which is more accessible for imaging. Retinal vascular changes …

Multiplex Biomarkers In Blood, Veer Bala Bala Gupta, Ramani Sundaram, Ralph N. Martins

Research outputs 2013

Advances in the field of blood biomarker discovery will help in identifying Alzheimer's disease in its preclinical stage, allowing treatment to be initiated before irreversible damage occurs. This review discusses some recent past and current approaches being taken by researchers in the field. Individual blood biomarkers have been unsuccessful in defining the disease pathology, progression and thus diagnosis. This directs to the need for discovering a multiplex panel of blood biomarkers as a promising approach with high sensitivity and specificity for early diagnosis. However, it is a great challenge to standardize a worldwide blood biomarker panel due to the innate …

Design, Manufacturing, And Assembly Of A Flexible Thermoelectric Device, Christopher Anthony Martinez

USF Tampa Graduate Theses and Dissertations

This thesis documents the design, manufacturing, and assembly of a flexible thermoelectric device. Such a device has immediate use in haptics, medical, and athletic applications. The governing theory behind the device is explained and a one dimensional heat transfer model is developed to estimate performance. This model and consideration for the manufacturing and assembly possibilities are the drivers behind the decisions made in design choices. Once the design was finalized, manufacturing methods for the various components were explored. The system was created by etching copper patterns on a copper/polyimide laminate and screen printing solder paste onto the circuits. Thermoelectric elements …

The Role Of Molecular Chaperones In The Etiology And Treatment Of Psychiatric Diseases In The Elderly, John Clarence O'Leary

USF Tampa Graduate Theses and Dissertations

The elderly are at increased risk for developing psychiatric diseases, which include Alzheimer's disease, depression, anxiety and suicide. The probability of multiple disease comorbidity is also increased in the elderly. At the cellular level, the loss of protein homeostasis is often at the root of disease emergence, and thus the scientific community is searching for ways to help maintain this balance. A vast group of proteins that are paramount to balancing and counterbalancing protein levels is the molecular chaperone protein group, which has evolved a tremendous variety of functions in the cell. They aid in protein trafficking, folding, receptor signaling, …

The Inflammatory Response Initiated By The Spleen To Ischemic Stroke, Hilary Seifert

USF Tampa Graduate Theses and Dissertations

The peripheral immune system plays a role in delayed neural injury after stroke. This response originates from the spleen as splenectomy prior to middle cerebral artery occlusion (MCAO) in rats significantly reduces infarct volume in the brain. This research is based on the hypothesis that inhibiting the splenic response will reduce neurodegeneration after stroke. Studies in animals have implicated lymphocytes as the immune cell type that is detrimental following MCAO. Interferon gamma (IFNγ) has been identified as a pro-inflammatory cytokine that is also detrimental following stroke. IFNγ is important because it activates microglia and macrophages in a pro-inflammatory nature that …

Molecular And Cellular Mechanisms Of Reelin Signaling In The Adult Hippocampus, Justin Howard Trotter

USF Tampa Graduate Theses and Dissertations

The Reelin signaling pathway is critical for neuronal migration during development and the function of excitatory synapses in the adult forebrain. Despite a growing body of evidence implicating impaired Reelin signaling in the pathogenesis of numerous neuropsychiatric and neurodegenerative disorders, including Schizophrenia and Alzheimer's disease, little is known still regarding the specific molecular and cellular mechanisms whereby Reelin signaling modulates the function of synapses to enable normal learning and memory. In this dissertation, we addressed these knowledge gaps by identifying mechanisms of Reelin proteolysis following synaptic potentiation (Chapter 2) and dissociated the synaptic function of Reelin signaling at excitatory (Chapter …

Diet-Induced Ketosis And Calorie Restriction In Mouse Models Of Alzheimer's Pathology, Milene Lara Brownlow

USF Tampa Graduate Theses and Dissertations

Dietary manipulations and their pharmacological outcomes have been increasingly studied in neurodegenerative diseases. However, a systematic comparison among different methods in validated animal models of Alzheimer's disease is made necessary due to several different approaches applied in recent studies. Moreover, despite the large body of evidence on the effects of calorie restriction (CR) and ketogenic diets (KDs) on amyloid pathology, no consistent data is available on the effects of calorie restriction, ketogenic diet or ketone supplements on tau pathology in transgenic models of AD. Moreover, the ketogenic diet used in our studies was custom made with low carbohydrate content and …

Functional Near Infrared Detection Of Real And Imagined Finger Taps Using Support Vector Machine, Linear Discriminant Analysis, And Decision Tree Classification Methods, Eugene A. Stoudenmire

Computational Modeling & Simulation Engineering Theses & Dissertations

This study investigates the thesis that given cerebral response samples of an individual's left, right, both, and imagined finger tapping, continuous wave (CW) functional Near Infrared (fNIR), unregistered with fMRI, can differentiate between any two of the four categories.

Fifty subjects were outfitted with a single source/detector attached to a single, square pad, affixed to their heads using devices such as elastic bands and caps for light shielding. Slides depicting arrows pointing left, right, both directions, or made of dashed lines were presented to each subject, with a slide of text interspersed between each. Subjects tapped with their left finger, …

The Effects Of Temporal Preparation On Reaction Time, Glen Robert Forester

USF Tampa Graduate Theses and Dissertations

When responding to external stimuli, preparation reduces Reaction Time (RT). One form of preparation known as temporal preparation results from advance knowledge about when a stimulus will appear. We used Event Related Potentials to investigate how increasing temporal preparation decreases RT during a speeded, choice RT task by manipulating temporal preparation within subjects. In order to determine which cognitive processes are speeded, the latencies of the Lateralized Readiness Potential (LRP) and P300 were examined across two levels of temporal preparation. In line with previous research the stimulus locked LRP, but not the response locked LRP, was speeded when temporal preparation …

Proteolytic Processing Of The Amyloid Precursor Protein During Apoptosis And Cell Cycle: Implications For Alzheimer's Disease, Tina N. Fiorelli

USF Tampa Graduate Theses and Dissertations

Alzheimer's disease is characterized by the presence of amyloid plaques, made up primarily of Aϐ peptides, and neurofibrillary tangles, containing hyperphosphorylated tau. Aϐ is generated by sequential proteolysis of the amyloid precursor protein (APP) by beta and gamma secretases. The leading hypothesis of Alzheimer's disease pathogenesis is the amyloid cascade hypothesis, which suggests that amyloid is central to the disease process. However, tau pathology correlates more closely with cognitive dysfunction and follows a predictable anatomical course through the brain. We hypothesize that if Aϐ is upstream of tau pathology and tau pathology follows this predictable course through the brain, Aϐ …

Discovery Of New Biomarkers Of Mild Cognitive Impairment And Alzheimer's Disease Risk In Buccal Cells Using Laser Scanning Cytometry, Maxime Francois

Theses: Doctorates and Masters

Previous studies have shown that mild cognitive impairment (MCI) may reflect the early stages of more pronounced neurodegenerative disorders such as Alzheimer’s disease (AD). In clinical practice, patients with AD are not usually identified until the disease has progressed to a stage when primary prevention is no longer possible. Therefore there is a need for a minimally invasive and inexpensive diagnostic to identify those who exhibit cellular pathology indicative of MCI and AD risk so that they can be prioritised for primary prevention. Human buccal cells are accessible in a minimally invasive manner, and exhibit cytological and nuclear morphologies that …

Multiple Subject Barycentric Discriminant Analysis (Musubada): How To Assign Scans To Categories Without Using Spatial Normalization, Hervé Abdi, Lynne J. Williams, Andrew C. Connolly, M. Ida Gobbini

Dartmouth Scholarship

We present a new discriminant analysis (DA) method called Multiple Subject Barycentric Discriminant Analysis (MUSUBADA) suited for analyzing fMRI data because it handles datasets with multiple participants that each provides different number of variables (i.e., voxels) that are themselves grouped into regions of interest (ROIs). Like DA, MUSUBADA (1) assigns observations to predefined categories, (2) gives factorial maps displaying observations and categories, and (3) optimally assigns observations to categories. MUSUBADA handles cases with more variables than observations and can project portions of the data table (e.g., subtables, which can represent participants or ROIs) on the factorial maps. Therefore MUSUBADA can …