Neurosciences Commons^™

Preclinical Targeting Of Trem2 For The Treatment Of Alzheimer's Disease-Type Pathology In A Transgenic Mouse Model, Brittani Rae Price

Theses and Dissertations--Physiology

Alzheimer's disease (AD) is defined as a progressive neurodegenerative disorder and is characterized by a devastating mental decline. There are three pathological hallmarks of the disease necessary for its diagnosis, these are extracellular amyloid plaques comprised of the beta-amyloid (Aβ) protein, intracellular neurofibrillary tangles comprised of hyperphosphorylated tau protein, and marked neuronal loss. Active immunization against Aβ_1-42 or passive immunization with monoclonal anti-Aβ antibodies has been shown to reduce amyloid deposition and improve cognition in transgenic mouse models of AD, aged beagles, and nonhuman primates. Unfortunately, due to cerebrovascular adverse events, both active and passive immunization strategies targeting Aβ …

Decrease In P3-Alcb37 And P3-Alcb40, Products Of Alcadein B Generated By G-Secretase Cleavages, In Aged Monkeys And Patients With Alzheimer’S Disease, Saori Hata, Chiori Omori, Ayano Kimura, Haruka Saito, Nobuyuki Kimura, Veer Gupta, Steve Pedrini, Eugene Hone, Pratishtha Chatterjee, Kevin Taddei, Kensaku Kasuga, Takeshi Ikeuchi, Masaaki Waragai, Masaki Nishimura, Anqi Hu, Tadashi Nakaya, Laurent Meijer, Masahiro Maeda, Tohru Yamamoto, Colin L. Masters, Chris C. Rowe, David Ames, Kazuo Yamamoto, Ralph N. Martins, Sam Gandy, Toshiharu Suzuki

Research outputs 2014 to 2021

Introduction Neuronal p3-Alcβ peptides are generated from the precursor protein Alcadein β (Alcβ) through cleavage by α- and γ-secretases of the amyloid β (Aβ) protein precursor (APP). To reveal whether p3-Alcβ is involved in Alzheimer's disease (AD) contributes for the development of novel therapy and/or drug targets. Methods We developed new sandwich enzyme-linked immunosorbent assay (sELISA) systems to quantitate levels of p3-Alcβ in the cerebrospinal fluid (CSF). Results In monkeys, CSF p3-Alcβ decreases with age, and the aging is also accompanied by decreased brain expression of Alcβ. In humans, CSF p3-Alcβ levels decrease to a greater extent in those with …

The Impact Of Post Translational Modification On The Aggregation Of The Ss-Amyloid Peptide In The Presence Or Absence Of Lipids, Albert Walton Pilkington Iv

Graduate Theses, Dissertations, and Problem Reports (ETD)

Alzheimer’s disease (AD) is a neurodegenerative condition afflicting 5.7 million Americans with no effective treatments. The pathology of AD is described by the formation of neurotoxic oligomers formed by the self-assembly of amyloid-β (Aβ). The affinity of oligomers for cellular membranes disrupts calcium homeostasis and is believed to be the underlying cause of neurotoxicity; however, due to the metastability of oligomers, it has been difficult to understand their role in membrane interactions and self-assembly. Here we utilize post translational modifications (PTM) to understand the role of specific amino acids on Aβ₄₀-membrane interactions and self-assembly. We employ ThT, AFM, …

Mice, Acorns, And Lyme Disease: A Case Study To Teach The Ecology Of Emerging Infectious Diseases, Laurieann Klockow

Biomedical Sciences Faculty Research and Publications

Ebola, Zika, the recall of contaminated lettuce - these are just a few recent outbreaks making headlines. Students should be able to connect what they learn in their biology courses to explain these events happening around them. Unfortunately, students do not necessarily make those connections. Therefore, it is important, as instructors, to provide opportunities where students engage with societal issues and problems related to course content and case studies, using headlines from the news are one way to do this.

Here I describe a case study about Lyme disease that engages students in learning about the ecology of infectious disease. …

Development Of More Light Sensitive And Red-Shifted Channelrhodopsin Variants For Optogenetic Vision Restoration, Tushar Harishkumar Ganjawala

Wayne State University Dissertations

Discovery of channelrhodopsin (ChR), a light sensitive protein from green algae, has revolutionized the field of neuroscience research by empowering scientist to control neuron through the light, the technology popularly known as optogenetics. The ChR based optogenetics is one of the promising approaches for treating blindness caused by photoreceptor degenerative diseases such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD). Fundamentally, the approach is about imparting light sensitivity to surviving inner retinal cells by ectopic expression of genetically encoded light sensitive proteins, such as ChR2. Although the concept of optogenetic approach has been proved by using ChR2, a major …

Stress-Dependent Regulation Of A Major Node Of The Insulin-Like Peptide Network That Modulates Survival, Rashmi Chandra

Wayne State University Dissertations

Chronic stress disrupts insulin signaling, predisposing human populations to diabetes, cardiovascular disease, Alzheimer’s Disease, and other metabolic and neurological disorders, including post-traumatic disorders (PTSD). Thus, efficient recovery from stress optimizes survival. However, stress recovery in humans is difficult to study, but is much easier to dissect in model organisms. The worm genetic model Caenorhabditis elegans can switch between stressed and non-stressed states, and this switch is largely regulated by insulin signaling. Previously, the Alcedo lab proposed that insulin-like peptides (ILPs), which exist as multiple members of a protein family in both C. elegans and humans, implements a combinatorial coding strategy …

Translational Modeling Of Non-Invasive Electrical Stimulation, Dennis Quangvinh Truong

Dissertations and Theses

Seminal work in the early 2000’s demonstrated the effect of low amplitude non-invasive electrical stimulation in people using neurophysiological measures (motor evoked potentials, MEPs). Clinical applications of transcranial Direct Current Stimulation (tDCS) have since proliferated, though the mechanisms are not fully understood. Efforts to refine the technique to improve results are on-going as are mechanistic studies both in vivo and in vitro. Volume conduction models are being applied to these areas of research, especially in the design and analysis of clinical montages. However, additional research on the parameterization of models remains.

In this dissertation, Finite Element Method (FEM) models of …

Using Fundamental Properties Of Light To Investigate Photonic Effects In Condensed Matter And Biological Tissues, Laura A. Sordillo

Dissertations and Theses

Light possesses characteristics such as polarization, wavelength and coherence. The interaction of light and matter, whether in a semiconductor or in a biological sample, can reveal important information about the internal properties of a system. My thesis focuses on two areas: photocarriers in gallium arsenide and biomedical optics. Varying the excitation wavelength can be used to study both biological tissue and condensed matter. I altered the excitation wavelengths to be in the longer near-infrared (NIR) optical windows, in the shortwave infrared (SWIR) range, a wavelength region previously thought to be unusable for medical imaging. With this method, I acquired high …

Studies Of Oxidative Damage, Brain Proteome, And Neurochemical Metabolites In Cognitive And Neurodegenerative Disorders: (1) Chemotherapy-Induced Cognitive Impairment; (2) Parkinson Disease Rat Model, Xiaojia Ren

Theses and Dissertations--Chemistry

The rate of cancer patients is increasing as the development of science and technology. Twenty million cancer survivors are estimated living in the United States by 2025. However, many cancer survivors show cognitive dysfunction, negatively affecting the quality of life. These cognitive impairments are recognized as chemotherapy-induced cognitive impairment (CICI), also called "chemo brain" by cancer survivors, including the diminished ability of memory and learning, hard to concentrate and focus, as well as diminution of executive function and processing speed. The etiologies and pathologies of CICI are complicated, especially in most cases the anti-cancer drug cannot cross the blood-brain barrier …

Investigating The Effects Of Methylphenidate On Cue Salience And Behavioral Flexibility: Role Of D2 Receptors, Mercedes Mcwaters

Graduate Research Theses & Dissertations

Healthy individuals worldwide are using cognitive enhancing drugs in an attempt to remain competitive in society for education, careers, and athletics. Commonly, these individuals are using prescription stimulants, such as methylphenidate (MPH), due to their known acute neuroenhancing effects. While these neuroenhancing effects have been established using a variety of learning, memory, and attention tasks in humans and rodents, little research has investigated the effects of MPH use on specific components of these tasks, such as cue salience. One process that is important for learning the relationship between a cue and a reward is salience, or the heightened perception and …

Determinants Of Occupational Injuries Among Building Construction Workers In Kampala City, Uganda, Arthur Kiconco, Nathan Ruhinda, Abdullah Ali Halage, Stephen Watya, William Bazeyo, John C. Ssempebwa, Joseph Byonanebye

Biomedical Sciences Faculty Research and Publications

Background

Globally, about 1000 people die and close to 860,000 people sustain injury at work daily. Injury prevention and control require contextual evidence, although most studies in Uganda have focused on general causes. Factors associated with occupational injuries among building construction workers were assessed in this study.

Methods

A cross-sectional study among building construction workers was conducted in Kampala, Uganda. A standardized semi-structured questionnaire was used to collect data. Three hundred nineteen (319) participants were randomly and proportionately selected from 57 construction sites. Descriptive statistics were used to describe the variables while generalized linear modeling was used to estimate the …

When Brain Stimulation Backfires, Sarah Beth Bell

Theses and Dissertations--Psychology

tDCS brain stimulation does not always work in the intended direction. It has been found to sometimes worsen behavior rather than improve it. A preliminary study shows that people high on sensation-seeking and lack of premeditation were prone to reverse effects of tDCS on performance on a Stop Signal Task. Both of these constructs are related to dopamine levels. Study 2 seeks to intentionally cause a reverse effect of tDCS by increasing participants’ dopamine levels via caffeine. There was not a significant interaction between tDCS and caffeine on errors on the Stop Signal Task in this study. However, other factors …

A High Fructose Diet Alters Affective-Like Behavior And Metrics Of Synaptic Mitochondrial Function Differentially In Male And Female Rats, Alix H. Kloster

Theses and Dissertations

Fructose consumption has become a normalized part of the standard American diet over the past 40 years. While fructose consumption is a known risk factor of metabolic syndrome, there is increasing evidence that fructose consumption influences brain and behavior. Recently, more interest has been focused on mitochondrial dysfunction as a potential link between metabolic stress and modifications of the central nervous system. Mitochondria are in the unique position of both regulating and being vulnerable to alterations in energy homeostasis. Sex-differences are well categorized in the presentation of metabolic symptoms associated with excessive fructose consumption. Thus, it is important to characterize …

Thermal Block Of Action Potentials Is Primarily Due To Voltage-Dependent Potassium Currents: A Modeling Study, Michael W. Jenkins, Hillel J. Chiel

Faculty Scholarship

Objective. Thermal block of action potential conduction using infrared lasers is a new modality for manipulating neural activity. It could be used for analysis of the nervous system and for therapeutic applications. We sought to understand the mechanisms of thermal block. Approach. To analyze the mechanisms of thermal block, we studied both the original Hodgkin/Huxley model, and a version modified to more accurately match experimental data on thermal responses in the squid giant axon. Main results. Both the original and modified models suggested that thermal block, especially at higher temperatures, is primarily due to a depolarization-activated hyperpolarization as increased temperature …

Soft-Surface Grasping: Radular Opening In Aplysia Californica, Catherine E. Kehl, Joey Wu, Sisi Lu, Richard F. Drushel, Rebekah K. Smoldt, Hillel J. Chiel

Faculty Scholarship

Grasping soft, irregular material is challenging both for animals and robots. The feeding systems of many animals have adapted to this challenge. In particular, the feeding system of the marine mollusk Aplysia californica, a generalist herbivore, allows it to grasp and ingest seaweeds of varying shape, texture and toughness. On the surface of the grasper of A. californica is a structure known as the radula, a thin flexible cartilaginous sheet with fine teeth. Previous in vitro studies suggested that intrinsic muscles, I7, are responsible for opening the radula. Lesioning I7 in vivo does not prevent animals from grasping and ingesting …

Targeting The Blood-Brain Barrier To Prevent Sepsis-Associated Cognitive Impairment, Divine C. Nwafor, Allison L. Brichacek, Afroz S. Mohammad, Jessica Griffith, Brandon P. Lucke-Wold, Stanley A. Benkovic, Werner J. Geldenhuys, Paul R. Lockman, Candice M. Brown

Faculty & Staff Scholarship

Sepsis is a systemic inflammatory disease resulting from an infection. This disorder affects 750 000 people annually in the United States and has a 62% rehospitalization rate. Septic symptoms range from typical flu-like symptoms (eg, headache, fever) to a multifactorial syndrome known as sepsis-associated encephalopathy (SAE). Patients with SAE exhibit an acute altered mental status and often have higher mortality and morbidity. In addition, many sepsis survivors are also burdened with long-term cognitive impairment. The mechanisms through which sepsis initiates SAE and promotes long-term cognitive impairment in septic survivors are poorly understood. Due to its unique role as an interface …

A Biomimetic Approach To Controlling Restorative Robotics, Matthew T. Boots

Graduate Theses, Dissertations, and Problem Reports (ETD)

Movement is the only way a person can interact with the world around them. When trauma to the neuromuscular systems disrupts the control of movement, quality of life suffers. To restore limb functionality, active robotic interventions and/or rehabilitation are required. Unfortunately, the primary obstacle in a person’s recovery is the limited robustness of the human-machine interfaces. Current systems rely on control approaches that rely on the person to learn how the system works instead of the system being more intuitive and working with the person naturally. My research goal is to design intuitive control mechanisms based on biological processes termed …

A Computational Study Of Sleep And The Hemispheres Of The Brain, Tera Ashley Glaze

Doctoral Dissertations

"Sleep and sleep cycles have been studied for over a century, and scientists have worked on modeling sleep for nearly as long as computers have existed. Despite this extensive study, sleep still holds many mysteries. Larger and more extensive sleep-wake models have been developed, and the circadian drive has been depicted in numerous fashions, as well as incorporated into scores of studies. With the ever-growing knowledge of sleep comes the need to find more ways to examine, quantify, and define it in the context of the most complex part of the human anatomy -- the brain. Presented here is the …