Life Sciences Commons^™

A Customized Quantitative Pcr Microrna Panel Provides A Technically Robust Context For Studying Neurodegenerative Disease Biomarkers And Indicates A High Correlation Between Cerebrospinal Fluid And Choroid Plexus Microrna Expression, Wang-Xia Wang, David W. Fardo, Gregory A. Jicha, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

MicroRNA (miRNA) expression varies in association with different tissue types and in diseases. Having been found in body fluids including blood and cerebrospinal fluid (CSF), miRNAs constitute potential biomarkers. CSF miRNAs have been proposed as biomarkers for neurodegenerative diseases; however, there is a lack of consensus about the best candidate miRNA biomarkers and there has been variability in results from different research centers, perhaps due to technical factors. Here, we sought to optimize technical parameters for CSF miRNA studies. We examined different RNA isolation methods and performed miRNA expression profiling with TaqMan® miRNA Arrays. More specifically, we developed a customized …

Brain Energy Homeostasis And The Regulation Of N-Acetyl-Aspartate Metabolism In Development And Disease, Samantha Zaroff

Graduate School of Biomedical Sciences Theses and Dissertations

N-acetylaspartate (NAA) is a non-invasive clinical marker of neuronal metabolic integrity because of its strong proton magnetic resonance spectroscopy (H-MRS) peak and direct correlation with energetic integrity. Specifically, NAA is used to track the progression of neurodegenerative diseases due to the characteristic reduction of whole brain levels of NAA which occur simultaneously with reduced glucose utilization and mitochondrial dysfunction, but prior to the onset of disease specific pathology. However, NAA will also significantly increase simultaneously with energetic integrity during periods of recovery or remission in applicable disorders, such as traumatic brain injuries. Unfortunately, it remains enigmatic exactly why NAA is …

Low Arousal Positive Emotional Stimuli Attenuate Aberrant Working Memory Processing In Persons With Mild Cognitive Impairment, Lucas S. Broster, Shonna L. Jenkins, Sarah D. Holmes, Gregory A. Jicha, Yang Jiang

Behavioral Science Faculty Publications

Emotional enhancement effects on memory have been reported to mitigate the pathophysiology of Alzheimer’s disease (AD). However, relative to their manifestation in persons without pathologic aging, these effects may be reduced in magnitude or even deleterious, especially in tasks that more closely model ecologic memory performance. Based upon a synthesis of such reports, we hypothesized that in persons with AD low arousal positive stimuli would evoke relatively intact emotional enhancement effects, but that high arousal negative stimuli would evoke disordered emotional enhancement effects. To assess this, participants with and without mild cognitive impairment (MCI) presumed to be due to AD …

Sex Differences In Estradiol Signaling In The Zebra Finch (Taeniopygia Gutatta) Auditory Cortex, Amanda Krentzel

Doctoral Dissertations

Although several sex differences have been described in brain structure, function, and development, sex as a biological factor is underrepresented in neuroscience studies. In the mammalian brain, there are sex differences in the mechanism of rapid estradiol actions on neuronal physiology. In the songbird, the brain is a major source of estradiol production, and estradiol rapidly modulates auditory responsiveness through dynamic changes and an unknown receptor mechanism. I set out to determine if there are sex differences in rapid estradiol modulation of auditory cortical activity, as has been shown in other systems. I tested this hypothesis through three aims: 1) …

Chronic Traumatic Encephalopathy-Integration Of Canonical Traumatic Brain Injury Secondary Injury Mechanisms With Tau Pathology, Jacqueline R. Kulbe, Edward D. Hall

Spinal Cord and Brain Injury Research Center Faculty Publications

In recent years, a new neurodegenerative tauopathy labeled Chronic Traumatic Encephalopathy (CTE), has been identified that is believed to be primarily a sequela of repeated mild traumatic brain injury (TBI), often referred to as concussion, that occurs in athletes participating in contact sports (e.g. boxing, football, football, rugby, soccer, ice hockey) or in military combatants, especially after blast-induced injuries. Since the identification of CTE, and its neuropathological finding of deposits of hyperphosphorylated tau protein, mechanistic attention has been on lumping the disorder together with various other non-traumatic neurodegenerative tauopathies. Indeed, brains from suspected CTE cases that have come to autopsy …

Targeting Mitochondrial Dysfunction In Cns Injury Using Methylene Blue; Still A Magic Bullet?, Hemendra J. Vekaria, Lora Talley Watts, Ai-Ling Lin, Patrick G. Sullivan

Spinal Cord and Brain Injury Research Center Faculty Publications

Complex, multi-factorial secondary injury cascades are initiated following traumatic brain injury, which makes this a difficult disease to treat. The secondary injury cascades following the primary mechanical tissue damage, are likely where effective therapeutic interventions may be targeted. One promising therapeutic target following brain injury are mitochondria. Mitochondria are complex organelles found within the cell, which act as powerhouses within all cells by supplying ATP. These organelles are also necessary for calcium cycling, redox signaling and play a major role in the initiation of cell death pathways. When mitochondria become dysfunctional, there is a tendency for the cell to loose …

Clinically Silent Alzheimer's And Vascular Pathologies Influence Brain Networks Supporting Executive Function In Healthy Older Adults, Brian T. Gold, Christopher A. Brown, Jonathan G. Hakun, Leslie M. Shaw, John Q. Trojanowski, Charles D. Smith

Neuroscience Faculty Publications

Aging is associated with declines in executive function. We examined how executive functional brain systems are influenced by clinically silent Alzheimer’s disease (AD) pathology and cerebral white matter hyperintensities (WMHs). Twenty-nine younger adults and thirty-four cognitively normal older adults completed a working memory paradigm while functional magnetic resonance imaging (fMRI) was performed. Older adults further underwent lumbar cerebrospinal fluid (CSF) draw for assessment of AD pathology and FLAIR imaging for assessment of WMHs. Accurate working memory performance in both age groups was associated with high fronto-visual functional connectivity (fC). However, in older adults, higher expression of fronto-visual fC was linked …

Confabulation In Individuals With Disorders Of The Corpus Callosum: Educational Implications, Cheryl Lynn Wright

Dissertations

Individuals with disorders of the corpus callosum (DCC) may have subtle cognitive differences. Historically, confabulation has been associated with DCC. Therapies to mitigate confabulation is a newly emerging field. This study explores the possible educational implications that those with DCC may experience with confabulation.

The community of people with DCC and the community of people who interact with individuals with DCC were surveyed to ascertain the prevalence of confabulation within the population of those with DCC. A subset of questions probed whether age and/or gender impact the rates of reported confabulation. The research paradigm included a section that covered the …

Gpr37l1 Modulates Seizure Susceptibility: Evidence From Mouse Studies And Analyses Of A Human Gpr37l1 Variant, Michelle M. Giddens, Jennifer C. Wong, Jason P. Schroeder, Emily G. Farrow, Brilee M. Smith, Sharon Owino, Sarah E. Soden, Rebecca C. Meyer, Carol Saunders, J. B. Lepichon, David Weinshenker, Andrew Escayg, Randy A. Hall

Neuroscience: Faculty Publications

Progressive myoclonus epilepsies (PMEs) are disorders characterized by myoclonic and generalized seizures with progressive neurological deterioration. While several genetic causes for PMEs have been identified, the underlying causes remain unknown for a substantial portion of cases. Here we describe several affected individuals from a large, consanguineous family presenting with a novel PME in which symptoms begin in adolescence and result in death by early adulthood. Whole exome analyses revealed that affected individuals have a homozygous variant in GPR37L1 (c.1047G > T [Lys349Asn]), an orphan G protein-coupled receptor (GPCR) expressed predominantly in the brain. In vitro studies demonstrated that the K349N substitution …

Impulsive Personality Dimensions Are Associated With Altered Behavioral Performance And Neural Responses In The Monetary Incentive Delay Task, Ruolei Gu, Yang Jiang, Seth Kiser, Chelsea L. Black, Lucas S. Broster, Yue-Jia Luo, Thomas H. Kelly

Behavioral Science Faculty Publications

Individual differences in dimensions of impulsivity personality including disinhibition and sensation seeking modulate approach responses to reinforcing stimuli, such as drugs and money. The current study examined the effects of monetary incentive on both behavioral performance and electrophysiological activity among individuals varying in disinhibition and sensation seeking. The monetary incentive delay (MID) task was completed under electroencephalogram (EEG) recording. Behavioral data showed that higher disinhibition and sensation-seeking were associated with lower performance accuracy. Event-related potential (ERP) data showed that high reinforcement cues elicited a larger late positive component (LPC) than other conditions among high disinhibition participants, indicating its strong emotional …

Peripheral Administration Of The Soluble Tnf Inhibitor Xpro1595 Modifies Brain Immune Cell Profiles, Decreases Beta-Amyloid Plaque Load, And Rescues Impaired Long-Term Potentiation In 5xfad Mice, Kathryn P. Macpherson, Pradoldej Sompol, George T. Kannarkat, Jianjun Chang, Lindsey Sniffen, Mary E. Wildner, Christopher M. Norris, Malú G. Tansey

Sanders-Brown Center on Aging Faculty Publications

Clinical and animal model studies have implicated inflammation and peripheral immune cell responses in the pathophysiology of Alzheimer’s disease (AD). Peripheral immune cells including T cells circulate in the cerebrospinal fluid (CSF) of healthy adults and are found in the brains of AD patients and AD rodent models. Blocking entry of peripheral macrophages into the CNS was reported to increase amyloid burden in an AD mouse model. To assess inflammation in the 5xFAD (Tg) mouse model, we first quantified central and immune cell profiles in the deep cervical lymph nodes and spleen. In the brains of Tg mice, activated (MHCII …

Transcranial Direct Current Stimulation And Sports Performance, Dylan J. Edwards, Mar Cortes, Susan Wortman-Jutt, David Putrino, Marom Bikson, Gary Thickbroom, Alvaro Pascual-Leone

Publications and Research

No abstract provided.

Major Neurotransmitters In The Brain, Amy S. Yu '17

Independent Study

Arguably the most important and powerful organ in the human body, the brain controls virtually everything one does. From chewing gum to running a marathon, the brain dictates one’s physical responses and actions, while also mediating learning, memory, and emotions. These functions are all regulated by neurotransmitter activity in the brain. While the brain works in complex ways, recent discoveries about neurotransmitters allow us to better understand the underlying mechanisms of brain operation. Each neurotransmitter fulfills a distinct role, but they rely on one another to perform certain activities in the brain as well. The purpose of this review is …

Fixation-Related Fmri And Syntactic Networks In The Brain, Brent Foster, Ben Carter, Steven Luke

FHSS Mentored Research Conference

Humans comprehend language at varying levels of complexity. Syntax, in particular, deals with the arrangement of words and phrases into meaningful sentences. For instance, in English we expect most sentences to follow some variation of the order "Subject-Verb-Object: such as "The boy (Subject) ate (Verb) cake (Object)." On the surface, such grammatical rules seem simple. However, our understanding of how the brain implements these rules to understand sentences is incomplete.

Syntax appears to be associated with Broca's area in the frontal lobe and various regions of the left temporal lobe. However, recent research has provided controversial data suggesting that the …

Notes On Human Trials Of Transcranial Direct Current Stimulation Between 1960 And 1998, Zeinab Esmaeilpour, Pedro Schestatsky, Marom Bikson, André R. Brunoni, Ada Pellegrinelli, Fernanda X. Piovesan, Mariana M. S. A. Santos, Renata B. Menezes, Felipe Fregni

Publications and Research

Background: Transcranial direct current stimulation (tDCS) is investigated to modulate neuronal function including cognitive neuroscience and neuropsychiatric therapies. While cases of human stimulation with rudimentary batteries date back more than 200 years, clinical trials with current controlled stimulation were published intermittently since the 1960s. The modern era of tDCS only started after 1998.

Objectives: To review methods and outcomes of tDCS studies from old literature (between 1960 and 1998) with intention of providing new insight for ongoing tDCS trials and development of tDCS protocols especially for the purpose of treatment.

Methods: Articles were identified through a search …

Calcium's Role As Nuanced Modulator Of Cellular Physiology In The Brain, Hilaree N. Frazier, Shaniya Maimaiti, Katie L. Anderson, Lawrence D. Brewer, John C. Gant, Nada M. Porter, Olivier Thibault

Pharmacology and Nutritional Sciences Faculty Publications

Neuroscientists studying normal brain aging, spinal cord injury, Alzheimer’s disease (AD) and other neurodegenerative diseases have focused considerable effort on carefully characterizing intracellular perturbations in calcium dynamics or levels. At the cellular level, calcium is known for controlling life and death and orchestrating most events in between. For many years, intracellular calcium has been recognized as an essential ion associated with nearly all cellular functions from cell growth to degeneration. Often the emphasis is on the negative impact of calcium dysregulation and the typical worse-case-scenario leading inevitably to cell death. However, even high amplitude calcium transients, when executed acutely can …

How Should Justice Policy Treat Young Offenders?, B J. Casey, Richard J. Bonnie, Andre Davis, David L. Faigman, Morris B. Hoffman, Owen D. Jones, Read Montague, Stephen J. Morse, Marcus E. Raichle, Jennifer A. Richeson, Elizabeth S. Scott, Laurence Steinberg, Kim A. Taylor-Thompson, Anthony D. Wagner

All Faculty Scholarship

The justice system in the United States has long recognized that juvenile offenders are not the same as adults, and has tried to incorporate those differences into law and policy. But only in recent decades have behavioral scientists and neuroscientists, along with policymakers, looked rigorously at developmental differences, seeking answers to two overarching questions: Are young offenders, purely by virtue of their immaturity, different from older individuals who commit crimes? And, if they are, how should justice policy take this into account?

A growing body of research on adolescent development now confirms that teenagers are indeed inherently different from adults, …

Animal Models, Agendas And Sentience, Thomas Creson

Animal Sentience

Woodruff’s target article on teleost consciousness is a well-organized logical argument for considering the fish as a sentient being. This becomes more important for animal ethical discussion as the fish becomes a more important and legitimate animal model for investigating animal states and traits associated with higher levels of behavior such as learning and memory.

The Emotional Brain Of Fish, Sonia Rey Planellas

Animal Sentience

Woodruff (2017) analyzes structural homologies and functional equivalences between the brains of mammals and fish to understand where sentience and social cognition might reside in teleosts. He compares neuroanatomical, neurophysiological and behavioural correlates. I discuss current advances in the study of fish cognitive abilities and emotions, and advocate an evolutionary approach to the underlying basis of sentience in teleosts.

Aβ Vaccination In Combination With Behavioral Enrichment In Aged Beagles: Effects On Cognition, Aβ, And Microhemorrhages, Paulina R. Davis, Ginevra Giannini, Karin Rudolph, Nathaniel Calloway, Christopher M. Royer, Tina L. Beckett, M. Paul Murphy, Frederick Bresch, Dieter Pagani, Thomas Platt, Xiaohong Wang, Amy Skinner Donovan, Tiffany L. Sudduth, Wenjie Lou, Erin L. Abner, Richard J. Kryscio, Donna M. Wilcock, Edward G. Barrett, Elizabeth Head

Sanders-Brown Center on Aging Faculty Publications

Beta-amyloid (Aβ) immunotherapy is a promising intervention to slow Alzheimer’s disease (AD). Aging dogs naturally accumulate Aβ and show cognitive decline. An active vaccine against fibrillar Aβ 1–42 (VAC) in aged beagles resulted in maintenance but not improvement of cognition along with reduced brain Aβ. Behavioral enrichment (ENR) led to cognitive benefits but no reduction in Aβ. We hypothesized cognitive outcomes could be improved by combining VAC with ENR in aged dogs. Aged dogs (11–12 years) were placed into 4 groups: (1) control/control (C/C); (2) control/VAC (C/V); (3) ENR/control (E/C); (4) ENR and VAC (E/V) and treated for 20 months. …

Harnessing Electrocorticographic Signals For Neuroscience And Neurosurgery, Adriana De Pesters

Legacy Theses & Dissertations (2009 - 2024)

Daily human activities, such as speaking, driving or listening to music, are produced by activations of neurons in the brain. Where, when and how these activations occur has been the subject of intense debate for the last decades. Traditional techniques to image the human brain, such as functional magnetic resonance imaging (fMRI) or electroencephalography (EEG), only provide limited information regarding where and when these activations take place. For that reason, critical information is currently missing regarding how neurons from different parts of the brain interact and coordinate their activity to implement behavior. This information is critical to understand human behavior …

Widespread Tau Seeding Activity At Early Braak Stages, Jennifer L. Furman, Jaime Vaquer-Alicea, Charles L. White, Nigel J. Cairns, Peter T. Nelson, Marc I. Diamond

Pathology and Laboratory Medicine Faculty Publications

Transcellular propagation of tau aggregates may underlie the progression of pathology in Alzheimer's disease (AD) and other tauopathies. Braak staging (B1, B2, B3) is based on phospho-tau accumulation within connected brain regions: entorhinal cortex (B1); hippocampus/limbic system (B2); and frontal and parietal lobes (B3). We previously developed a specific and sensitive assay that uses flow cytometry to quantify tissue seeding activity based on fluorescence resonance energy transfer (FRET) in cells that stably express tau reporter proteins. In a tauopathy mouse model, we have detected seeding activity far in advance of histopathological changes. It remains unknown whether individuals with AD also …