Neuroscience and Neurobiology Commons^™

Testosterone Administration In Premenopausal Women, Kaeli Nichol Shockley

Graduate Student Theses, Dissertations, & Professional Papers

Testosterone administration is a relatively uncommon practice in the United States. Women are at risk of having health issues that could be remedied by low-dose testosterone administration via transdermal patch or topical cream. This paper explores the potential health and wellness benefits of administering low-dose testosterone to premenopausal women. Low-dose Testosterone may improve depression scores as well as upregulate markers of bone formation in women with anorexia nervosa. Higher testosterone was associated with increased muscle mass and muscular strength in collegiate female athletes. Testosterone given at lower doses increases muscle mass and exercise performance in college-age women. Overall, testosterone supplementation …

Prospective Associations Of Fish Consumption In Cognitive Function And Depressive Symptoms Among Puerto Rican Adults, Johanna Grace Koroma

Honors Theses and Capstones

Johanna Koroma, Anne Bodenrader, and Sherman Bigornia

Objectives

Fish intake has been linked to certain neural benefits, specifically in slowing cognitive decline and attenuating depressive symptoms. However, existing evidence is conflicting and insufficient. The present study aimed to investigate the association of fish consumption with depressive symptoms and cognitive function among Puerto Rican adults.

Methods

Data is acquired from the Boston Puerto Rican Health Study, comprised of 1517 adults residing in the Boston Metro Area. Dietary patterns were evaluated using a validated food frequency questionnaire (FFQ) with follow-up surveys conducted 2 years from baseline. Consumption was organized into quartiles based …

The Biobehavioral Effects Of Embryonic Exposure To Neural Inflammation And Oxidative Stress In Zebrafish, Dalton J. Anderson

Honors College Theses

The purpose of this research is to improve understanding of the neurodevelopmental effects of embryonic exposure to elevated inflammation and oxidative stress induced by the antipyretic drug acetaminophen (APAP). Our study was the first to examine the interactive effects of APAP and inflammation in zebrafish embryos and how the treatments affect brain development and larval behavior. Experimental groups of zebrafish larvae were exposed to lipopolysaccharide (LPS) to induce inflammation, APAP, or LPS + APAP and larval behavior was analyzed using Ethovision automated behavioral tracking software. We also measured changes in whole-brain Glycogen Synthase Kinase 3 Beta (GSK3B) and GSK3B phosphorylation, …

Effects Of Pancreatic Amylin On The Peripheral And Cns Immune Response In A Model Of Type-2 Diabetic Brain Injury, Edric Da'shon Winford

Theses and Dissertations--Neuroscience

Type-2 diabetes (T2D) is a metabolic disorder that increases the risk for cerebrovascular disease and dementia and is associated with the progression of Alzheimer's Disease; however, the mechanisms responsible for T2D-associated dementia are still poorly understood. T2D leads to alterations of the innate and adaptive immune response that contribute to its progression, but how these cells contribute to cognitive decline during T2D is unknown. As there are no approved therapeutics for T2D that modulate the immune response, it is important that we investigate how peripheral immune cells contribute to cognitive decline during T2D. Amylin is an amyloidogenic hormone synthesized and …

Caenorhabditis Elegans Rapgef Promotes Synaptic Development Through A Small G Protein Signaling Cascade, Reagan Em Lamb

Theses and Dissertations--Neuroscience

Synaptic dysfunction is a major contributor toward the development of many neurological disorders. For proper development, synapses require a series of signaling pathways to guide them, but not all the mechanisms underlying these processes are understood. Here, we used the neuromuscular junction of Caenorhabditis elegans as a model circuitry for examining underlying pathways that mediate proper development of synapses. We hypothesized that the C. elegans RapGEF2 and RapGEF6 orthologue, PXF-1, contributed toward development of cholinergic synapses at the neuromuscular junction. Using behavioral assays and fluorescence microscopy, we found that pxf-1 mutant animals had decreased neuromuscular junction function and decreased synaptic …

Characterizing Age-Associated Cd19+ B Cells After Stroke In Aged Male And Female Mice Reveals Sex-Dependent Functional Recovery, Katie Colson

Theses and Dissertations--Neuroscience

Age-Associated B cells (ABCs) are atypical memory B cells commonly expressing CD11b, CD11c, and T-bet. We hypothesized that aged female mice would have worse functional outcomes after stroke due to higher brain-localized ABCs. We identified 6 ABC subsets expressed in the brain, with higher levels in uninjured animals versus 3 weeks after stroke. Contradictory to my hypothesis, aged uninjured males with higher numbers of Classical ABCs (CD11bhighCXCR5+/CXCR5-) in the brain exhibited better motor function, though with limited differences by injury or sex for other classical ABC subsets. Rare CD11b+CXCR5+ populations from uninjured mice secreted more IFN-γ when exposed to TLR7/9 …

Genetic And Metabolic Factors Shaping Functional And Systemic Recovery Post-Spinal Cord Injury: A Focus On Apoe, Chase Taylor

Theses and Dissertations--Neuroscience

There are currently approximately 300,000 individuals living with a spinal cord injury (SCI) in the United States with an additional 17,000 injuries occurring each year. Perhaps of equal importance the median age at which an SCI occurs within the population has steadily increased since the 1970s to the 2010s from 29 years to 43 years and is still on the rise. Women, historically underrepresented in biomedical research, have also seen a slight increase in SCI incidence. This increase in age of injury onset means that more people with an SCI will be impacted by genetic factors associated with Alzheimer’s disease …

The Effects Of Diet-Induced Obesity On Cerebral Microvascular Bioenergetics, Alec Anthony Hanshew

Graduate Theses, Dissertations, and Problem Reports (ETD)

Obesity is a worldwide epidemic but is especially a concern in the United States with over 40% of the population being obese. Obesity is known to cause increased metabolic demand, systemic inflammation, peripheral vascular dysfunction, and increased levels of oxidative stress and reactive oxygen species (ROS). However, the role of obesity on cerebrovascular bioenergetic function has not been fully elucidated. This study aimed to determine the impact of diet-induced obesity on cerebrovascular bioenergetics. 72, 6-month-old C57Bl/6 male and female mice were randomized into control and HFD groups. Control mice were subjected to the feeding of standard chow (18% fat, 24% …

Investigating The Role Of Spinal Motoneuron Organization In Human Motor Control, Rachel I. Taitano

Graduate Theses, Dissertations, and Problem Reports (ETD)

Mechanisms of voluntary motor control are complex and require inputs via cortical centers, peripheral sensory systems, and spinal inputs such as central pattern generators. It is hypothesized that control is simplified via utilization of motor primitives, which may rely on structures within the spinal cord, however this remains unknown in both human and non-human primates. The goal of this dissertation is to characterize muscle activity in the upper extremity in relation to the corresponding anatomical organization of spinal motoneurons to provide insight into how primitives are both organized and activated to produce movement.

The first aim of this work was …

Aberrant Lipid Accumulation And Retinal Pigment Epithelium Dysfunction In Prcd-Deficient Mice, Sree Indrani Motipally

Graduate Theses, Dissertations, and Problem Reports (ETD)

Progressive Rod-Cone Degeneration (PRCD) is a peripheral membrane protein predominantly expressed in photoreceptor outer segment (OS) disc membranes with an unknown function. Several mutations in Prcd are implicated in Retinitis pigmentosa (RP) in humans. The most common “cysteine to tyrosine” (C2Y) mutation in Prcd leads to progressive retinal atrophy in multiple dog breeds and RP in humans. Canine models harboring the C2Y mutation in Prcd show disorganized OS structure with greatly attenuated photoreceptor OS renewal rates. Recent studies show defects in the photoreceptor nascent disc flattening in the absence of Prcd. However, it is unclear how OS discs eventually …

Cerebellar Feedback Effects On Responses To Conspecific Signals Of Different Frequencies In The Electrosensory System, Elora K. Shinn

Graduate Theses, Dissertations, and Problem Reports (ETD)

Sensory systems in animals have evolved to translate physical stimuli into neural representations that, in turn, guide behavior. Feedback is critical in these processes, allowing organisms to filter redundant information and respond effectively to relevant stimuli. In humans, for example, the cerebellar flocculus provides feedback to the vestibulo-ocular reflex to stabilize eye movements during body rotation. In bats, the feedback during echolocation helps prioritize essential signals from the environment. In weakly electric fish, cerebellar feedback helps filter out redundant low-frequency modulations caused by conspecifics, enabling them to detect prey and other relevant signals. However, the influence of cerebellar feedback on …

Target Selection And Enhancement During Attentional Tracking, Marvin R. Maechler

Dartmouth College Ph.D Dissertations

At any waking moment, we are bombarded with more sensory information than we can fully process. Attention is necessary to deal with the dynamic world we live in. One fundamental function of vision and attention is to keep track of moving objects, but what are the targets of attention during tracking?

One of the first theories of attentional tracking predicted that targets would be selected at early processing stages. By employing the double-drift illusion, which dissociates physical and perceived positions of moving objects, we investigated which of these positions is selected for tracking. Contrary to earlier theories and in line …

Measuring Spontaneous Neurotransmission Using Genetically Encoded Fluorescent Indicators, Amelia Jane Ralowicz

Dartmouth College Ph.D Dissertations

Synaptic connections throughout the nervous system exhibit two forms of neurotransmitter release caused by synaptic vesicle fusion, evoked and spontaneous release. Despite being discovered 70 years ago, the mechanisms governing spontaneous release have remained elusive. Our understanding of spontaneous release lacks mechanistic details including discrepancies in the sources of synaptic vesicles supporting it, the source(s) of calcium supporting it, and most importantly an unclear relationship (cooperative or antagonistic) with evoked release. These gaps exist due to a lack of experimental methods specific to the study of spontaneous release at individual synapses.

This thesis addresses these gaps in two ways. Firstly, …

Biogenesis And Function Of Microglial Extracellular Vesicles In Neuroinflammation And Parkinson’S Disease, Karl E. Biggs

Dartmouth College Ph.D Dissertations

Microglia are subject to chronic proteinaceous and environmental stress during the progression of prevalent neurodegenerative diseases such as Parkinson’s Disease (PD). Chronic stress can activate the NLR family pyrin domain containing 3 (NLRP3) pattern recognition receptor resulting in the formation of the NLRP3 inflammasome, proinflammatory signaling, and pyroptotic cell death. A distinct subset of extracellular vesicles (EVs) are released from cells upon NLRP3 activation. We studied WT and Nlrp3^-/- primary microglia exposed to bacterial stimulating agents and alpha synuclein preformed fibrils (αsyn PFFs), which model Parkinson’s disease and associated synucleinopathies. We identified the NLRP3-dependent release of the endosome fate …

Utilizing Ai Integrated Neuroimaging Technology To Expand Upon Machine Learning In Positron Emission Tomography Technology With The Aim Of Detecting Amyloid Beta Biomarkers Early In The Onset Of Alzheimer's., Ethan S. Terman

Undergraduate Research Posters

Early intervention in Alzheimer's is vital for treatment. The earlier a professional can detect symptoms and make a diagnosis the earlier a prognosis can be implemented. With the prevalence of data in our day-to-day world combined with Artificial intelligence (AI), utilizing both for machine learning can pave the way for more accurate and efficient detection of Alzheimer's and other neurodegenerative diseases. AI combined with Machine learning (ML) increases diagnostic efficiency and reduces human errors, making it a valuable resource for physicians and clinicians alike. With the increasing amount of data processing and image interpretation required, the ability to use AI …

Synaptic Zinc Transporters Support Normal Synapse Structure And Function In Mouse Auditory Cortex, Abbey Manning

Graduate Theses, Dissertations, and Problem Reports (ETD)

Many regions of the brain are highly enriched with free zinc inside glutamatergic vesicles at presynaptic terminals. At these synapses, zinc transporter 3 (ZnT3) moves zinc into vesicles where it is co-released with glutamate. Alterations in ZnT3 are implicated in multiple neurodevelopmental disorders, and ZnT3 knock-out (KO) mice – which lack synaptic zinc – show behavioral deficits associated with autism spectrum disorder and schizophrenia. Shank3 is a synaptic scaffolding protein that assists in tethering and organizing structural proteins and glutamatergic receptors in the postsynaptic density of excitatory synapses. The localization of Shank3 at excitatory synapses and the formation of stable …

Changes In Flanker Task Performance Following High-Intensity Exercise In Endurance Athletes, Felix E. Cottet-Puinel

Dissertations, Master's Theses and Master's Reports

Executive function performance following acute aerobic exercise can be influenced by multiple variables. However, little is known about the lasting effects of these exercise-induced changes. This study aimed to determine the extent to which exercise intensity impacts executive function. 14 young endurance-trained adults (5 female, 9 male) performed an Eriksen flanker task before and immediately after running high-intensity until failure and isochronal moderate-intensity (~12 min). Pre- to post-exercise-induced changes in reaction time (ms), accuracy (%), and self-reported mental effort (1-9 rating) were analyzed by overall tasks and through tasks subsections. Results showed improvement in reaction time following high- and moderate-intensity …

Effect Of Task Constraints On Neurobiological Systems Involved In Postural Control In Individuals With And Without Chronic Ankle Instability, Yuki A. Sugimoto, Patrick O. Mckeon, Christopher K. Rhea, Carl G. Mattacola

Rehabilitation Sciences Faculty Publications

The purpose of this study is to investigate the effect of task constraints on the neurobiological systems while maintaining postural control under various sensory feedback manipulations in individuals with and without Chronic Ankle Instability (CAI). Forty-two physically active individuals, with and without CAI, were enrolled in a case-control study conducted at a biomechanics research laboratory. All participants underwent the Sensory Organization Test (SOT), which assesses individuals’ ability to integrate somatosensory, visual, and vestibular feedback to maintain postural control in double-, uninjured-, and injured-limb stances under six different conditions in which variations in the sway-referenced support surface (platform) and visual surroundings, …

Clothing Design Solutions For Children With Developmental Disabilities: A Scoping Review Protocol, Nagaveni N. Nayak, Shristi Shakya, Nachiket Gudi, Sonia Khurana, Sivakumar Gopalakrishnan, Veena Rao, Bhamini Krishna Rao

Rehabilitation Sciences Faculty Publications

Children with Developmental Disabilities (DD) often face significant challenges in performing dressing task, fundamental activities of daily living. Inability to accomplish this task independently significantly impacts participation in social and recreational activities, affecting Quality of Life (QoL). Additionally, burden on caregivers increases which in turn leads to stress and burnout. Addressing dressing-related challenges through innovative clothing designs enhances self-independence, alleviate caregiver burden, and improve QoL. However, studies published in this focused area are quite heterogeneous resulting in lack of comprehensive understanding of different clothing solutions that exist for children with DD. Therefore, this scoping review is undertaken to map clothing …

Association Of Plasma Neurofilament Light Chain With Microstructural White Matter Changes In Down Syndrome, Herminia Diana Rosas, Nathaniel David Mercaldo, Yasemin Hasimoglu, Melissa Petersen, Lydia R. Lewis, Florence Lai, David Powell, Asim Dhungana, Ali Demir, David Keater, Michael Yassa, Adam M. Brickman, Sid O'Bryant

Neuroscience Faculty Publications

INTRODUCTION: Both micro- and macrostructural white matter (WM) abnormalities, particularly those related to axonal degeneration, are associated with cognitive decline in adults with Down syndrome (DS) prior to a diagnosis of Alzheimer disease. Neurofilament light chain (NfL) is a support protein within myelinated axons released into blood following axonal damage. In this study we investigated cross-sectional relationships between WM microstructural changes as measured by diffusion tensor imaging (DTI) and plasma NfL concentration in adults with DS without dementia.

METHODS: Thirty cognitively stable (CS) adults with DS underwent diffusion-weighted MRI scanning and plasma NfL measurement. DTI measures of select WM tracts …

The Differential Proteomic Response To Ischemic Stroke In Appalachian Subjects Treated With Mechanical Thrombectomy, Christopher J. Mclouth, Benton Maglinger, Jacqueline A. Frank, Kristin J. Hazelwood, Jordan P. Harp, Will Cranford, Shivani Pahwa, David Dornbos Iii, Amanda L. Trout, Ann M. Stowe, Justin F. Fraser, Keith R. Pennypacker

Neurology Faculty Publications

Introduction The Appalachia region of North America is known to have significant health disparities, specifically, worse risk factors and outcomes for stroke. Appalachians are more likely to have comorbidities related to stroke, such as diabetes, obesity, and tobacco use, and are often less likely to have stroke interventions, such as mechanical thrombectomy (MT), for emergent large vessel occlusion (ELVO). As our Comprehensive Stroke Center directly serves stroke subjects from both Appalachian and non-Appalachian areas, inflammatory proteomic biomarkers were identified associated with stroke outcomes specific to subjects residing in Appalachia. Methods There were 81 subjects that met inclusion criteria for this …

The Physiological And Behavioral Effects Of A Centrally Administered Oxytocin Receptor Antagonist On Maternal Buffering In Infant Guinea Pigs, Kendra A. Carter

Browse all Theses and Dissertations

This study investigates the role of endogenous oxytocin (OT) in maternal buffering of infant stress responses in guinea pigs. Infants received intracerebroventricular infusion of an oxytocin receptor antagonist (OTA) or artificial cerebrospinal fluid (aCSF) immediately before being placed with the mother in a novel environment for 60 minutes. Blood cortisol levels and behavioral responses, including vocalizations and crouching, were measured throughout the testing period. Results indicate only a significant effect of time, with cortisol levels increasing with time spent in the novel environment. Otherwise, no significant differences were observed either physiologically or behaviorally between aCSF and OTA conditions. This study …

Detecting Cognitive Decline In High-Functioning Older Adults: The Relationship Between Subjective Cognitive Concerns, Frequency Of High Neuropsychological Test Scores, And The Frontoparietal Control Network, Justin E. Karr, Jonathan G. Hakun, Daniel B. Elbich, Cristina N. Pinheiro, Frederick A. Schmitt

Neurology Faculty Publications

Objective: Neuropsychologists have difficulty detecting cognitive decline in high-functioning older adults because greater neurological change must occur before cognitive performances are low enough to indicate decline or impairment. For high-functioning older adults, early neurological changes may correspond with subjective cognitive concerns and an absence of high scores. This study compared high- functioning older adults with and without subjective cognitive concerns, hypothesizing those with cognitive concerns would have fewer high scores on neuropsychological testing and lower frontoparietal network volume, thickness, and connectivity.

Method: Participants had high estimated premorbid functioning (e.g., estimated intelligence ≥75th percentile or college-educated) and were divided based on …

Impact Of Amyloid And Cardiometabolic Risk Factors On Prognostic Capacity Of Plasma Neurofilament Light Chain For Neurodegeneration, Keun You Kim, Eosu Kim, Jun-Young Lee, Alzheimer’S Disease Neuroimaging Initiative

Neurology Faculty Publications

Background Plasma neurofilament light chain (NfL) is a blood biomarker of neurodegeneration, including Alzheimer’s disease. However, its usefulness may be influenced by common conditions in older adults, including amyloid‑β (Aβ) deposition and cardiometabolic risk factors like hypertension, diabetes mellitus (DM), impaired kidney function, and obesity. This longitudinal observational study using the Alzheimer’s Disease Neuroimaging Initiative cohort investigated how these conditions influence the prognostic capacity of plasma NfL. Methods Non‑demented participants (cognitively unimpaired or mild cognitive impairment) underwent repeated assessments including the Alzheimer’s Disease Assessment Scale‑Cognitive subscale (ADAS‑Cog) scores, hippocampal volumes, and white matter hyperintensity (WMH) volumes at 6‑ or 12‑month …

Astrocytic Stress Response Is Induced By Exposure To Astrocyte-Binding Antibodies Expressed By Plasmablasts From Pediatric Patients With Acute Transverse Myelitis, Chad Smith, Kiel M. Telesford, Sara G. M. Piccirillo, Yamhilette Licon‑Munoz, Wei Zhang, Key M. Tse, Jacqueline R. Rivas, Chaitanya Joshi, Dilan S. Shah, Angela X. Wu, Ritu Trivedi, Scott Christley, Yu Qian, Lindsay G. Cowell, Richard H. Scheuermann, Ann M. Stowe, Linda Nguyen, Benjamin M. Greenberg, Nancy L. Monson

Neurology Faculty Publications

Background Pediatric acute transverse myelitis (ATM) accounts for 20–30% of children presenting with a first acquired demyelinating syndrome (ADS) and may be the first clinical presentation of a relapsing ADS such as multiple sclerosis (MS). B cells have been strongly implicated in the pathogenesis of adult MS. However, little is known about B cells in pediatric MS, and even less so in pediatric ATM. Our lab previously showed that plasmablasts (PB), the earliest B cell subtype producing antibody, are expanded in adult ATM, and that these PBs produce self‑reactive antibodies that target neurons. The goal of this study was to …

Sources And Termination Patterns Of Cholinergic Input To The Ventral Nucleus Of The Lateral Lemniscus, Emily Echols

Williams Honors College, Honors Research Projects

Neurons transmit signals through an electrochemical reaction: synapses on dendrites and the cell body receive neurotransmitters, and their effect on the cell determines the signal the cell will transmit. From dendrites to axon and then to another cell at a synaptic cleft, signals can propagate, enhance each other, or inhibit other transmissions until the message is received by the target area. Understanding the science behind neural signaling and structural function begins at the level of the synapse. The neurotransmitter acetylcholine (ACh) plays a substantial role in modulating neural activity in the auditory system, but for many brainstem nuclei the source …

Zebrafish Electroretinogram Responses, Brooke Campbell

Williams Honors College, Honors Research Projects

The goal of this project is to be able to streamline a protocol for conducting ERGs on zebrafish from mice ERG protocol already present in Dr. Renna’s lab. The objective is to create a protocol specifically for zebrafish and to eliminate any issues that occur when transiting from a mice ERG protocol to a zebrafish ERG protocol and to obtain a light response from zebrafish retinae in differing light intensities. Dr. Renna’s lab has designed an Ex Vivo ERG system with less electrical interference creating defined electrical responses from mouse retina. The setup allows for continual perfusion of the retinal …

Regulation Of Er To Golgi Transport By Alg-2 And Peflin In Response To Calcium Signaling, And A Review Of Relevant Genetically-Encoded Fluorescent Tools, Danette M. Kowal Seiler

Graduate Student Theses, Dissertations, & Professional Papers

The endoplasmic reticulum performs multiple functions in the eurkaryotic cell: biomolecule synthesis, protein folding, cargo sorting and secretion, and helping to maintain cellular calcium homeostasis. Though much has been discovered about these processes and the myriad proteins, enzymes, transcription factors, ions and other factors that play their own parts, much is still left to learn. To facilitate continued study of ER-to-Golgi transport, an array of genetically-encoded fluorescent tools are available to researchers. The featured review in Chapter 1 details the history of these tools and highlights some of the newest, which also incorporate information from the fields of synthetic chemistry …

Different Cohort, Disparate Results: Selection Bias Is A Key Factor In Autopsy Cohorts, Kathryn Gauthreaux, Walter A. Kukull, Karin B. Nelson, Charles Mock, Yen-Chi Chen, Kwun C. G. Chan, David W. Fardo, Yuriko Katsumata, Erin L. Abner, Peter T. Nelson

Neurology Faculty Publications

INTRODUCTION: Research-oriented autopsy cohorts provide critical insights into dementia pathobiology. However, different studies sometimes report disparate findings, partially because each study has its own recruitment biases. We hypothesized that a straightforward metric, related to the percentage of research volunteers cognitively normal at recruitment, would predict other inter-cohort differences.

METHODS: The National Alzheimer’s Coordinating Center (NACC) provided data on N = 7178 autopsied participants from 28 individual research centers. Research cohorts were grouped based on the proportion of participants with normal cognition at initial clinical visit.

RESULTS: Cohorts with more participants who were cognitively normal at recruitment contained more individuals who …

Effects Of Energy Drink Additives On Crayfish Metabolism, Katherine Paltz

Williams Honors College, Honors Research Projects

The effects of caffeine and additives commonly found in energy drinks were tested on crayfish to record changes, if any, in their metabolism. Three experimental groups were studied: 1. Caffeine; 2. Caffeine + Glucuronolactone; 3.) Caffeine + Glucuronolactone + Taurine. Caffeine is a common stimulant used to improve mental awareness, headaches, memory, and athletic performance. Glucuronolactone is connected with cardiovascular issues and aggressive behavior. Taurine is said to improve mood and focus. The experiment was performed at two different caffeine levels: 600mg and 1200mg for an initial 1 hour of exposure and 10 hours after exposure used as a pseudo-baseline. …