Neuroscience and Neurobiology Commons^™

Brain Gains: A Review Of Remediation Treatment Strategies Using Exercise Following Traumatic Brain Injury, Jessica Smith, Kristin Biggins, Loriann Helgeson

The Open Journal of Occupational Therapy

In this Opinions in the Profession article, we explore remediation treatment strategies using exercise for recovery from post-traumatic brain injury and aim to justify the use of such treatment in the occupational therapy profession to increase skills for functional gain. Common treatment strategies used by occupational therapists after brain injury are compensatory strategies, indicating the client learns a new way to perform the task. Though effective, it is also necessary to consider how remediation and neuroplasticity are essential. Teaching new approaches to complete tasks results in functional gains; however, focusing on foundational skills using exercises to relearn motor patterns to …

The Role Of Extracellular Vesicles As Diagnostic Tools In Gut-Brain Axis Disorders, Patricia Marçal Da Costa, Paulo Iury Gomes Nunes, Gabriella Cunha Vieira Ciurleo, José Wagner Leonel Tavares Junior, Pedro Braga Neto, Ludmila Belayev, Reinaldo Barreto Oriá

School of Graduate Studies Faculty Publications

The gut–brain axis represents a dynamic two-way signaling network whose dysregulation has been implicated in a wide range of neurogastrointestinal disorders. In this context, extracellular vesicles (EVs) have emerged as critical mediators of intercellular signaling and as promising non-invasive biomarkers. Derived from host and microbial cells, EVs carry bioactive cargo—including proteins, lipids, nucleic acids, and metabolites—that reflect the physiological or pathological state of their cells of origin. Their ability to cross biological barriers, such as the blood–brain barrier, underscores their potential for diagnosing and monitoring gut–brain axis dysfunctions. In this mini-review, we integrate microbial and brain-derived EVs within the framework …

Accelerating The Discovery Of The Genetic And Molecular Bases Of Neurodevelopmental Disorders In Vivo Using Breasi-Crispr, Claire Mae Kittock

Dissertations and Theses

Many neurodevelopmental disorders occur due to perturbations in prenatal brain development. More genetic variants associated with neurodevelopmental disorders are continuously being identified. However, there is a lack of understanding of the pathogenic mechanisms. Here, we describe a novel application of the technique Breasi-CRISPR in modeling specific patient variants in the embryonic mouse brain. Breasi-CRISPR is a highly efficient system combining in utero electroporation with CRISPR-CAS9 genome editing. We hypothesized that Breasi-CRISPR would be sufficient at inserting patient analogous variants into endogenous loci to be used as a new paradigm for modeling neurodevelopmental disorders. We aimed to test if Breasi-CRISPR could …

The Neuroprotective And Synergistic Effects Of Carbamoylated Erythropoietin And Insulin-Like Growth Factor-1 In Alzheimer's Disease, Morgan Jean Rothschadl

Dissertations and Theses

Alzheimer’s disease (AD) is a prominent neurodegenerative disease characterized by a decline in cognitive functioning. While current FDA-approved therapeutics exist, they fall short in creating significant and long-lasting improvements to cognition. A newer approach using neurotrophic factors has shown promising effects on improving cognition in clinical trials. Neurotrophic factors are secreted proteins that have multimodal effects in the brain, including supporting cell survival and functioning. Two neurotrophic factors of interest are carbamoylated erythropoietin (CEPO) and insulin-like growth factor-1 (IGF-1), and the goal of this study was to understand the synergistic and neuroprotective effects of CEPO and IGF-1 in AD. We …

Glial Cytokine Modulation Improves Sleep And Circadian Disruption In Female Saa Knock-In Mice Of Alzheimer’S-Related Pathology, Teresa Macheda, Margaret R. Hawkins, Carrie E. Johnson, Madison G. Lapid, Haleigh R. Whitlock, Savannah M. Shepard, Makayla F. Cox, Kelly N. Roberts, Leke Bytyqi, Heather M. Hash, Omar A. Abou El-Ezz, Mohammed Abou El-Ezz, Katharina Kohler, Sridhar Sunderam, Bruce F. O'Hara, Linda J. Van Eldik, Michael Paul Murphy, Marilyn J. Duncan, Adam D. Bachstetter

Neuroscience Faculty Publications

Introduction: Sleep and circadian disturbances are early Alzheimer's disease (AD) features, yet mechanisms linking amyloid pathology, neuroinflammation, and sex differences remain unclear.

Methods: We longitudinally assessed sleep, circadian rhythms, and cognition in female and male hAPP^SAA knock-in and control mice from 2 to 19 months using piezoelectric monitoring. Aged mice (15 months) received MW151, a glial cytokine inhibitor (2.5 mg/kg, every other day, 6 weeks).

Results: Only females exhibited midlife reductions in light-phase sleep, increased rhythm fragmentation, and reduced rhythm stability, coinciding with selective reversal learning deficits, effects independent of amyloid or cytokine burden. MW151 increased light-phase sleep and …

From Fog To Function: An Occupational Therapist's Guide To Evaluating And Treating Cancer-Related Cognitive Impairments, Lauren E. Toner

Entry-Level Occupational Therapy Doctorate - Doctoral Capstone Symposium

Cancer – related cognitive impairment (CRCI) is a common side effect of cancer treatment that interferes with cancer survivors’ occupational performance, independence, and quality of life. Despite its high prevalence, CRCI remains under recognized and inconsistently addressed within oncology care. About 70% of individuals diagnosed with cancer report cognitive changes during or after treatment, yet many do not receive treatment. Occupational therapists are clinically trained to evaluate and treat functional cognition, activities of daily activities, instrumental activities of daily living, and client centered goals, positioning them as key providers in addressing CRCI. However, limited occupational therapy specific resources have hindered …

Planaria Dugesia Japonica As A Model Organism For Measuring The Toxicity Of Environmental Contaminants Per- And Poly-Fluoroalkyl Substances (Pfas), Caitlyn Rodeo

Behavioral Neuroscience Honors Papers

A group of synthetic chemicals, per- and poly-fluoroalkyl substances (PFAS) are ubiquitous in the environment and have significant detrimental effects on physiology and behavior. Planaria have recently increased in popularity as a model for toxicology and regeneration research. These organisms possess a primitive centralized nervous system that is thought to be more similar to the vertebrate brain than to other invertebrate brains in terms of structure and function, and possesses the same neuronal subpopulations and neurotransmitters as the mammalian brain. While other studies have investigated the behavioral effects of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) on planaria, there is …

Music, Eeg And Stress: Connections Between Music And Electroencephalographic Patterns And The Mediation Of Physiological And Psychological Stress, Alexa Warren

Behavioral Neuroscience Honors Papers

The interrelation between music and the brain is an evolving interdisciplinary interest within neuroscience research. Relying on the capacity of music to elicit emotional and physical responses, as well as scientific principles like entrainment, this area of research explores the potential for utilizing targeted music as a holistic non-pharmacological therapeutic intervention. This is often executed via musical entrainment, which is the basis for this study. Utilizing a complex, yet elegant design, this research incorporates a cross disciplinary approach into a randomized controlled study bridging science and the arts. The purpose of this study is to expand this body of knowledge …

Expectancy Effects On Mental Fatigue, Ethan Li

Behavioral Neuroscience Honors Papers

This thesis explores mental fatigue as a state arising from sustained cognitive demand and explores the use of the gradual-onset performance task (gradCPT) for mental fatigue research. The study examines whether expectancy effects (placebo or nocebo conditions) influence mental fatigue-related outcomes. Expectancy effects were induced by asking participants to view an inert optical illusion after describing its benefits (placebo) or harms (nocebo) to mental fatigue. Out of 73 participants, results showed significant decreases in performance over time, along with significantly increased subjective fatigue as measured by the VAS-F subscale, supporting gradCPT as an effective fatigue inducer in short periods of …

Perinatal Inflammation And Oxidative Stress Alter Adult Rat (Rattus Norvegicus) Motor Behavior, Alexander Young

Honors College Theses

Recent evidence in comparative animal models suggests that early life exposure to elevated inflammation (via LPS exposure) and oxidative stress (via acetaminophen exposure) may synergistically interact to alter typical neurodevelopmental trajectories, resulting in lasting effects on both behavior and gut-brain neurochemistry. The current study observed emotional and motor behaviors and collected fecal-boli to measure Tyrosine (TE) levels in male and female Long-Evans (Rattus norvegicus) rats. Subjects were either treated with [1] saline [2] lipopolysaccharide (LPS) to introduce an inflammatory state, [3] acetaminophen (APAP) to introduce oxidative stress, or [4] a dual-hit of both LPS + APAP on postnatal day (PD) …

17Β Estradiol Protection Against Medium-Change Neurotoxicity In Organotypic Hippocampal Slice Cultures, Autumn B. Stage

University of Kentucky Master's Theses

Medium change neurotoxicity can disrupt glutamate homeostasis and promote excitotoxic neuronal injury through excessive NMDA receptor activation. 17β estradiol (E2) has demonstrated neuroprotective effects in models of neuronal injury and may regulate glutamatergic signaling through metabotropic glutamate receptors (mGluR2/3). This study investigated whether E2 protects against medium change associated neurotoxicity in organotypic hippocampal slice cultures whether responses differed by sex or hippocampal region. Hippocampal slices from postnatal day 8 male and female Sprague Dawley rats were maintained in culture and exposed to 1, 10, or 100 nM E2 for 24 hours following a five day recovery period. Propidium iodide (PI) …

The Complexities Of The Bilingual Advantage, Melisa Sierra

Behavioral Neuroscience Honors Papers

The bilingual advantage hypothesis, which proposes an enhancement of executive functions in bilinguals, remains heavily debated with inconsistent findings across studies. This study investigated working memory performance in bilingual and monolingual young adults using a modified n-back task with an interruption while recording EEG activity. Participants completed 1-back, 2-back, and 3-back conditions across the pre-interruption phase and a post-break 2-back condition. Behavioral measures (accuracy and response times) were analyzed alongside ERP, focusing on P300 and sustained activity components, were analyzed. Results showed a decrease in accuracy as task difficulty increased from 1-back to 3-back, indicating the expected effects of higher …

Rna-Sequence-Driven Identification Of Differentially Expressed Genes In Α-Crystallin-Deficient Zebrafish, Kehlie Hopper

SPARK Symposium Presentations

Fetal Alcohol Syndrome (FAS) is a condition that develops in infants when exposed to alcohol in utero, leading to physical impairments such as reduced eye size and disrupted retinal function. Alpha-crystallin A is a key structural protein required for proper lens development and maintenance of transparency, while Alpha-crystallin B plays a protective role against cellular stress during eye development. In this study, I compared AB wild-type (ABWT), αA-crystallin knockout (cryaa), and αB-crystallin knockout (cryaba) zebrafish to investigate how the loss of these proteins influences eye development under ethanol exposure. The cryaa mutants exhibited reduced eye size even under control conditions, …

Adapting To Uncertainty: Effects Of Environmental Instability On Zebrafish Behaviour, Britney Sekulovski

Theses and Dissertations (Comprehensive)

This thesis addresses how animals cope with unpredictability by testing how environmental stability changes the behaviour of zebrafish (Danio rerio) in two complementary experiments. In Experiment 1, fish lived for three months in either a Dynamic environment (water temperature, feeding times, habitat complexity, group size, and membership fluctuated) or a Stable environment (all factors constant). Across seven behavioural assays, measuring individual behavioural differences, collective movement, social memory, and information use, Dynamic condition fish were found to be more sensitive to social cues and more likely to conform to recent social information, independent of the quality of the information …

The Effects Of Environmental Complexity On Brain Development And Personality Expression In Western Hognose Snakes, Gokulan Nagabaskaran

Theses and Dissertations (Comprehensive)

There is growing interest in snake cognition, personality, and welfare as more snakes are kept as pets, yet little research has been conducted. The effects of enrichment and environmental factors have been well documented in other taxa, and recent evidence suggests that snakes may benefit in similar ways. This dissertation investigated the impact of environmental and social enrichment on personality expression, personality stability, and brain development. Western hognose snakes (Heterodon nasicus) were used as the model species, as they are a popular choice in the pet trade. This allows the research to be readily translatable to husbandry practices of many …

Temporal Evolution Of Brain Inflammation In The Bilateral Common Carotid Artery Stenosis Model Of Chronic Cerebral Hypoperfusion, Makayla F. Cox, Jill M. Roberts, Ryan K. Shahidehpour, David L. Dornbos Iii, Adam D. Bachstetter

Neuroscience Faculty Publications

Chronic cerebral hypoperfusion is a major contributor to vascular cognitive impairment and dementia, primarily through its disruption of white matter integrity and promotion of neuroinflammatory cascades. The bilateral common carotid artery stenosis (BCAS) model has emerged as the predominant experimental approach for studying the effects of chronic cerebral hypoperfusion, particularly in aging-relevant contexts. This review synthesizes current knowledge of inflammatory responses in the BCAS model, with an emphasis on their temporal progression and functional consequences. We begin by outlining the clinical burden of hypoperfusion, the rationale for BCAS, and the hemodynamic phases it produces. We then examine early neurovascular unit …

Dim Light At Night Impacts Circadian Rhythms And Alzheimer’S Disease-Like Neuroinf Lammation And Neuropathology In Humanized App Saa Knock-In Mice, Marilyn J. Duncan, Margaret R. Hawkins, Leke Bytyqi, Haleigh R. Whitlock, Savannah M. Shepard, Makayla F. Cox, Esther G. Drinkard, Teresa Macheda, Kelly N. Roberts, Katharina Kohler, Mary-Claire Schmidt, Carrie E. Johnson, Sridhar Sunderam, Bruce F. O'Hara, Michael Paul Murphy, Adam D. Bachstetter

Neuroscience Faculty Publications

Artificial light at night (light pollution) is widespread but understudied in the context of Alzheimer’s disease (AD). Sleep and circadian disruption have been linked to amyloid-β (Aβ) accumulation and neuroinflammation, but whether dim light at night (dLAN) modifies these processes remains unclear. We tested whether chronic dLAN exposure (8 lux during the dark phase, 8 weeks) alters circadian rhythms, amyloid pathology, and neuroinflammation in 12–13 month-old humanized APP knock-in (KI) mice. hAPP^SAA KI mice, which develop plaques, were compared with hAPP^WT KI controls carrying only a humanized APP sequence. dLAN reduced circadian rhythm amplitude and stability while increasing …

A Framework For Characterizing The Peripheral Immune Isonome Using Long-Read Single-Cell Rna Sequencing And Its Relevance To Neurological Disease, Patricia Hayes Doyle

Theses and Dissertations--Neuroscience

Long-read single-cell RNA sequencing provides an opportunity to understand human health and disease at isoform resolution, revealing cellular diversity and disease mechanisms difficult to resolve with bulk or short-read methodologies.

Using a modified PIPseq workflow and computational pipeline adapted for Oxford Nanopore (ONT) sequencing, we profiled isoform usage across immune cells, integrating marker expression and isoform discovery, generating the largest long-read single-cell dataset of human immune cells from a single individual to date. We identified non-canonical protein-coding variants of GZMB and CD3G enriched in unexpected cell types. We also discovered novel transcripts from CMC1 and LYAR with cell-type-specific signatures that …

Metabolism As A Regulator Of Sleep And Cortical Activity In Health And Alzheimer’S Disease, Nicholas J. Constantino

Theses and Dissertations--Neuroscience

Metabolic flexibility is essential for maintaining normal physiological function, enabling an organism to sense, flux, utilize, and switch fuel sources in response to changing energetic availability, demand, and cellular needs. Energetic demands are state-dependent, with wake and sleep exhibiting distinct metabolic profiles. Sleep is highly sensitive to changes in metabolism and requires metabolic flexibility to both transition into and maintain sleep stability. Alzheimer’s disease (AD) is increasingly recognized as a disease of altered metabolism yet is often framed as a disease of energetic failure. We instead define AD as a disease of metabolic inflexibility, characterized not by insufficient energy availability, …

Design And Advancement Of Analytical Frameworks For In Vivo Single-Photon Calcium Imaging To Characterize Temporal- And Treatment-Dependent Neural Adaptations To Opioid Exposure And Withdrawal In The Medial Prefrontal Cortex, Alexia R. Alsum Dr.

Theses and Dissertations--Pharmacy

Despite the availability of several approved medications for opioid use disorder (OUD), it remains a significant public health concern characterized by persistent neurobiological adaptations that drive relapse and impede successful recovery. The medial prefrontal cortex (mPFC), a region critical for executive control and decision-making, undergoes pronounced functional changes during chronic opioid exposure and withdrawal, yet the cellular mechanisms underlying these adaptations remain poorly understood. This dissertation aims to investigate longitudinal alterations in mPFC neural activity across opioid exposure and withdrawal using in vivo single-photon calcium imaging and newly developed computational frameworks.

Following standard preprocessing to extract and normalize calcium traces, …