Neuroscience and Neurobiology Commons^™

Plasma S100Β Is A Predictor For Pathology And Cognitive Decline In Alzheimer’S Disease, Geetika Nehra, Bryan J. Maloney, Rebecca Smith, Wijitra Chumboatong, Erin L. Abner, Peter T. Nelson, Björn Bauer, Anika M. S. Hartz

UK CARES Faculty Publications

Background Blood–brain barrier dysfunction is one characteristic of Alzheimer’s disease (AD) and is recognized as both a cause and consequence of the pathological cascade leading to cognitive decline. The goal of this study was to assess markers for barrier dysfunction in postmortem tissue samples from research participants who were either cognitively normal individuals (CNI) or diagnosed with AD at the time of autopsy and determine to what extent these markers are associated with AD neuropathologic changes (ADNC) and cognitive impairment.

Methods We used postmortem brain tissue and plasma samples from 19 participants: 9 CNI and 10 AD dementia patients who …

Neural And Computational Approach To Understanding Environmental Modulation Of Behavioral Identity In Zebrafish, John W. Hageter

Graduate Theses, Dissertations, and Problem Reports (ETD)

Organisms rely on behavior for survival. Animals engage in behaviors that allow for feeding, mating, exploring and navigating their environment among others. Necessary for these behaviors to develop are the environmental factors and underlying circuitry which make behavior possible. Specifically, how the environment guides underlying neural circuitry to develop unique facets or phenotypes of a larger behavior are key to understanding why unique behaviors exist. In this thesis, I build foundational evidence for determining these mechanisms through the use of the zebrafish local search behavior. This is a behavior that zebrafish employ following the loss of environmental illumination where they …

Blood Biomarkers In Down Syndrome: Facilitating Alzheimer’S Disease Detection And Monitoring, Melissa E. Petersen, Lisi Flores-Aguilar, Elizabeth Head, Laia Montoliu-Gaya, Andre Strydom, Sarah E. Pape, Juan Fortea, Nicholas J. Ashton, Chinedu Udeh-Momoh, Sid E. O’Bryant, Dwight German, Florin Despa, Mark Mapstone, Henrik Zetterberg

Neurology Faculty Publications

Blood-based biomarkers continue to be explored for disease detection, monitoring of progression, and therapeutic outcomes as the diagnostic determination of Alzheimer’s Disease in Down Syndrome (DS-AD) remains challenging in clinical settings. This perspective highlights the current status of this effort. Overall, amyloid (A), tau (T), and neurodegeneration (AT[N]) blood-based biomarkers have been shown to increase with disease pathology for individuals with DS. Phosphorylated tau biomarkers (p-tau217, p-tau181) have been consistently shown to track disease progression for DS-AD and are likely good candidates for use in clinical settings. Biomarkers of inflammation (glial fibrillary acidic protein) also show promise; however, additional work …

Effect Of Paxlovid On Neurodevelopmental Disorder Diagnosis Outcomes In Offspring Of Mothers Infected With Sars-Cov-2 During Pregnancy, Simone Rogers

CMC Senior Theses

The onset of the 2020 COVID-19 pandemic brought concern over the effects that this virus would have on pregnancy and fetal outcomes, specifically neurodevelopmental outcomes. Maternal immune activation (MIA), caused by infection during pregnancy, is known to result in neurodevelopmental disorder (NDD) diagnosis in offspring, typically autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD). This effect has already been observed in mothers who were infected with COVID-19 during pregnancy. However, in 2023, Paxlovid, the COVID-19 antiviral drug, became available to patients experiencing symptoms of the virus, including pregnant women. Consequently, this study seeks to determine whether the risk of …

Weighted Family History Density Of Substance Use: Influence On Participant Substance Use Onset, Escalation, And Duration, Carleigh A. Litteral

Theses and Dissertations--Psychology

Substance use disorders impose a staggering toll on the United States (U.S.), straining healthcare systems, destabilizing communities, and profoundly impacting both individuals and families. Approximately one in six Americans aged 12 and older had a past-year substance use disorder in 2022 (Key Substance Use, 2022), and nearly one-third of adults experience a substance use disorder in their lifetime (Wu, 2010), contributing to an economic burden exceeding $400 billion annually (National Drug Threat Assessment, 2011). Family history of substance use disorders is a key predictor of vulnerability, with individuals who have affected relatives being 2–8 times more …

Effect Of Family-Centered Care Interventions On Motor And Neurobehavior Development Of Very Preterm Infants: A Systematic Review And Meta-Analysis, Manasa Kolibylu Raghupathy, Shradha S. Parsekar, Shubha R. Nayak, Kalesh M. Karun, Sonia Khurana, Alicia J. Spittle, Leslie Edward S. Lewis, Bhamini Krishna Rao

Rehabilitation Sciences Faculty Publications

Aim

To assess the effectiveness of family-centered care (FCC) interventions on motor and neurobehavior development of very preterm infants.

Method

Randomized and quasi-randomized trials assessing the effect of FCC on motor and neurobehavioral outcomes in very preterm infants (28–32 wk gestation) were included. Five electronic databases and grey literature were searched from January 2010 to August 2022. Two reviewers independently screened the titles/abstracts and full texts, assessed the risk of bias, and extracted data. The Cochrane Risk of Bias 2.0 Tool and GRADE were used for risk and evidence certainty assessments. Meta-analysis or narrative synthesis was performed based on data …

Investigating Tumor Growth And Regulation In Supratentorial Ependymomas; The Impact Of Dlk1 And Egr1 Knockout, Om Sinojia

Honors Scholar Theses

Ependymomas (EPNs) are primary brain tumors that often arise from radial glial cells lining the ventricular system. Supratentorial ependymomas (ST-EPNs) are particularly aggressive, and understanding the molecular factors driving their growth is critical for developing targeted therapies. This study investigates the roles of DLK1 and EGR1, key regulators in cellular differentiation and tumorigenesis, in the development of ST-EPNs. We utilized genetically engineered mouse models to induce postnatal knockouts of DLK1 and EGR1 and evaluated tumor growth using histological and imaging techniques. Tumor area was quantified across multiple brain sections from both male and female mice. DLK1 knockout brains exhibited consistent …

Increased Neuroinflammation And Compromised Blood Brain Barrier In A Mouse Model Of Autism, Amani S. Ikram, Rekha Jagadapillai, Idil Tuncali, Gregory N. Barnes, Evelyne Gozal

The Cardinal Edge

No abstract provided.

Parallel Electrophysiological Abnormalities Due To Covid-19 Infection And To Alzheimer’S Disease And Related Dementia, Yang Jiang, Jennifer Neal, Pradoldej Sompol, Görsev Yener, Xianghong Arakaki, Christopher M. Norris, Francesca R. Farina, Agustin Ibanez, Susanna Lopez, Abdulhakim Al-Ezzi, Voyko Kavcic, Bahar Güntekin, Claudio Babiloni, Mihály Hajós

Neurology Faculty Publications

Many coronavirus disease 2019 (COVID-19) positive individuals exhibit abnormal electroencephalographic (EEG) activity reflecting “brain fog” and mild cognitive impairments even months after the acute phase of infection. Resting-state EEG abnormalities include EEG slowing (reduced alpha rhythm; increased slow waves) and epileptiform activity. An expert panel conducted a systematic review to present compelling evidence that cognitive deficits due to COVID-19 and to Alzheimer’s disease and related dementia (ADRD) are driven by overlapping pathologies and neurophysiological abnormalities. EEG abnormalities seen in COVID-19 patients resemble those observed in early stages of neurodegenerative diseases, particularly ADRD. It is proposed that similar EEG abnormalities in …

Characterizing Border Associated Macrophages During Spinal Cord Regeneration, Addison Vogt, Dana Shaw, Mayssa Mokalled

Undergraduate Research Symposium

The human central nervous system has limited regenerative ability, with injuries to the spinal cord (SC) often resulting in paralysis. Alternatively, zebrafish have enhanced innate regenerative capacity and regain full motor function following spinal cord injury (SCI). Immune activation following SCI is necessary to provide a permissive environment for tissue repair, but the immune pathways necessary for SC regeneration are not well characterized. In previous data, we have found that while immune activation is persistent into the chronic phases of SCI response in mammals, zebrafish achieve full immune clearance within 48 days post SCI. We hypothesize that one key distinction …

Multiple Guidance Mechanisms Control Axon Growth To Generate Precise T-Shaped Bifurcation During Dorsal Funiculus Development In The Spinal Cord, Bridget M. Curran, Kelsey R. Nickerson, Andrea R. Yung, Lisa V. Goodrich, Alexander Jaworski, Marc Tessier-Lavigne, Le Ma

Farber Institute for Neuroscience Faculty Papers

The dorsal funiculus in the spinal cord relays somatosensory information to the brain. It is made of T-shaped bifurcation of dorsal root ganglion (DRG) sensory axons. Our previous study has shown that Slit signaling is required for proper guidance during bifurcation, but loss of Slit does not affect all DRG axons. Here, we examined the role of the extracellular molecule Netrin-1 (Ntn1). Using wholemount staining with tissue clearing, we showed that mice lacking Ntn1 had axons escaping from the dorsal funiculus at the time of bifurcation. Genetic labeling confirmed that these misprojecting axons come from DRG neurons. Single axon analysis …

Cerebrovascular Reactivity Mri As A Biomarker For Cerebral Small Vessel Disease–Related Cognitive Decline: Multi-Site Validation In The Markvcid Consortium, Peiying Liu, Zixuan Lin, Kaisha Hazel, George Pottanat, Cuimei Xu, Dengrong Jiang, Jay J. Pillai, Emma Lucke, Christopher E. Bauer, Brian T. Gold, Steven M. Greenburg, Karl G. Helmer, Kay Jann, Gregory Jicha, Joel Kramer, Pauline Maillard, Rachel M. Mulavelil, Pavel Rodriguez, Claudia L. Satizabal, Kristin Schwab, Sudha Seshadri, Herpreet Singh, Ángel G. Velarde Dediós, Danny J. J. Wang, Rita R. Kalyani, Abhay Moghekar, Paul B. Rosenberg, Sevil Yasar, Marilyn Albert, Hanzhang Lu

Neurology Faculty Publications

INTRODUCTION: Vascular contributions to cognitive impairment and dementia (VCID) represent a major factor in cognitive decline in older adults. The present study examined the relationship between cerebrovascular reactivity (CVR) measured by magnetic resonance imaging (MRI) and cognitive function in a multi-site study, using a predefined hypothesis.

METHODS: We conducted the study in a total of three analysis sites and 263 subjects. Each site performed an identical CVR MRI procedure using 5% carbon dioxide inhalation. A global cognitive measure of Montreal Cognitive Assessment (MoCA) and an executive function measure of item response theory (IRT) score were used as outcomes.

RESULTS: CVR …

Wired For Success: A Neurobiological Approach To Improving The Academic Outcomes Of Middle School Boys, Allison Emery

University Honors Theses

Male accomplishment in scholastic settings has been declining globally for the last decade, leading to long-term consequences for boys and men. Possible neurobiological underpinnings of the gender gap in education are discussed in this literature review. While male and female differences have, in the past, largely been considered socialized, recent science also confirms neurobiological variances between male and female development. These distinctions are assessed for their potential ties to the decline in male academic success, and are correlated to classroom practices, strategies and interventions meant to increase boys' engagement and performance.

Genomic Data Science Approaches For Understanding Human Diseases, Snehal Shah

All Dissertations

The intricate interplay of genetic predisposition, environmental influences, and lifestyle acts as the multifactorial landscape of diseases. Understanding this complexity presents a significant challenge. Molecular insights into disease mechanisms, particularly the interactions of DNA, RNA, and proteins with environmental and lifestyle factors, have revolutionized disease diagnosis, prognosis, and treatment. High-throughput technologies, such as next-generation sequencing, generate large amounts of molecular data, holding a wealth of knowledge. These datasets unveil the roles of genes and their interactions with various factors through analysis, shedding light on previously unknown molecular mechanisms underlying disease pathogenesis. Furthermore, they facilitate the discovery of biomarkers crucial for …

Decentralized Clinical Trials For Medications To Reduce The Risk Of Dementia: Consensus Report And Guidance, Leanne Howard, Carla Abdelnour, Erin Abner, Ricardo F. Allegri, Hiroko H. Dodge, Serge Gauthier, Camilla M. Hoyos, Gregory Jicha, Patrick G. Kehoe, Catherine J. Mummery, Adesola Ogunniyi, Nikolaos Scarmeas, Xiaoying Chen, Jodie R. Titiner, Christopher R. Weber, Ruth Peters

Neurology Faculty Publications

INTRODUCTION: Recent growth in the functionality and use of technology has prompted an increased interest in the potential for remote or decentralized clinical trials in dementia. There are many potential benefits associated with decentralized medication trials, but we currently lack specific recommendations for their delivery in the dementia field.

METHODS: A modified Delphi method engaged an expert panel to develop recommendations for the conduct of decentralized medication trials in dementia prevention. A working group of researchers and clinicians with expertise in dementia trials further refined the recommendations.

RESULTS: Overall, the recommendations support the delivery of decentralized trials in dementia prevention …

Effects Of A Cb1 Receptor Antagonist On Anxiety In Adult Rats Exposed To Thc During Development, Jennifer Aguilera-Fonseca, Karla Colley, Atoria Hamm, Eddie Galarza, Joe Morse, Rachel Ntor, Destiny Pichardo, Vincent P. Markowski

McNair Scholars Program

No abstract provided.

Towards A New Role Of Mitochondrial Hydrogen Peroxide In Synaptic Function, Cliyahnelle Z. Alexander

Student Theses and Dissertations

Aerobic metabolism is known to generate damaging ROS, particularly hydrogen peroxide. Reactive oxygen species (ROS) are highly reactive molecules containing oxygen that have the potential to cause damage to cells and tissues in the body. ROS are highly reactive atoms or molecules that rapidly interact with other molecules within a cell. Intracellular accumulation can result in oxidative damage, dysfunction, and cell death. Due to the limitations of H₂O₂ (hydrogen peroxide) detectors, other impacts of ROS exposure may have been missed. HyPer7, a genetically encoded sensor, measures hydrogen peroxide emissions precisely and sensitively, even at sublethal levels, during …

Early Developmental Exposure To Δ9-Tetrahydrocannabinol Causes Latent Behavioral, Growth, And Bioenergetic Effects In Danio Rerio, Astra Hahm

Honors Theses

Early developmental exposure to Δ9-tetrahydrocannabinol causes latent behavioral, growth, and bioenergetic effects in Danio rerio

(Under the direction of Dr. Kristine Willett)

Δ9-tetrahydrocannabinol (Δ9-THC) is used during pregnancy to mitigate symptoms such as nausea, pain, and insomnia. It is established that Δ9-THC exposure early in life causes adverse effects in children’s development including behavioral disorders. Our goal was to determine the latent and generational impacts on growth, behavior, and mitochondrial bioenergetics following exposure to Δ9-THC. Wildtype (5D) zebrafish were exposed to 0 (0.05% DMSO), 0.08, 0.4, or 1 µM Δ9-THC from 6-96 hours post-fertilization (hpf), then subsequently raised in clean …

Immunopathogenesis Of Post-Infectious Hydrocephalus, Sascha Powers Bernier

Honors Scholar Theses

Hydrocephalus is characterized by the abnormal accumulation of cerebrospinal fluid (CSF) within the brain ventricles. In post-infectious hydrocephalus (PIH) cases, the condition presents challenges in understanding the immune response. PIH is a complex condition, often persisting after the initial infection is treated and thus requiring a deeper understanding of the immune mechanisms involved in its development. This thesis will explore the immunopathogenesis of PIH, elucidating the relationship between the immune response and neurological complications that would succeed infection. The immune response of PIH includes a series of events, beginning with the activation of immune cells and finishing with the release …

Compensatory Changes In The Visual System As A Result Of Neurodegeneration, Liz Bierlein

Theses & Dissertations

The brain has the remarkable ability to compensate for damage and maintain physiological set points. In the visual system where even after significant damage has been done, the brain fills in visual gaps because of this compensation. This thesis attempts to understand several components of visual changes after damage in disorders such as glaucoma. This was accomplished by using several models of vision loss in mice including the DBA/2J (D2) and silicone oil (SO) models of glaucoma, the RD10 model of retinitis pigmentosa, and a retina-specific knockout of brain-derived neurotrophic factor (BDNF)— the Chx10-cre; BDNF^fl/fl mouse. Through these models …

Individual Differences In Age And Testosterone Are Uniquely Associated With Neural Oscillatory Activity Serving Verbal Working Memory In Children And Adolescents, Abraham D. Killanin

Theses & Dissertations

During the sensitive period of adolescence, the human brain undergoes dynamic changes in structure and function resulting in vast executive function gains. Verbal working memory (VWM) is one executive function that serves as a foundation to language acquisition, reading, and learning. Many have examined the development of VWM in youth, but few have probed age-related changes in the underlying neural oscillatory dynamics, and none have examined testosterone-related changes. We recorded magnetoencephalography during a modified Sternberg VWM task in 82 youth participants aged 6 – 14 years old and collected salivary testosterone samples. Significant oscillatory responses were identified and imaged using …

Pediatric Neurotropic Infection Alters Synaptic Development In The Developing Brain, Anuoluwapo Grace Fadare, Yashika S. Kamte, Manish N. Chandwani, Lauren A. O'Donnell

Rowan-Virtua Research Day

Many neurotropic viruses cause more significant pathology in younger hosts as their brains are still developing. This experiment asked how central nervous system (CNS) viral-infections affect the development of synapses in the pediatric brain during infection and post-infection. Synaptogenesis is at its peak in pediatric mice (10 days old) and we hypothesized that a neurotropic infection could disrupt synaptic proteins. We used a transgenic mouse model where measles virus (MV) infects only mature neurons, leading us to question whether synapses were impacted. We examined synaptic markers in the cerebellum and hippocampus in MV-infected and uninfected mice 9 days and 90 …

Towards Understanding The Function Of An Ets-Like Gene In Nematostella Vectensis: Generation Of A Knockout Mutant Line And A Transgenic Reporter Line, Emily Bullock

Biological Sciences Undergraduate Honors Theses

Due to their unique phylogenic position as sister to Bilateria, Cnidaria are often credited with the utility of allowing for reconstruction of ancestral biology based on characteristics shared with bilaterians and other animals. This factor makes investigation into the nervous systems of cnidarians critical in understanding early neural evolution. Wamides, a class of neuropeptides, have been shown to play a regulatory role in life cycle transitions across many different species. The cnidarian specific Wamide neuropeptide, GLWamide, has previously been identified to play an accelerator role in the metamorphic timing of a specific species of sea anemone, Nematostella vectensis. However, …

Loss Of Tsc2 Results In Abnormal Postnatal Neurogenesis And Striatal Hamartomas, Victoria Riley

All Dissertations

Billions of years of evolution have culminated in the most complex organ in all of biology: the brain. Its capacity to sense, store, and predict information uniquely bestows humans with the capability to generate art, music, language, and math and sets humans apart from other species. It is therefore prudent and worthwhile to study the brain and its development. A critical aspect of brain development is neurogenesis, or the production of neurons. Neurogenesis is facilitated by neural stem cells (NSCs) and is influenced by the mTORC1 signaling pathway. For NSCs to differentiate and become committed to a neuronal cell fate, …

Use Of Cre-Lox Mice As A Model For Ependymogenesis, Poorva Bagchee

Honors Scholar Theses

Stem cells in the lateral ventricles of the brain undergo a process of development within the ventricular-subventricular zone. In early development neuroepithelial cells divide to form more neuroepithelial cells or convert to radial glial cells (RGCs). These RGCs, or stem cells, then divide to form neurons or other glial cells such as ependymal cells, which form a single-layered ependyma along the ventricular wall. These stem cells divide in two ways: symmetrically, producing two ependymal cells or asymmetrically, yielding one neural stem cell and ependymal cell. To further study this process the Cre-lox system in mice will be used. By breeding …

Perinatal Buprenorphine Effects On Offspring Growth, Opioid Withdrawal, And Brain Morphology In Rats, Parker Barnes

Electronic Theses and Dissertations

Opioid use disorder (OUD) impacts 5.6 million people in the US. Buprenorphine (BUP) is a commonly prescribed opioid medication used to treat OUD, including in pregnant women. However, opioid use during pregnancy is associated with poorer infant outcomes including reduced fetal growth, neurodevelopmental deficits, and neonatal opioid withdrawal syndrome (NOWS). Recent clinical data suggests that providing mothers with a lower dose of BUP may result in fewer negative outcomes in infants. Here, a preclinical rodent model of low-dose perinatal BUP exposure was used to study offspring health outcomes in the neonate, juvenile, and adolescent offspring. Dams were given clinically relevant …

Biophysical Model Of Retraction Motor Neurons And Their Modification By Operant Conditioning, Maria Rasheed

Dissertations and Theses (Open Access)

Operant conditioning (OC) is a form of associative learning in which an animal modifies its behavior based on the consequences that follow that behavior. Despite its ubiquity, the underlying mechanisms of OC are poorly understood. Insights into the mechanisms of OC can be obtained by studying Aplysia feeding behavior as it can be modified by OC. This behavior is mediated by a central pattern generator (CPG) network in the buccal ganglia that contains a relatively small number of neurons. This CPG generates rhythmic motor patterns (BMPs) that move food into the gut by closing a tongue-like structure (i.e., radula) during …

Development Of Vasculature Patterns In A Mouse Model Of Supratentorial Ependymoma, Jackson Ayers

Honors Scholar Theses

Supratentorial Ependymoma (ST-EPN) is a subtype of ependymoma, a primary solid tumor found throughout the nervous system. ST-EPN are most commonly caused by an oncogenic fusion between the zinc finger gene ZFTA and the RELA, and this distinct ependymoma subtype is readily modeled in mice by conditional expression of ZFTA-RELA in radial glial cells. ST-EPN are known to have a distinctive arrangement of tumor cells and vasculature forming pseudo-rosettes in which polarized tumor cells surround blood vessels within the tumors. It is not known how these pseudo-rosettes or the tumor vasculature form and develop in ST-EPN, so in this study …

Exploring The Developmental Effects Of Antidepressants In Caenorhabditis Elegans, Alexandra Van Stone

Annual Research Symposium

It is so important to explore the potential side effects of antidepressants especially if these side effects could lead to a future detriment to an individual’s financial and social well-being. A better understanding of these side effects in regards to human developmental issues is imperative considering issues related to mental health and depression affect a large percentage of the population. In this study, we tested if Caenorhabditis (C.) elegans could be a potential model organism to predict possible side effects associated with select antidepressants. Their developmental problems potentially encountered upon drug treatment may be encountered in humans.

Alzheimer’S Disease And Inflammatory Biomarkers Positively Correlate In Plasma In The Uk-Adrc Cohort, Kate E. Foley, Zachary Winder, Tiffany L. Sudduth, Barbara J. Martin, Peter T. Nelson, Gregory Jicha, Jordan P. Harp, Erica M. Weekman, Donna M. Wilcock

Neurology Faculty Publications

INTRODUCTION: Protein-based plasma assays provide hope for improving accessibility and specificity of molecular diagnostics to diagnose dementia. METHODS: Plasma was obtained from participants (N = 837) in our community-based University of Kentucky Alzheimer’s Disease Research Center cohort. We evaluated six Alzheimer’s disease (AD)- and neurodegeneration-related (Aβ40, Aβ42, Aβ42/40, p- tau181, total tau, and NfLight) and five inflammatory biomarkers (TNF𝛼, IL6, IL8, IL10, and GFAP) using the SIMOA-based protein assay platform. Statistics were performed to assess correlations. RESULTS: Our large cohort reflects previous plasma biomarker findings. Relationships between biomarkers to understand AD–inflammatory biomarker correlations showed significant associations between AD and inflammatory …