Developmental Neuroscience Commons^™

Metoprolol Disrupts Sterol Biosynthesis Through Inhibition Of 7-Dehydrocholesterol Reductase (Dhcr7), Luke B. Allen

Theses & Dissertations

Cholesterol is essential for life. It is particularly important in the brain as it relies on de novo synthesis of cholesterol following the formation of the blood brain barrier (BBB). As such, disrupting sterol biosynthesis during neurodevelopment can have devastating outcomes. The most common post-lanosterol sterol biosynthesis disorder, Smith-Lemli-Opitz Syndrome, arises from a faulty DHCR7 enzyme. DHCR7 has also been shown to be inhibited by several psychotropic medications. Here we assess six beta-blockers and their effects on sterol biosynthesis in vitro. Two beta-blockers, metoprolol and nebivolol strongly inhibit DHCR7 in four separate in vitro models of both mouse and …

Med12 Is A Critical Regulator Of Neural Crest Lineage And Nervous System Myelination, Fatma Betul Aksoy Yasar

Dissertations & Theses (Open Access)

The Mediator complex (MED) is a multi-subunit protein complex integral to the eukaryotic transcription machinery. MED12 is a Cdk8- regulatory kinase module subunit directly implicated in human disease and is genetically altered in neurological disease and cancer. Numerous attempts at generating an in vivo system to study the role of Med12 failed due to embryonic lethality associated with germline or developmental disruption of Med12 gene. To understand the cellular and molecular processes associated with its role in disease, we generated multiple mouse models with targeted depletion of MED12 in distinct cellular lineages. Our genetically engineered models with induced and conditional …

Distinct Thalamic And Frontal Neuroanatomical Substrates In Children With Familial Vs. Non-Familial Attention-Deficit/Hyperactivity Disorder (Adhd), Rahman Baboli, Meng Cao, Jeffrey M. Halperin, Xiaobo Li

Publications and Research

Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent, inheritable, and heterogeneous neurodevelopmental disorder. Children with a family history of ADHD are at elevated risk of having ADHD and persisting its symptoms into adulthood. The objective of this study was to investigate the influence of having or not having positive family risk factor in the neuroanatomy of the brain in children with ADHD. Cortical thickness-, surface area-, and volume-based measures were extracted and compared in a total of 606 participants, including 132, 165, and 309 in groups of familial ADHD (ADHD-F), non-familial ADHD (ADHD-NF), and typically developed children, respectively. Compared to controls, …

Regulation Of Hedgehog And Wnt Signaling In Neural Differentiation Of P19 Embryonal Carcinoma Cells, Danielle Margaret Spice

Electronic Thesis and Dissertation Repository

The Hedgehog (Hh) and Wnt protein signaling pathways are essential in the differentiation of neurons and astrocytes. As there are many known and new players involved in regulating these pathways, the role of the regulators Suppressor of Fused (SUFU) and Never in Mitosis Kinase 2 (Nek2) have either not been previously reported or have not been thoroughly explored. To address this shortfall CRISPR gene editing was used to target SUFU and Nek2 in the mouse P19 embryonal carcinoma cell model of neural differentiation. Hh and Wnt signaling were explored in normal P19 neural differentiation, which occurs in the presence of …

Using Machine Learning To Identify Neural Mechanisms Underlying The Development Of Cognition In Children And Adolescents With Adhd, Brian Pho

Electronic Thesis and Dissertation Repository

Childhood and adolescence are marked by improvements to cognition and by the emergence of neurodevelopmental disorders such as attention deficit hyperactivity disorder (ADHD). What neural mechanisms are associated with cognitive development in ADHD? In this study, I applied machine learning models to functional connectivity profiles to identify patterns of network connectivity that predict various cognitive abilities in a group of participants ages 6 to 16 with ADHD. The models successfully predicted IQ, visual spatial, verbal comprehension, and fluid reasoning in children ages 6 to 11, but not adolescents. Furthermore, the models identified connections with the default mode, memory retrieval, and …

Role Of Nuclear Lamins In Oligodendrocyte Lineage Cells, Camila Yattah

Dissertations, Theses, and Capstone Projects

Differentiation of oligodendrocytes from progenitor cells is a highly regulated process characterized by a series of molecular changes, resulting in nuclear and morphological features unique to the mature oligodendrocyte state. Heterochromatin formation starting at the nuclear periphery, as well as increased nuclear rigidity are characteristically observed. The nuclear periphery is characterized by the presence of the nuclear lamina and it has been implicated in higher-order genome organization in cells. Lamins are the protein components of the nuclear lamina, and their expression is dependent upon the cell differentiation stage of the cells. While Lamin B1 (LMNB1) expression is high in progenitors …

Clustered Protocadherins Ubiquitination And Phosphorylation Regulates Surface Expression, Albert Ptashnik

Dissertations, Theses, and Capstone Projects

Clustered protocadherins (Pcdhs) are a family of 60 adhesion-like molecules forming a neural barcode. In vertebrate neurons, 60 Pcdhs are coded by a large gene cluster. Numerous axons in the cluster are coding for the different extracellular, transmembrane, variable portion of the cytoplasmic and constant cytoplasmic domains where their expression is controlled epigenetically. These proteins mediate interactions between axons, dendrites, and glial cells during neural development. Yet, Pcdhs are not strictly adhesion molecules. In the amacrine cells of the retina, Pcdhs promote avoidance of the same cell dendrites, where in the cortex Pcdhs promote interactions between dendrites and astrocytes. In …

Dietary Regulation Of Silent Synapses In The Dorsolateral Striatum, Allison M. Meyers

Dissertations, Theses, and Capstone Projects

Obesity and drugs of abuse share overlapping neural circuits and behaviors. Cravings for drugs of abuse increase during abstinence, a phenomenon known as incubation. In obesity, increased craving is observed in individuals during dieting. Diets often fail, with return to- or increase above- original weight. The extent to which this reflects an incubation phenomenon has not been carefully examined. One mechanism underlying incubation is the reemergence of a developmental mechanism called silent synapses. Silent synapses are 'temporary' synapses that are important for remodeling brain circuits. They are prevalent during early development but largely disappear by adulthood. Drugs of abuse increase …

The Effects Of Prenatal Cannabis Exposure On The Basolateral Amygdala, Karen Kw Wong

Undergraduate Student Research Internships Conference

Clinical and preclinical studies indicate prenatal cannabis exposure (PCE) pathologically affects fetal brain development and may increase vulnerability to neuropsychiatric disorders, including schizophrenia and mood/anxiety disorders. In review research from our lab suggests that fetal exposure to Δ9-THC sex-selectively impairs mesocorticolimbic (MCL) circuit function. However, there is a distinct lack of focus on PCE models on the BLA. The BLA plays a central role within the MCL where it directly interacts with the VTA, PFC and HIPP. Importantly, our model exhibits significant VTA hyperdopaminergic activity, and sex-specific alterations to PFC/HIPP glutamate firing, alongside region- and sex-specific changes in dopamine (DA), …

Examining The Relationships Between Socio-Cognitive Factors And Neural Synchrony During Movie Watching Across Development, Kathleen M. Lyons

Electronic Thesis and Dissertation Repository

While different cognitive abilities mature, the conscious experiences of children likely become richer and more elaborate. A challenge in investigating relationships between cognitive development and real-world experiences is having measures that assess naturalistic processing. Movie watching offers a solution, since following the plot of a film requires cognitive processes that are similar to real-world experiences. When different adults watch the same film, their brain activity begins to align (known as neural synchrony). The strength of this alignment has been shown to reflect the degree to which different individuals are having a similar experience of the movie. While this phenomenon has …

Respiratory Morbidity And Neurodevelopmental Outcomes In Infants Born Preterm: A Complex Web, Anna Maria Hibbs

Faculty Scholarship

This commentary is on the original article by Yu et al. on pages 1246–1253 of this issue.

The Effects Of Astrocytic Derived Insulin-Like Growth Factor (Igf-1) On Cognition And Astrocytes, Destiny Wilson

Honors Theses

Insulin-like growth factor 1 (IGF-1) is a neuroendocrine signaling hormone that plays a vital role in growth and development, as well as learning and memory. Inhibition of this hormone results in cognitive impairments like those seen with age-related decline. While a majority of research has focused on the role of IGF-1 on neurons, the role of astrocytes still needs to be explored. Our research investigates how astrocytes and cognition are affected as a result of direct regulation of localized IGF-1 production in early development and after puberty. Preliminary studies in our laboratory established a connection between IGF-1 and glial fibrillary …

Effects Of Storage Conditions On Bpa Leaching From Infant Oral Hygiene Products Using Fluorescence Spectroscopy, Emma Bynum

Honors Theses

Infants are at the highest risk of BPA exposure compared to any other stage of life. Because an infant’s endocrine system is developing, exposure to an endocrine-disruptor, such as BPA, can be especially harmful. Bisphenol-A (BPA) is a structural component in many plastic products, which acts as an endocrine-disruptor mimicking estrogen. This hormonal disruption has been linked to obesity, reproductive issues, cardiovascular problems, and the neurodevelopment disorders. While the FDA monitors things like baby bottles, canned goods, and plastic containers for BPA, infantile oral hygiene products are not closely monitored. Previous research tested infant toothbrushes on the market using a …

Identification Of Dna Methylation Episignatures For Classification And Phenotype/Genotype Correlation In Mendelian Neurodevelopmental Disorders, John Reilly

Electronic Thesis and Dissertation Repository

ABSTRACT: Diagnosis for neurodevelopmental disorders poses numerous challenges, related to the lack of specific findings and limited understanding of clinical impact of the majority of genetic variation. Epigenomics mechanisms involve chemical modifications in DNA that involve a range of cellular mechanisms. DNA methylation is an epigenetic mechanism involving addition and removal of methyl groups to cytosine residues. These methylation signals form episignatures; patterns of methylation that can be used as biomarkers capable of differentiating neurodevelopmental disorders. EpiSigns have enabled molecular diagnosis of a number of genetic conditions, classification of variants of unknown significance, and provided insights into the pathophysiology of …

Self-Conscious Emotions And The Right Fronto-Temporal And Right Temporal Parietal Junction, Adriana Lavarco, Nathira Ahmad, Qiana Archer, Matthew Pardillo, Ray Nunez Castaneda, Anthony Minervini, Julian Keenan

Department of Biology Faculty Scholarship and Creative Works

For more than two decades, research focusing on both clinical and non-clinical populations has suggested a key role for specific regions in the regulation of self-conscious emotions. It is speculated that both the expression and the interpretation of self-conscious emotions are critical in humans for action planning and response, communication, learning, parenting, and most social encounters. Empathy, Guilt, Jealousy, Shame, and Pride are all categorized as self-conscious emotions, all of which are crucial components to one’s sense of self. There has been an abundance of evidence pointing to the right Fronto-Temporal involvement in the integration of cognitive processes underlying the …

Beginnings, Elizabeth Becker

Dance (MFA) Theses

Researcher Elizabeth Becker uses personal experiences of pregnancy alongside scholarly research on the developmental movement patterns of the human embryo, fetus, and newborn’s first year of life to explore the multiplicity of these movement patterns within and outside the womb. Becker explores the relationship between the fertilization, germinal, embryonic, and fetal stages in relation to a newborn and its mother. These movement patterns within the beginning stages of life are valuable to research because they simulate neurodevelopmental patterns, which help wire the central nervous system in early childhood. These movements also help lay the foundation for sensory-motor development and life-long …

Chronic Adolescent Stress As A Predictive Factor For The Risk Of Developing Ptsd-Like Symptoms In Adulthood, Grace K. Young

Theses and Dissertations

Post-traumatic stress disorder is a stress and trauma based psychological disorder that is defined by the DSM-IV as an anxiety disorder that affects approximately 7.8% of people in the United States. PTSD is when those who suffer a traumatic event have intense and distressing feelings, emotions, and memories for a prolonged period of time after the event. A prominent feature of PTSD is the impaired ability to properly extinguish a fear response after a dangerous trigger or stressor is no longer present, also known as safety learning. Stressors are threats perceived within the environment that activate a response within the …

Examining Development And Function Of Pretectal Visual Neural Circuits In Gs Homeobox 1 Mutant Zebrafish, Alexandra Rose Schmidt

Graduate Theses, Dissertations, and Problem Reports

Brain development requires a coordinated genetic code to regulate initial cell identity determination, migration, and connectivity, to establish function of neural circuits. Independent neural circuits underlie our ability to produce both complex and innate behavioral responses to sensory stimuli that are often conserved across vertebrate organisms. Sensory processing disruptions are associated with several neurodevelopmental disorders (NDDs). Therefore, gene mutations altering neurodevelopment can lead to changes influencing structure and function of individual neural circuits, causing behavioral deviations in sensory responsiveness. Crucial gene networks that define functional properties of sensory domains are often explored using non-mammalian vertebrate models, such as the zebrafish. …

The Effects Of D2 Receptor Modulation On Locomotor Development In Danio Rerio, Isaiah Thomas Mcroberts

Senior Projects Spring 2022

This study utilized a novel design to investigate the sensitivity of D2 dopamine receptors to modulating compounds through multiple exposures over early development of zebrafish larvae. Zebrafish were dosed for 30 minutes from 5-8 days post fertilization (dpf) with 16µ/mol of either a D2 antagonist, haloperidol, or a D2 agonist, quinpirole hydrochloride. Two other groups were then dosed with these compounds from 9-12dpf. The effects of D2 receptor modulation were measured by analyzing motor activity on measures of movement distance, frequency, and velocity. Results indicated that larvae dosed with haloperidol on 5dpf had increased activity after the first dosage, but …

Probing The Role Of Astrocytes In The Pathology Of Fragile X Syndrome With Human Stem Cells, Baiyan Ren

Theses & Dissertations

Fragile X syndrome (FXS) is an X-linked neurodevelopmental disorder related to intellectual disability and the most common monogenic cause of autism spectrum disorder. FXS is mainly caused by an expansion of CGG repeats in the 5’-untranslated region of fragile X mental retardation 1 (FMR1) gene, leading to the loss of expression of fragile X mental retardation protein (FMRP). Astrocytes are the most abundant glial cells in the central nervous system (CNS). Loss of FMRP in astrocytes has been found to contribute to structural and functional synaptic deficits in the Fmr1-KO mouse model. The contribution of human astrocytes, however, to the …

Gradient Generating Microfluidic Coculture System For Disease Modeling And Neural Development, Phaneendra Chennampally

Electronic Theses and Dissertations

Cellular microenvironment or cell niche plays an important role in developmental biology and disease pathophysiology. Physical or chemical signals in microenvironment drive the cellular activity. These signaling molecules are generated from the surrounding cells/tissues as part of intercellular communication; a fundamental property of a cell. Dynamic profile of these signaling molecules in the microenvironment plays a pivotal role in transfer of molecular information from cell to cell in disease proliferation or fate determination. Recapitulating these signaling cues in an in vitro study is difficult to achieve using standard cell culture techniques. However microfluidic systems are capable of addressing these issues, …

Modeling Fetal Brain Development: A Semi-Automated Platform For Localization, Reconstruction, And Segmentation Of The Fetal Brain On Mri, Jianan Wang

Electronic Thesis and Dissertation Repository

With advances in fetal magnetic resonance imaging (MRI), research in neonatal neuroscience has shifted to identify in utero brain-based biomarkers for outcome prediction in high-risk fetuses, particularly those impacted by growth restriction. Volumetric segmentation of the fetal brain can provide better understanding of the trajectories of brain development and may aid in predicting functional outcomes. The current thesis aimed to develop semi-automatic methods to target deep brain structures in the fetal brain identified on MR images in fetuses with and without growth restriction. In this study, pregnant women (35-39 weeks gestational age [n=9]) with growth appropriate (n=8) and growth restricted …

The Predictive Influence Of Challenging Behavior On Parent Stress In Young Children With Autism Spectrum Disorder, Paige Weir

LSU Master's Theses

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication, restricted interest, and repetitive patterns of behavior. Individuals with ASD also exhibit challenging behaviors that affect parent and caregiver stress directly. However, researchers have not yet examined the predictive influence of specific challenging behaviors on parent stress, particularly in young children (i.e., infants and toddlers) with ASD. Therefore, the current study expands existing literature by a) investigating the influence that challenging behaviors of young children with ASD have on parent stress and b) examining the unique contribution that each behavior (i.e., aggressive/disruptive behavior, stereotypy, and self-injurious …

The Effects Of Alcohol On The Developing Drosophila Nervous System, Erica E. Hassoun

The Cardinal Edge

Ethanol is the most common human teratogen, contributing to fetal alcohol syndrome (FAS) when effects are the most severe. Key effects of fetal alcohol syndrome are observed in the nervous system. The high prevalence of prenatal alcohol exposure necessitates novel treatment and prevention methods. However, ethical issues prevent researching humans in utero. For this reason, the fruit fly Drosophila melanogaster has emerged as a model organism for studying FAS. Because Drosophila is a small and non-placental organism, its environment can be easily controlled, allowing for specific doses and time periods of ethanol exposure to be studied. This review discusses findings …

Intergenerational Transmission Of Functional Connectivity Profiles In Isolated Reading And Math Networks: A Scoping Review And Study Proposal, Ashini Peiris, Ira Gupta, Lien Peters, Eric D. Wilkey

Undergraduate Student Research Internships Conference

The scoping review surveyed the existing literature on the topic of resting-state functional connectivity (rsFC) and mathematical cognition. The review revealed that rsFC is indicative of distinct long-term developmental trends in mathematical processing, alluding to individual differences in math abilities. Though there have been multiple studies that investigate individual differences in functional connectivity patterns related to math development and math learning disorders, no study has directly investigated to what degree these neurobiological factors are heritable. To address this topic, the following intergenerational transmission (IT) study is proposed. IT is the transfer of personal values, abilities, behaviours, and traits, from parents …

Task-Based And Resting-State Functional Connectivity In Children With Dyscalculia, Ira Gupta

Undergraduate Student Research Internships Conference

Resting-state functional connectivity (RSFC) is a unique method in neuroimaging that measures the spontaneous neural activity as the brain is at rest, not actively undergoing any task. It is important in investigating brain patterns that result from brain regions working together throughout an individual’s development. The application of this technique has been limited in the mathematical cognition field, and thus, should be explored further. This preregistration poster focuses on the depth of the literature and studies available in regards to RSFC and math cognition through a scoping review, and then proposes a study in which task-based and resting-state functional connectivity …

Investigating The Effects Of Maternal Immune Activation On Sensory Processing: Timing, Immune Mechanisms, And Gene-Environment Interactions, Faraj Haddad

Electronic Thesis and Dissertation Repository

Maternal infection during the first or second trimester of pregnancy poses a risk factor for the child to have neurodevelopmental disorders like autism spectrum disorder (ASD) and schizophrenia. Various clinical and preclinical studies have shown that the maternal immune response to infection, also known as maternal immune activation (MIA), can disrupt fetal brain development.

Over the past two decades, MIA has been studied in rodents using the Polyinosinic Polycytidylic acid (Poly I:C) rodent model. Poly I:C has a molecular pattern resembling viruses that can induce a robust immune response. Following exposure to Poly I:C MIA, rodent offspring exhibit many brain …

Having A High-Activity Catechol-O-Methyltransferase Allele Is Associated With Elevated Anxiety And Lower Salivary Dehydroepiandrosterone But Also Lower Alpha Amylase In Children With Chromosome 22q11.2 Deletion Syndrome., Jessie Beebe

University of New Orleans Theses and Dissertations

Chromosome 22q11.2 deletion syndrome (22q11.2DS) results from a hemizygous deletion located on the long arm of chromosome 22. The most common deletion sizes affect between 30 and 90 genes. Individuals with 22q11.2DS may develop serious developmental and psychiatric disorders. The phenotype is highly variable, however, and may be influenced by allelic variation of the retained copies of genes covered by the deletion. I set out to examine the effects of two genes, catechol-O-methyltransferase (COMT) and proline dehydrogenase (PRODH), in relation to anxiety in children and adolescents with 22q11.2DS. Individuals with the major COMT allele (higher activity) have significantly higher anxiety …

Neuronal Migration In Developmental Hyperserotonmia: Assessment Of Vesicular Glutamate In The Raphe Nuclei, Trey M. Shupp

MSU Graduate Theses

The neurotransmitter serotonin is involved in the early development of the central nervous system and the organization of neurons throughout the cerebral cortex and cerebellum. It is proposed that serotonin indirectly interacts with cells in the marginal zone of the cerebral cortex known as Cajal-Retizus (CR) cells. These cells secrete the extracellular matrix protein reelin, which is known for its role in neuronal organization and migration during early neural development. It has been observed that low levels of serotonin are associated with similarly low levels of reelin during development and have been reported to result in disorganization of neurons in …

Biallelic Variants In Pcdhgc4 Cause A Novel Neurodevelopmental Syndrome With Progressive Microcephaly, Seizures, And Joint Anomalies, Maria Iqbal, Reza Maroofian, Büşranur Çavdarlı, Florence Riccardi, Michael Field, Siddharth Banka, Dalal K. Bubshait, Yun Li, Jozef Hertecant, Shahid Mahmood Baig

Department of Biological & Biomedical Sciences

Purpose: We aimed to define a novel autosomal recessive neurodevelopmental disorder, characterize its clinical features, and identify the underlying genetic cause for this condition.
Methods: We performed a detailed clinical characterization of 19 individuals from nine unrelated, consanguineous families with a neurodevelopmental disorder. We used genome/exome sequencing approaches, linkage and cosegregation analyses to identify disease-causing variants, and we performed three-dimensional molecular in silico analysis to predict causality of variants where applicable.
Results: In all affected individuals who presented with a neurodevelopmental syndrome with progressive microcephaly, seizures, and intellectual disability we identified biallelic disease-causing variants in Protocadherin-gamma-C4 (PCDHGC4). Five variants were …