Neuroscience and Neurobiology Commons^™

Molecular Mechanism Of Neurodegeneration Induced By 4-Nonylphenol, Michelle Alejandra Aranda

Open Access Theses & Dissertations

Neurodegeneration, a progressive loss of nerve cells, occurs in many neurological disorders, including Alzheimer's disease (AD) and Parkinson's diseases (PD), as well as in dementia. The pathogenesis of these diseases is unknown, and recent evidence suggests that environmental factors, which act as endocrine-disrupting compounds (EDCs) could play a significant role in developing the disease process. 4-Nonylphenol (4-NP), an EDC, and a ubiquitous environmental toxin has been shown to affect brain development and may cause neurodegeneration. 4-NP is produced in large quantities in the U.S. and used as raw materials for making detergents, pesticides, plastics, paints, cosmetics, rubber, and other industrial/household …

Investigating The Role Of Neuronal Aging In Fragile X-Associated Tremor/Ataxia Syndrome, Katlin Marie Hencak

Honors Undergraduate Theses

Fragile X-associated tremor/ataxia syndrome (FXTAS) is an X-linked late-onset neurodegenerative disorder caused by a noncoding trinucleotide repeat expansion in the FMR1 gene. This gene produces fragile x mental retardation protein (FMRP), an RNA binding protein whose targets are involved in brain development and synaptic plasticity. One of the proposed mechanisms of FXTAS pathogenesis is an RNA gain-of-function in which the repeat expansion causes toxic mRNA that sequesters important proteins in the cell, interfering with their functions. Another suggested method of pathogenesis is through a mutant protein called FMRpolyG. This protein results from repeat-associated non-AUG (RAN) translation, in which the expanded …

Neural Processing Of Communication Signals: The Extent Of Sender–Receiver Matching Varies Across Species Of Apteronotus, Kathryne M. Allen, Gary Marsat

Faculty & Staff Scholarship

As communication signal properties change, through genetic drift or selective pressure, the sensory systems that receive these signals must also adapt to maintain sensitivity and adaptability in an array of contexts. Shedding light on this process helps us to understand how sensory codes are tailored to specific tasks. In a species of weakly electric fish, Apteronotus albifrons, we examined the unique neurophysiological properties that support the encoding of electrosensory communication signals that the animal encounters in social exchanges. We compare our findings to the known coding properties of the closely related species Apteronotus leptorhynchus to establish how these animals …

Relations Among Maternal And Paternal Behavior And Children's Stress Biology, S.K. Jiaming Lin, Stacey N. Doan, John Milton

Scripps Senior Theses

Parenting behavior has been shown to have a wide range of effects, influencing children’s psychological and biological stress outcomes. Most research focuses on maternal parenting behaviors, with few studies observing the effects of paternal behaviors or the influence of both parents on their children. In this study, the relationship between maternal and paternal parenting behaviors was examined in its association to predict children’s cortisol levels. Cultural differences in parenting styles was also observed. American (N=86) and Chinese (N=97) families participated in the study, with parents reporting their behaviors. Children’s cortisol was collected during a stressor task and correlational analysis was …

Shining Light On An Amygdala -- Brainstem Connection Important For Attention Processing, Jose Carlos Cano

Open Access Theses & Dissertations

We are continuously being exposed to an exorbitant amount of sensory information, which should result overwhelming. However, the nervous system operates several intrinsic sensory filtering mechanisms that allow us to cope with such sensory cluttering and shape appropriate behavior. Sensorimotor gating is a pre-attentive neuronal filtering mechanism that gates superfluous sensory information, and orients attentional resources towards salient information processing. Its relevance becomes in individuals suffering from schizophrenia and several otherwise unrelated neuropsychiatric disorders where sensorimotor gating is impaired. To understand the neural impaired mechanisms, extensive research studies have focused on first identifying the neural substrates underlying sensorimotor gating. This …

The Effects Of A Ketone Body On Synaptic Transmission, Alexandra Elizabeth Stanback

Theses and Dissertations--Biology

The ketogenic diet is commonly used to control epilepsy, especially in cases when medications cannot. The diet typically consists of high fat, low carb, and adequate protein and produces a metabolite called acetoacetate. Seizure activity is characterized by glutamate excitotoxicity and therefore glutamate regulation is a point of research for control of these disorders. Acetoacetate is heavily implicated as the primary molecule responsible for decreasing glutamate in the synapse; it is believed that acetoacetate interferes with the transport of glutamate into the synaptic vesicles. The effects on synaptic transmission at glutamatergic synapses was studied in relation to the ketogenic diet …

Sodium Channel Distribution In The Apical Dendrites Of Pyramidal Cells Vary In The Hindbrain Of Apteronotus Leptorhynchus., Sree Indrani Motipally

Graduate Theses, Dissertations, and Problem Reports (ETD)

Apteronotid weakly electric fish heavily rely on their electrosensory system for behaviors like spatial navigation, communication and prey capture. Since the behaviorally important information about their environment is contained in the spatial and temporal modulations of the electrosensory signal, efficient mechanisms to process this information with great fidelity are of the utmost importance. Efficient sensory processing often involves having multiple parallel processing streams so that each stream can specialize to treat signals with different properties. This strategy requires the response properties and neural dynamic to be adjusted in each pathway to implement different neural coding strategies. One of the neural …

Polyglutamine Repeat Proteins Disrupt Actin Structure In Drosophila Photoreceptors., Annie Vu, Tyler Humphries, Sean Vogel, Adam Haberman

Biology: Faculty Scholarship

Expansions of polygutamine-encoding stretches in several genes cause neurodegenerative disorders including Huntington's Disease and Spinocerebellar Ataxia type 3. Expression of the human disease alleles in Drosophila melanogaster neurons recapitulates cellular features of these disorders, and has therefore been used to model the cell biology of these diseases. Here, we show that polyglutamine disease alleles expressed in Drosophila photoreceptors disrupt actin structure at rhabdomeres, as other groups have shown they do in Drosophila and mammalian dendrites. We show this actin regulatory pathway works through the small G protein Rac and the actin nucleating protein Form3. We also find that Form3 has …

Cell Specific Control Of The Pallidostriatal Pathway, Shubha Verma '19

Student Publications & Research

Parkinson’s Disease is a neurodegenerative disorder of the basal ganglia. The main cause for Parkinson’s Disease is the depletion of dopamine, a neurotransmitter. The basal ganglia contains four major nuclei: the substantia nigra, the subthalamic nucleus, the external globus pallidus, and the striatum. These nuclei communicate with each other by the use of neurons.

Crispr Knockouts Reveal An Endogenous Role For Ancient Neuropeptides In Regulating Developmental Timing In A Sea Anemone, Nagayasu Nakanishi, Mark Q. Martindale

Biological Sciences Faculty Publications and Presentations

Neuropeptides are evolutionarily ancient peptide hormones of the nervous and neuroendocrine systems, and are thought to have regulated metamorphosis in early animal ancestors. In particular, the deeply conserved Wamide family of neuropeptides—shared across Bilateria (e.g. insects and worms) and its sister group Cnidaria (e.g. jellyfishes and corals)—has been implicated in mediating life-cycle transitions, yet their endogenous roles remain poorly understood. By using CRISPR-Cas9-mediated reverse genetics, we show that cnidarian Wamide—referred to as GLWamide—regulates the timing of life cycle transition in the sea anemone cnidarian Nematostella vectensis. We find that mutant planula larvae lacking GLWamides transform into morphologically normal polyps …

Genome-Wide Association Study For Variants That Modulate Relationships Between Cerebrospinal Fluid Amyloid-Beta 42, Tau, And P-Tau Levels, Taylor J. Maxwell, Chris Corcoran, Jorge L. Del-Aguila, John P. Budde, Yuetiva Deming, Carlos Cruchaga, Alison M. Goate, John S. K. Kauwe, Alzheimer's Disease Neuroimaging Initiative

Mathematics and Statistics Faculty Publications

Background: A relationship quantitative trait locus exists when the correlation between multiple traits varies by genotype for that locus. Relationship quantitative trait loci (rQTL) are often involved in gene-by-gene (G×G) interactions or gene-by-environmental interactions, making them a powerful tool for detecting G×G.

Methods: We performed genome-wide association studies to identify rQTL between tau and Aβ42 and ptau and Aβ42 with over 3000 individuals using age, gender, series, APOE ε2, APOE ε4, and two principal components for population structure as covariates. Each significant rQTL was separately screened for interactions with other loci for each trait in the rQTL model. Parametric bootstrapping …

Targeting Pro-Inflammatory Function Of Microglia Using Small Molecules To Combat Neurodegeneration, Gabrielle C. Williams, Priya Prakash, Gaurav Chopra

The Summer Undergraduate Research Fellowship (SURF) Symposium

Microglia are the brain’s resident immune cells that are responsible for maintaining homeostasis in healthy conditions. During injury or infection, resting microglia get activated and produce pro-inflammatory cytokines such as IL-1b, IL-1a, IL-6, etc. along with reactive oxygen species like nitric oxide (NO) to combat neuroinflammatory diseases such as Alzheimer’s disease (AD). Inflammation is characterized by the activation of resident-immune cells in the brain called microglia that respond to the eat-me signals released by the toxic amyloid beta peptides as well as the dying neurons in the microenvironment. Recent studies have shown that activated microglia induce neuronal death by secreting …

Characterization Of Theranostic Peptides For Glioblastoma Multiforme, Aaron Mellesmoen

All NMU Master's Theses

Glioblastoma multiforme (GBM) is a type of primary CNS tumor in which viable treatment options do not exist. Standard of care including tumor resection, chemotherapy, and radiation does little to extend the 5-year survival expectancy past 5.1%. Herein, two small-peptide molecules with inherent antitumor activity, blood-brain barrier permeability, and capability for tumor-specific drug deliverance and intraoperative visualization (termed theranostic) were of focus. Confocal microscopy was employed to characterize in vitro specificity of chlorotoxin, a 4 kDa scorpion venom peptide, and rBSG, the recombinant 25 kDa non-glycosylated extracellular domain of extracellular matrix metalloproteinase inducer (EMMPRIN; Basigin) isoform …

The Role Of Perivascular Fibrosis In Post-Stroke Glymphatic Impairment And Cerebral Amyloid Angiopathy, Matthew D. Howe

Dissertations and Theses (Open Access)

In healthy brain tissue, toxic amyloid-β (Aβ) proteins are transported by the pulsatile flow of cerebrospinal fluid (CSF) along perivascular drainage pathways. Ischemic stroke may disrupt this process, leading to a perivascular build-up of Aβ, termed cerebral amyloid angiopathy (CAA). I hypothesize that an abnormal pattern of extracellular matrix deposition within the vascular basement membrane, termed fibrosis, impairs Aβ drainage from the aged brain after stroke. I further hypothesize that inhibition of astrocytic transforming growth factor-β (TGF-β) signaling can reverse these phenotypes. Finally, I also hypothesize that serum biomarkers of perivascular fibrosis can be used to diagnose CAA following intracerebral …

Modeling And Mapping Addiction In The Zebrafish, Danio Rerio, Bradley Serpa

Master of Science in Integrative Biology Theses

Driven by the communication of dopamine, the vertebrate reward system has been evolutionarily conserved to maintain survival and optimize fitness. The neural circuits governing this system integrate sensory stimuli to produce appropriate, self-preserving responses that underlie experience-based learning. In the most primitive vertebrates, dopamine release in neuronal circuits drives homeostatic behaviors, such as seeking nutrients, finding a mate, or avoiding danger. From agnathans to mammals, dopaminergic synthesis and signaling genes and molecules, along with neuronal pathways and reward system-based behaviors, remain highly conserved. Dopamine signaling proteins include two classes of metabotropic G-Protein Receptor Coupled Dopamine Receptors, D1-like (DRD1) and D2-like …

Mapping Molecular Datasets Back To The Brain Regions They Are Extracted From: Remembering The Native Countries Of Hypothalamic Expatriates And Refugees, Arshad Khan, Alice Grant, Anais Martinez, Gully Burns, Brendan Thatcher, Vishwanath Anekonda, Benjamin Thompson, Zachary Roberts, Daniel Moralejo, James Blevins

Selected Works Temporary Series

This article, which includes novel unpublished data along with commentary and analysis,focuses on approaches to link transcriptomic, proteomic, and peptidomic datasets mined frombrain tissue to the original locations within the brain that they are derived from using digital atlasmapping techniques. We use, as an example, the transcriptomic, proteomic and peptidomicanalyses conducted in the mammalian hypothalamus. Following a brief historical overview, wehighlight studies that have mined biochemical and molecular information from the hypothalamusand then lay out a strategy for how these data can be linked spatially to the mapped locations in acanonical brain atlas where the data come from, thereby allowing …

Mapping Molecular Datasets Back To The Brain Regions They Are Extracted From: Remembering The Native Countries Of Hypothalamic Expatriates And Refugees, Khan, Alice Grant, Anais Martinez, Gully Burns, Brendan Thatcher, Vishwanath Anekonda, Benjamin Thompson, Zachary Roberts, Daniel Moralejo, James Blevins

Departmental Papers (Biology)

This article, which includes novel unpublished data along with commentary and analysis,focuses on approaches to link transcriptomic, proteomic, and peptidomic datasets mined frombrain tissue to the original locations within the brain that they are derived from using digital atlasmapping techniques. We use, as an example, the transcriptomic, proteomic and peptidomicanalyses conducted in the mammalian hypothalamus. Following a brief historical overview, wehighlight studies that have mined biochemical and molecular information from the hypothalamusand then lay out a strategy for how these data can be linked spatially to the mapped locations in acanonical brain atlas where the data come from, thereby allowing …

Reflections On Contributing To “Big Discoveries” About The Fly Clock: Our Fortunate Paths As Post-Docs With 2017 Nobel Laureates Jeff Hall, Michael Rosbash, And Mike Young, Kathleen King Siwicki, P. E. Hardin, J. L. Price

Biology Faculty Works

In the early 1980s Jeff Hall and Michael Rosbash at Brandeis University and Mike Young at Rockefeller University set out to isolate the period (per) gene, which was recovered in a revolutionary genetic screen by Ron Konopka and Seymour Benzer for mutants that altered circadian behavioral rhythms. Over the next 15 years the Hall, Rosbash and Young labs made a series of groundbreaking discoveries that defined the molecular timekeeping mechanism and formed the basis for them being awarded the 2017 Nobel Prize in Physiology or Medicine. Here the authors recount their experiences as post-docs in the Hall, Rosbash and Young …

Muscle Synergies And How They Contribute To The Movement Of The Tail During The Nociceptive Withdrawal Response In The Rat’S Tail, Hasti Izadpanah

Senior Honors Projects, 2010-2019

Noxious stimuli can evoke the nociceptive withdrawal response (NWR), which protects the affected part of the body from injury. The rat’s tail, because of the large number of joint (n=84) and muscle (n=300) degrees of freedom, may present a computational challenge to the central nervous system. Previous studies have revealed that synergies act to reduce the number of degrees of freedom across diverse movements in a variety of animals; however, there is little information in mammals on synergistic control of the tail. The long-term specific aim of this project is to test the hypothesis that during the NWR muscle synergies …

The Role Of Oxidative Stress And Signal Transduction In Chemotherapy-Mediated Cognitive Impairment In The Menopause Rat Model, Ciara Bagnall

Dissertations, Theses, and Capstone Projects

Systemic chemotherapy treatment is associated with long-term cognitive impairment in breast cancer survivors. While many studies have established the forms of cognition and corresponding regions in the brain most affected, very little is revealed about the potential molecular mechanisms that mediate these changes. The effects of systemic treatment on the brain is likely attributed to many different mechanisms including oxidative stress and immune dysregulation. Earlier studies from our lab have investigated the effects of the chemotherapy cocktail doxorubicin and cyclophosphamide (AC Chemotherapy) in an ovariectomized menopause animal model of ‘chemo brain’ (Salas-Ramirez et al., 2015). We observed that animals injected …

Spinal Cord Trauma: An Overview Of Normal Structure And Function, Primary And Secondary Mechanisms Of Injury, And Emerging Treatment Modalities, Daniel Morin

Senior Honors Theses

The structures of the spinal cord and vertebral column are designed to provide flexibility, while still providing ample protection for the spinal cord deep within. While it does offer remarkable protection against most routine trauma, the spinal cord is still vulnerable to high-force etiologies of trauma and may become damaged as a result. These events are referred to as primary injury. Following the initial injury, the body’s own physiological responses cause a cascade of deleterious effects, known as secondary injury. Secondary injury is a major therapeutic target in mitigating the effects of spinal cord injury (SCI), and much research is …

A Role Of Vitamin B2 In Reducing Amyloid-Beta Toxicity In A Caenorhabditis Elegans Alzheimer’S Disease Model, Muhammad Tukur Ameen

Electronic Theses and Dissertations

Alzheimer’s disease (AD) is associated with amyloid-beta peptide deposition and loss of mitochondrial function. Using a transgenic C. elegans AD worm model expressing amyloid-beta in body wall muscle, we determined that supplementation with either of the forms of vitamin B₂, flavin mononucleotide (FMN) or flavin adenine dinucleotide (FAD) protected against amyloid-beta mediated paralysis. FMN and FAD were then assayed to determine effects on ATP, oxygen consumption, and reactive oxygen species (ROS) with these compounds not significantly improving any of these mitochondrial bioenergetic functions. Knockdown of the daf-16/FOXO transcriptional regulator or the FAD synthase enzyme completely abrogated the …

Killi-Data News (Winter), Tyrone Genade

Killifish Research Review

Valued readers, it is with a heavy heart that I inform you that this is the last issue of Killi-Data News. The good news is that we will be back as Killifish Research Review. The dissolution of Killi-Data International created a prob- lem: how can the newsletter of a defunct organization live on without that organization? But other additional problems were building in the background. The first issue numbered 15 pages. The previous issue was 28 pages. The number of killifish related papers is increasing while time on our end (the editorial team) is running out. It takes a lot …

Killi-Data News (Fall), Tyrone Genade

Killifish Research Review

Many interesting papers have been published over the last three months. The large volume of papers coupled with the start of the new college semester (and the workload it brings) delayed this issue of Killi-Data News. But better late than never—or so I hope! In this issue Richard van der Laan provides an insightful review of the recent Aphanius papers as to their taxonomic implications and questions. The systematic issues he raises show the importance of the Molecular project: we need to get more samples of the various cyprinodontiforme families to resolve unsettled systematic and taxonomic issues. In the Next …

Killi-Data News (Summer), Tyrone Genade

Killifish Research Review

Over the last three months several interesting and exciting pa- pers have been published. By now most of you have heard the Nothobranchius fish poo news emanating from the Valenzano lab. That paper is reviewed and certainly has repercussions for the health of our captive fish. Polaçik et al have published interesting data with ramifications as to how we breed and incubate annual killifish. The big news in this issue is the paper from the Reznick lab which Jean Huber reviews. The contents of that paper goes to the heart of the question of just what a killifish is. The …

Killi-Data News (Spring), Tyrone Genade

Killifish Research Review

This is the start of Killi-Data News’ second year. In this first issue of the year we have the usual review of research pub- lications as well as input from Martin Reichard on his lab’s Nothobranchius research. Martin is responding to my reviews of his lab’s work in the previous edition. I am serious about making sure the content in this newsletter is reliable but I erred in the previous edition and Martin has written extensively to correct my mistake in the section “Erratum”. This reply is welcomed and owed to readers. I must confess that I don’t know everything …

Killi-Data News (Winter), Tyrone Genade

Killifish Research Review

This is the fourth edition, and concluding issue of the first volume, of Killi-Data News and I am happy that it has been well received by readers. At 25 pages this issue is a bit thin- ner than the last but this is because we agreed to make the cut-off for submissions the 1 st of December so we could get this edition out by the New Year. This is an exciting edition full of new species descrip- tions and analyses that will keep taxonomists busy for years to come. Costa has given us two molecular phylogenies on Melanorivulus as …

Killi-Data News (Spring), Tyrone Genade

Killifish Research Review

This is the start of Killi-Data News’ second year. In this first issue of the year we have the usual review of research pub- lications as well as input from Martin Reichard on his lab’s Nothobranchius research. Martin is responding to my reviews of his lab’s work in the previous edition. I am serious about making sure the content in this newsletter is reliable but I erred in the previous edition and Martin has written extensively to correct my mistake in the section “Erratum”. This reply is welcomed and owed to readers. I must confess that I don’t know everything …

A Combinatorial Premotor Neural Code: Transformation Of Sensory Information Into Meaningful Rhythmic Motor Output By A Network Of Heterogeneous Modulatory Neurons, Christopher John Goldsmith

Theses and Dissertations

The goal of the following research was to investigate the contributions of neural networks in selecting distinct variants of rhythmic motor activity. We used the premotor commissural ganglion (CoG) in the stomatogastric nervous system of the Jonah crab to understand how this network effectively controls the rhythms produced in downstream motor circuits. Prior research determined that individual CoG neurons are necessary to mediate sensory-induced variation in the effected motor patterns. However, single premotor neuron inputs to the STG are not sufficient to recreate the patterns induced by the selective activation of sensory pathways. Thus, it was hypothesized that the CoG-mediated …

The Premammillary Nucleus Of The Hypothalamus Is Not Necessary For Photoperiodic Timekeeping In Female Turkeys (Meleagris Gallopavo), Ashli F. Moore, Vincent M. Cassone, Kevin D. Alloway, Paul A. Bartell

Biology Faculty Publications

In birds, seasonal reproduction is regulated by day length, with long days in the spring activating the hypothalamic-pituitary-gonadal axis and reproductive behaviors. The photoreceptors mediating this process remain unknown, but recently, the premammillary nucleus (PMM) of the hypothalamus has been implicated as the site of photoperiodic signaling in turkeys. We performed electrolytic lesions of the PMM to elucidate its role in the photoactivation and maintenance of egg production in female turkeys. Our results show that ablation of the PMM does not alter the normal lay cycle. No differences were found between lesioned birds and sham controls in the latency to …