Biology Commons^™

The Role Of Apolipoprotein E In Regulating Tau Pathogenesis And Neurodegeneration In A Tauopathy Mouse Model, Yang Shi

Arts & Sciences Electronic Theses and Dissertations

APOE4 is the strongest genetic risk factor for late-onset Alzheimer's disease (AD). APOE4 increases brain amyloid-β (Aβ) pathology relative to other APOE isoforms. However, whether APOE independently influences tau pathology, the other pathological hallmark of AD and other tauopathies, or tau-mediated neurodegeneration, is not clear. By generating P301S tau transgenic mice on either a human APOE knock in (KI) or APOE knockout (KO) background, we show that the presence of human APOE, regardless of APOE isoforms, leads to various degrees of brain atrophy in 9-month old P301S mice, whereas APOE ablation strongly protects against neurodegeneration. In particular, P301S/E4 mice develop …

The Costs Of A Big Brain: How Region Scaling And Energetic Costs Influence Brain Size Evolution In Weakly Electric African Fishes (Mormyridae), Kimberley Varunee Sukhum

Arts & Sciences Electronic Theses and Dissertations

Brains control an organismճ ability to sense, remember, and respond to the frequently changing world. Brains are composed of multiple regions and systems, which are associated with different processes. These regions are homologous across all vertebrates yet vary greatly in size and shape across clades. While regions can function independently, they also interact extensively. These characteristics make it difficult to predict whether regions can change in size independently from other regions in response to selection (mosaic evolution hypothesis), or whether the brain evolves as a single concerted organ (concerted evolution hypothesis). Further, many traits such as cognition, behavioral flexibility, and …

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 & 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 …

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 …

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 …

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 …

Insights Into The Cyclooxygenase Pathway In A Progressive Rat Model Of Parkinson’S Disease Induced By Prostaglandin J2: Protection With Ibuprofen, Chuhyon Corwin

Dissertations, Theses, and Capstone Projects

Parkinson’s disease (PD) is a neurodegenerative disease with aging as a major risk factor. Its defining symptoms are motor deficits that are primarily associated with dopaminergic neuronal loss in the substantia nigra pars compacta (SNpc) in the midbrain. Post-mortem PD brains exhibit abnormal intraneuronal inclusions of α-synuclein and ubiquitinated protein aggregates known as Lewy bodies, a hallmark of PD pathology.

Currently, there is no validated biomarker for PD. Especially the early stage of PD is difficult to detect as the pathology develops progressively. While symptom-managing treatments are available, there is no neuroprotective treatment as of yet, mainly due to the …

Functional Investigation Of A Brainstem Excitatory Connection Relevant To Sensorimotor Gating, Luis Enrique Martinetti

Open Access Theses & Dissertations

To focus attention, our brain has to "gate" or block irrelevant sensory information that could lead to brain overload. This is done by way of a neuronal pre-attentive mechanism termed sensorimotor gating (SG). Therefore, deficits in the SG mechanism prevent patients from focusing attention. SG deficits have been observed in patients suffering from various neurological disorders, and it is a hallmark of schizophrenia. Previous work has identified key brain areas, such as the pedunculopontine tegmental nucleus (PPTg), that send inputs to the brainstem to regulate SG. However, there is still a knowledge gap concerning what cell types are involved and …

Relationship Of Head Circumference And Epilepsy Severity In Infants With Tuberous Sclerosis Complex, Alexis Levine

Honors Theses

Tuberous sclerosis complex (TSC) is a rare genetic disorder, characterized by high incidence of seizures and tubers (benign cellular abnormalities that appear on brain imaging). Current literature reports an increased head circumference within the TSC population, but the implications, exact rate, or how big the increase is, remains unknown. We hypothesized that increased head circumference would correlate with epilepsy severity in infants with TSC. We examined clinical data from 121 infants diagnosed with TSC who were enrolled in the multi-site, prospective TSC autism center for excellence network (TACERN) study. We calculated each infant’s head circumference z-score from each study visit …

A Comparative Study Of Sleep, Diurnal Patterns, And Eye Closure Between The House Mouse (Mus Musculus) And African Spiny Mouse (Acomys Cahirinus), Chanung Wang

Theses and Dissertations--Biology

To understand the function and origins of sleep, sleep needs to be studied across many different species. Although it is well conserved throughout mammals, 95% of papers are restricted to just three species, Homo sapiens, Mus musculus, and Rattus norvegicus. We aimed to characterize sleep and wake in a Murid rodent Acomys cahirinus in greater detail alongside the well-studied laboratory house mouse (Mus musculus) and wild M. musculus using a well validated, non-invasive, piezoelectric system for sleep and activity monitoring. We confirmed A. cahirinus, M. musculus, and wild M. musculus to be primarily …

Modulation Of Cytokine Signaling In Optic Nerve Regeneration In Xenopus Laevis, Rupa Priscilla Choudhary

Legacy Theses & Dissertations (2009 - 2024)

The axons of the optic nerve, like other central nervous system (CNS) axons, tend to lose their capacity to regenerate following an injury in adult amniotes, but these axons are able to regenerate throughout life in anamniotes. In mammals, optic axon regeneration is promoted by inhibiting the increased expression in retinal ganglion cells of a cytokine signaling molecule, Suppressor of Cytokine Signaling 3 (SOCS3), that accompanies injury. In animals capable of regeneration, SOCS3 mRNA expression also increases dramatically in retinal ganglion cells after optic nerve injury, but somehow this increase is insufficient to block regeneration. To gain insights into how …

Control Of Striatal Activity By Neuronal Glutamate Transporters, Modhurika De

Legacy Theses & Dissertations (2009 - 2024)

The basal ganglia are subcortical nuclei that control the execution of learnt motor behaviors and emotions. The striatum, the main output nucleus of the basal ganglia, receives glutamatergic inputs from the cortex and thalamus and sends GABAergic inputs to the sub-thalamic nucleus via the axonal projections of D1- and D2-receptor (D1R and D2R) expressing medium spiny neurons (D1- and D2-MSNs, respectively). The dorsolateral striatum (DLS) is mainly involved in movement execution, whereas the ventromedial striatum (VMS) regulates emotions. Excitatory inputs onto D1- and D2-MSNs are mediated by post-synaptic ionotropic (GluA, GluN) and metabotropic glutamate receptors (mGluRI). The diffusion distance of …

Effects Of Yoga On The Motor Skills Of A Ten-Year-Old Male With Autism Spectrum Disorder, Amber Schmitt

Senior Honors Theses and Projects

Autism Spectrum Disorder (ASD} is a neurodevelopmental disorder that is typically diagnosed in childhood due to the presence of atypical development, social interactions, and repetitive stereotypical patterns of behavior. The purpose of the present study was to examine the effects of a yoga intervention on a ten-year-old male diagnosed with ASD. It was hypothesized that the yoga intervention on select instructed poses would increase both pose duration and pose performance and that the results would generalize to longer pose duration and better pose performance on non-instructed poses. Pre-intervention assessments of motor functioning were administered, including the Movement ABC, BOT-2, TGMD, …

Intra-Cellular Mechanisms By Which Pac1 Receptor Activation Mediates Stress-Induced Reinstatement To Drug-Seeking, Olivia Miles

Graduate College Dissertations and Theses

The abuse of and addiction to drugs of abuse, such as tobacco, alcohol, opioids, and illicit drugs, are growing global problems that affect the welfare of individuals and societies worldwide. The National Institute of Drug Abuse estimates the annual cost of substance abuse to be over $740 billion in costs related to drug intoxication, withdrawal and relapse. A primary challenge in the treatment of substance abuse is the tendency of users to relapse following acute or extended periods of abstinence; on average over 60% of substance abusers will return to drug use within a year of receiving treatment, many relapsing …