Neuroscience and Neurobiology Commons^™

Spirituality As A Moderator Between Ptss And Cardiovascular Reactivity, Kriti Sharda

Honors Scholar Theses

Posttraumatic stress symptoms (PTSS) can be distressing and produce robust cardiovascular symptoms, such as increased heart rate and blood pressure, which have been implicated in higher risk of developing cardiovascular disease (CVD). Identifying factors that may reduce symptoms may suggest therapeutic strategies. One such potential factor is spirituality, given that spirituality is associated with both reducing PTSS and with preventing or improving CVD. We sampled 63 young college women who indicated being exposed to unwanted sexual contact. We asked them to write about their experience while we took heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP) …

A Two-Clone Approach To Study Signaling Interactions Among Neuronal Cells In A Pre-Clinical Alzheimer’S Disease Model, Catherine J. Yeates, Ankita Sarkar, Prajakta Deshpande, Madhuri Kango-Singh, Amit Singh

Biology Faculty Publications

To understand the progression of Alzheimer's disease, studies often rely on ectopic expression of amyloid-beta 42 (Aβ42) throughout an entire tissue. Uniform ectopic expression of Aβ42 may obscure cell-cell interactions that contribute to the progression of the disease. We developed a two-clone system to study the signaling cross talk between GFP-labeled clones of Aβ42-expressing neurons and wild-type neurons simultaneously generated from the same progenitor cell by a single recombination event. Surprisingly, wild-type clones are reduced in size as compared with Aβ42-producing clones. We found that wild-type cells are eliminated by the induction of cell death. Furthermore, aberrant activation of c-Jun-N-terminal …

The Nature Of Genes Expressed Differently After Environmental Drug Exposure, Nicci Siffel

Scholars Week

The Nature of Genes Expressed Differently after Environmental Drug Exposure

N. Siffel, S. Anderson, B. Subedi, D.R. Hammond-Weinberger

Drug use, of prescription or illicit varieties, alter bodily functions in different ways, especially in the nervous system. These drugs are found in sources of drinking water because they are not removed by wastewater treatment facilities. To investigate the effects of these drugs as they appear in mixtures, we exposed groups of zebrafish embryos to cocktails of drugs and screened for genes that were differentially expressed between the experimental and control groups and could thus give more insight into their biological functions. …

Axonal Blockage With Microscopic Magnetic Stimulation, Hui Ye

Biology: Faculty Publications and Other Works

Numerous neurological dysfunctions are characterized by undesirable nerve activity. By providing reversible nerve blockage, electric stimulation with an implanted electrode holds promise in the treatment of these conditions. However, there are several limitations to its application, including poor bio-compatibility and decreased efficacy during chronic implantation. A magnetic coil of miniature size can mitigate some of these problems, by coating it with biocompatible material for chronic implantation. However, it is unknown if miniature coils could be effective in axonal blockage and, if so, what the underlying mechanisms are. Here we demonstrate that a submillimeter magnetic coil can reversibly block action potentials …

Ubc-9 Acts In Gaba Neurons To Control Neuromuscular Signaling In C. Elegans, Victoria A. Kreyden, Elly B. Mawi, Jennifer Kowalski

Scholarship and Professional Work - LAS

Regulation of excitatory to inhibitory signaling balance is essential to nervous system health and is maintained by numerous enzyme systems that modulate the activity, localization, and abundance of synaptic proteins. SUMOylation is a key post-translational regulator of protein function in diverse cells, including neurons. There, its role in regulating synaptic transmission through pre- and postsynaptic effects has been shown primarily at glutamatergic central nervous system synapses, where the sole SUMO-conjugating enzyme Ubc9 is a critical player. However, whether Ubc9 functions globally at other synapses, including inhibitory synapses, has not been explored. Here, we investigated the role of UBC-9 and the …

Functions Of Fibroblast Growth Factor Homologous Factor 2 In Excitable Tissues, Christopher Marra

Dissertations, Theses, and Capstone Projects

Purpose: Fibroblast Growth Factor Homologous Factors (FHFs) are a group of proteins known to associate with and modulate voltage-gated sodium channels (Na_v) in excitable cells. The four FHF genes are differentially expressed in specific cell-types, with FHF2 expressed prominently in the hippocampus, cerebral cortex, heart and dorsal root ganglia. Due to previous unavailability of an Fhf2 knockout mouse, this gene’s functions have been understudied in comparison to other those encoding other FHFs. The purpose of this research has been to better understand the normal physiological functions of FHF2 at the cellular and system levels in the heart, sensory …

Employing High Probability Gene Choice Elements To Understand Singular Odorant Receptor Expression, Raena Mina

Dissertations, Theses, and Capstone Projects

The ability to detect odorous chemicals in the environment is the oldest of the senses necessary for survival, from escaping danger, finding mates, to locating food. It is said that humans can identify and discriminate up to a trillion different odor mixtures. For chemoreception to have such a high discriminatory power, would require a diverse population of cells dedicated for odor detection. These detector cells are the olfactory sensory neurons (OSNs), which express odorant receptors (ORs) that bind to chemical odors in the environment. In order to increase specificity and sensitivity, an essential property in olfaction is for each OSN …

The Effects Of Adolescent Chronic Mild Stress: In Female Wistar-Kyoto Rats, Anna Hallowell

The Journal of Purdue Undergraduate Research

Despite years of research to understand under-lying mechanisms and develop more effective treatment approaches for mood disorders, numerous challenges exist. Many chronic stress models are used to study mood disorders, how-ever the majority have been established with adult males. This is problematic considering that affective disorders are more common in women, and generally develop during late adolescence. Studies have indicated fundamental behavioral, physiological, and neural differences between males and females in response to the same external stressors, furthering a need to develop sex-specific paradigms to accurately model the etiology of mood disorders in females. The Wistar-Kyoto (WKY) rat strain is …

Preliminary Evidence Of The Role Of Medial Prefrontal Cortex In Self-Enhancement: A Transcranial Magnetic Stimulation Study, Birgitta Taylor-Lillquist, Vivek Kanpa, Maya Crawford, Mehdi El Filali, Julia Oakes, Alex Jonasz, Amanda Disney, Julian Keenan

Department of Biology Faculty Scholarship and Creative Works

Humans employ a number of strategies to improve their position in their given social hierarchy. Overclaiming involves presenting oneself as having more knowledge than one actually possesses, and it is typically invoked to increase one’s social standing. If increased expectations to possess knowledge is a perceived social pressure, such expectations should increase bouts of overclaiming. As the medial prefrontal cortex (MPFC) is sensitive to social pressure and disruption of the MPFC leads to decreases in overclaiming, we predicted that transcranial magnetic stimulation (TMS) applied to the MPFC would reduce overclaiming and the effects would be enhanced in the presence of …

Transcriptome Analyses In Bv2 Microglial Cells Following Treatment With Amino-Terminal Fragments Of Apolipoprotein E, Tanner B. Pollock, Giovan N. Cholico, Tarun Suresh, Erica S. Stewart, Madyson M. Mccarthy, Troy T. Rohn

Biology Faculty Publications and Presentations

Despite the fact that harboring the apolipoprotein E4 (APOE4) allele represents the single greatest risk factor for late-onset Alzheimer’s disease (AD), the exact mechanism by which ApoE4 contributes to disease progression remains unknown. Recently, we demonstrated that a 151 amino-terminal fragment of ApoE4 (nApoE4_1–151) localizes within the nucleus of microglia in the human AD brain and traffics to the nucleus causing toxicity in BV2 microglia cells. In the present study, we examined in detail what genes may be affected following treatment by nApoE4_1–151. Transcriptome analyses in BV2 microglial cells following sublethal treatment with nApoE4 …

Wild Mice With Different Social Network Sizes Vary In Brain Gene Expression, Patricia C. Lopes, Barbara König

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Background

Appropriate social interactions influence animal fitness by impacting several processes, such as mating, territory defense, and offspring care. Many studies shedding light on the neurobiological underpinnings of social behavior have focused on nonapeptides (vasopressin, oxytocin, and homologues) and on sexual or parent-offspring interactions. Furthermore, animals have been studied under artificial laboratory conditions, where the consequences of behavioral responses may not be as critical as when expressed under natural environments, therefore obscuring certain physiological responses. We used automated recording of social interactions of wild house mice outside of the breeding season to detect individuals at both tails of a distribution …

Her9/Hes4 Is Required For Retinal Photoreceptor Development, Maintenance, And Survival, Cagney E. Coomer, Stephen G. Wilson, Kayla F. Titialii-Torres, Jessica D. Bills, Laura A. Krueger, Rebecca A. Petersen, Evelyn M. Turnbaugh, Eden L. Janesch, Ann C. Morris

Biology Faculty Publications

The intrinsic and extrinsic factors that regulate vertebrate photoreceptor specification and differentiation are complex, and our understanding of all the players is far from complete. Her9, the zebrafish ortholog of human HES4, is a basic helix-loop-helix-orange transcriptional repressor that regulates neurogenesis in several developmental contexts. We have previously shown that her9 is upregulated during chronic rod photoreceptor degeneration and regeneration in adult zebrafish, but little is known about the role of her9 during retinal development. To better understand the function of Her9 in the retina, we generated zebrafish her9 CRISPR mutants. Her9 homozygous mutants displayed striking retinal phenotypes, including decreased …

The Roles Of Inhibition In C. Elegans Locomotion, Lan Deng

Dissertations

Inhibition plays important roles in modulating neural activities at different levels from small synapses to brain regions, and different systems from sensory to motor. To achieve translocation, locomotor systems produce alternation of antagonist muscles, including axial posture and limb movement and alternation. In the nematode C. elegans, a cross-inhibition circuit, involving excitatory cholinergic and inhibitory GABAergic motoneurons, is believed to generate the dorsoventral alternation of body-wall muscles that supports backward undulatory locomotion. This dissertation challenges this prevalent hypothesis, delves into studying different roles of inhibition, and depicts the expression pattern and functional role of ionotropic GABAA receptor, UNC-49, in motoneurons …

Kcnq2 Localization In The Brainstem, Christina Valera

Honors Scholar Theses

KCNQ2 channels are potassium channels that serve to control neuronal excitability. Loss of function mutations in these channels are known to cause various forms of epilepsy. Recently, KCNQ2 R201C and R201H gain of function mutations have been shown to exhibit an exaggerated startle response and other unique phenotypes uncharacteristic of epilepsy. These phenotypes resemble hyperekplexia, a condition in which glycine neurotransmission in the spinal cord and brainstem is affected. While KCNQ2 has widespread localization throughout the brain, its presence in the brainstem remains unknown. We used immunostaining to determine the localization of KCNQ2 in the vagus nerve and hypoglossal nerve …

Cytotoxic Analysis Of Old Drugs: New Drugs For Alzheimer’S Disease, Sebastian Yumiseba

Theses and Dissertations

Microglia are the resident immune cells of the CNS and constitute about 10% of all cells in the CNS. They have a vital role in Alzheimer’s pathogenesis as either cytotoxic or neuroprotective. Recent efforts are being put into repurposing drugs to target the microglia to treat Alzheimer’s disease.

The Role Of Apolipoprotein E In Alzheimer Disease: From Therapy To Mechanism, Tien-Phat Vuong Huynh

Arts & Sciences Electronic Theses and Dissertations

Alzheimer’s disease (AD) is a neurodegenerative disorder associated with irreversible damage to the brain, which manifests in cognitive dysfunction, memory loss, and eventual death. The pathological hallmarks of AD are amyloid plaques, which are cerebral aggregates consisting of fibrils of the amyloid β-protein (Aβ), and filamentous lesions of the microtubule-associated protein tau known as neurofibrillary tangles. In the early 1990s, the apolipoprotein E (apoE) was found to co-localize with amyloid plaques. The ε4 allele of the APOE gene was sequentially identified as the strongest genetic risk factor for AD, increasing the risk by 4 – 12-fold, whereas the ε2 allele …

Sexually Dimorphic Alterations In Brain Morphology Of Astrocyte Conditional System Xc- Knockout Mice, Gabrielle Emily Samulewicz

Biology - All Scholarship

Astrocytes play a vital role in orchestrating the precise brain wiring that occurs during development and are essential for maintaining homeostasis into adulthood. The cystine/glutamate antiporter, system xc-, in the central nervous system is especially abundant in astrocytes and itself is known to contribute importantly to the basal extracellular glutamate concentration as well as the intracellular and extracellular glutathione levels, either of which, if perturbed, could alter brain development and/or contribute to degeneration. Thus, to determine whether loss of astrocyte system xc- might alter brain morphology, I studied a conditional astrocyte system xc- knockout mouse (AcKO). Tissue was harvested from …

Sexually Dimorphic Alterations In Brain Morphology Of Astrocyte Conditional System Xc- Knockout Mice, Gabrielle Emily Samulewicz

Honors Capstone Projects - All

Astrocytes play a vital role in orchestrating the precise brain wiring that occurs during development and are essential for maintaining homeostasis into adulthood. The cystine/glutamate antiporter, system xc-, in the central nervous system is especially abundant in astrocytes and itself is known to contribute importantly to the basal extracellular glutamate concentration as well as the intracellular and extracellular glutathione levels, either of which, if perturbed, could alter brain development and/or contribute to degeneration. Thus, to determine whether loss of astrocyte system xc- might alter brain morphology, I studied a conditional astrocyte system xc- knockout mouse (AcKO). Tissue was harvested from …

Microglia-Neuron Interactions In A Mouse Model Of Low Grade Neuroepithelial Tumors, Veolette Hanna

Honors Scholar Theses

Microglia are the macrophages of the brain and spinal cord, playing an important role in the immune response to disease states of the nervous system. This study conducts an investigation on the activity of microglia in response to low grade neuroepithelial tumors. Using mouse models and microglial markers, a qualitative and quantitative analysis of microglia activation, migration, and invasion within the brain cortex during early stages of tumor development was conducted. It was found that the presence of a low grade neuroepithelial tumor in the cortex of one hemisphere of the brain causes significant microglia activation in comparison to the …

The Effects Of The Atypical Dopamine Uptake Inhibitor Ce-158 On Extracellular Dopamine In The Nucleus Accumbens, Julia Neri

Honors Scholar Theses

Major Depressive Disorder (MDD) is characterized by symptoms such as cognitive dysfunctions, inflammatory changes, and motivational symptoms such as amotivation, fatigue, and anergia. While depressed people are commonly treated by traditional antidepressants such as serotonin reuptake inhibitors (SSRIs), previous studies have reported that SSRI medications do not treat fatigue and anergia symptoms well, and in some cases, can even worsen those symptoms. Subjects treated with dopamine (DA) uptake inhibitors, on the other hand, have been less likely to report symptoms of anergia and fatigue compared to those treated with SSRIs. Common DA uptake inhibitors such as methylphenidate and amphetamines, however, …

Effects Of Alpha- And Beta-Adrenergic Receptor Blockade Upon Inflammatory Responses To Acute And Chronic Sleep Fragmentation, Nicholas David Wheeler

Masters Theses & Specialist Projects

Generally, sleep is viewed as a recuperative process and its dysregulation has

cognitive, metabolic, immunological, and inflammatory implications that are largely deleterious to human health. Epidemiological and empirical studies have suggested that sleep fragmentation (SF) as result of obstructive sleep apnea (OSA) and other sleep abnormalities leads to pronounced systemic inflammatory responses, which are influenced by the sympathetic nervous system (SNS). However, the underlying molecular mechanisms contributing to SNS regulation of SF-induced inflammatory states are not fully understood. To assess the effects of the SNS system, C57BL/6j female mice were placed in automated SF chambers (12L:12D) and subjected to either …

The Effects Of A New Mutation In Lis1 And Its Potential Role In Autism Spectrum Disorder, John A. Slovensky

Senior Theses

LIS1 is a protein, particularly concentrated in the brain, that is important in regulating the movement and transport capabilities of dynein. Dynein is protein that can move along pathways in the cell, carrying various cellular components and also helping brain cells migrate. These two proteins are crucial during the development of the nervous system, and mutations in them can lead to lissencephaly, a disorder in which the brain does not form properly. This disease causes patients to develop cognitive-motor defects and seizures that can lead to early death. While all previously identified mutations in LIS1 are known to cause lissencephaly, …

Amino Acid Sensing Ability By The Mechanistic Target Of Rapamycin In Oligodendrocytes, Emma England

Senior Theses and Projects

Oligodendrocytes (OLs) are a type of glial cell in the central nervous system that require substantial nutrients such as lipids and amino acids to create the extensive, metabolically expensive myelin sheath surrounding the axons of neurons. The mammalian target of rapamycin (mTOR) is a regulatory kinase that is necessary for the maturation of progenitor OLs through their distinct oligo-lineage phases. Amino acids are vital for the functioning of cells. The focus of this study was to determine if mTOR activity is dependent on the availability of leucine, methionine, and alanine. This was assessed by examining the phosphorylation level of the …

The Expression Of Mtor And Trib3 In Oligodendrocyte Lineage Cells, Katie Lazur

Senior Theses and Projects

Oligodendrocytes are a type of glial cell in the central nervous system that are responsible for producing the myelin sheath which allows for faster neuronal firing rates. Myelin production is a metabolically expensive process, which requires the oligodendrocytes to be aware of the nutrients are available to them. It has been demonstrated that the mammalian target of Rapamycin (mTOR) is required for the later stages of maturation in oligodendrocytes. However, when mTOR is inhibited by Rapamycin in the early stages of oligodendrocyte development, the oligodendrocytes are still able to fully differentiate. Tribbles Homolog 3 (Trib3) is a pseudo …

B Cells Migrate Into Remote Brain Areas And Support Neurogenesis And Functional Recovery After Focal Stroke In Mice, Sterling B. Ortega, Vanessa O. Torres, Sarah E. Latchney, Cody W. Whoolery, Ibrahim Z. Noorbhai, Katie Poinsatte, Uma M. Selvaraj, Monica A. Benson, Anouk J. M. Meeuwissen, Erik J. Plautz, Xiangmei Kong, Denise M. Ramirez, Apoorva D. Ajay, Julian P. Meeks, Mark P. Goldberg, Nancy L. Monson, Amelia J. Eisch, Ann M. Stowe

Neurology Faculty Publications

Lymphocytes infiltrate the stroke core and penumbra and often exacerbate cellular injury. B cells, however, are lymphocytes that do not contribute to acute pathology but can support recovery. B cell adoptive transfer to mice reduced infarct volumes 3 and 7 d after transient middle cerebral artery occlusion (tMCAo), independent of changing immune populations in recipient mice. Testing a direct neurotrophic effect, B cells cocultured with mixed cortical cells protected neurons and maintained dendritic arborization after oxygen-glucose deprivation. Whole-brain volumetric serial two-photon tomography (STPT) and a custom-developed image analysis pipeline visualized and quantified poststroke B cell diapedesis throughout the brain, including …

Mushroom Body-Specific Gene Regulation By The Swi/Snf Chromatin Remodeling Complex, Kevin Cj Nixon

Electronic Thesis and Dissertation Repository

Over the lifetime of an organism, neurons must establish, remodel, and maintain precise connections in order to form neural circuits that are required for proper nervous system functioning. Disruptions in these processes can lead to neurodevelopmental disorders such as intellectual disability (ID) and autism spectrum disorder. Mutations in genes encoding subunits of the SWI/SNF chromatin remodeling complex have been implicated in ID, yet the role of this complex in neurons is poorly understood. In this project, I established cell-type specific methods to examine the effect of SWI/SNF subunit knockdowns on gene transcription and chromatin structure in the memory-forming neurons of …

De-Coding The Impact Of Evolved Changes In Gene Expression And Cellular Phenotype On Primate Evolution, Trisha Zintel

Doctoral Dissertations

The goal of the dissertation work outlined here was to investigate the influence of proximal processes contributing to evolutionary differences in phenotypes among primate species. There are numerous previous comparative analyses of gene expression between primate brain regions. However, primate brain tissue samples are relatively rare, and my results have contributed to the pre-existing data on more well-studied primates (i.e. humans, chimpanzees, macaques, marmosets) as well as produced information on more rarely-studied primates (i.e. patas monkey, siamang, spider monkey). Additionally, the primary visual cortex has not previously been as extensively studied at the level of gene expression as other brain …

A Neural Mechanism For Capnotaxis In The Naked Mole-Rat, Michael Zions

Dissertations, Theses, and Capstone Projects

A Neural Mechanism for Capnotaxis in the Naked Mole-Rat

The Naked Mole-Rat (NM-R) is a small hairless rodent that has thrived underground in the Horn of Africa for the past 40 million years. It was first discovered in 1847, but has only been maintained in captivity and studied as a laboratory animal over the past 40 years. To date, more than 400 scientific papers have been published on this species. This is relatively few compared to established lab animals like rats and mice, but those papers contain a trove of information that has changed our understanding of the constraints of …

The Potential Of Bone Morphogenetic Protein 2 As A Neurotrophic Factor For Parkinson's Disease, Susan R. Goulding, Aideen M. Sullivan, Gerard W. O'Keeffe, Louise M. Collins

Department of Biological Sciences Publications

Parkinson's disease is the second most common neurodegenerative disorder; it affects 1% of the population over the age of 65. The number of people with Parkinson's disease is set to rapidly increase due to changing demographics and there is an unmet clinical need for disease-modifying therapies. The pathological hallmarks of Parkinson's disease are the progressive degeneration of dopaminergic neurons in the substantia nigra and their axons which project to the striatum, and the aggregation of α-synuclein; these result in a range of debilitating motor and non-motor symptoms. The application of neurotrophic factors to protect and potentially regenerate the remaining dopaminergic …

Characterizing The Diverse Cells That Associate With The Developing Commissures Of The Zebrafish Forebrain, Jake Schnabl, M.P.H Litz, Caitlin Schneider, N. Penkofflidbeck, Sarah Bashiruddin, M. S. Schwartz, Kristin Alligood, Michael Barresi

Zebrafish Forebrain Cellular Characterization

During embryonic development of bilateral organisms, neurons send axons across the midline at specific points to connect the two halves of the nervous system with a commissure. Little is known about the cells at the midline that facilitate this tightly regulated process. We exploit the con served process of vertebrate embryonic development in the zebrafish model system to elucidate the identity of cells at the midline that may facilitate postoptic (POC) and anterior commissure (AC) development. We have discovered that three differentgfap+ astroglial cell morphologies persist in contact with pathfinding axons throughout commissure formation. Similarly, olig2+ progenitor cells occupy delineated …