Neuroscience and Neurobiology Commons^™

P2x2 Dominant Deafness Mutations Have No Negative Effect On Wild-Type Isoform: Implications For Functional Rescue And In Deafness Mechanism, Yan Zhu, Juline Beudez, Ning Yu, Thomas Grutter, Hong-Bo Zhao

Otolaryngology--Head & Neck Surgery Faculty Publications

The P2X2 receptor is an ATP-gated ion channel, assembled by three subunits. Recently, it has been found that heterozygous mutations of P2X2 V60L and G353R can cause autosomal dominant nonsyndromic hearing loss. However, the underlying mechanism remains unclear. The fact that heterozygous mutations cause deafness suggests that the mutations may have dominant-negative effect (DNE) on wild-type (WT) P2X2 isoforms and/or other partners leading to hearing loss. In this study, the effect of these dominant deafness P2X2 mutations on WT P2X2 was investigated. We found that sole transfection of both V60L and G353R deafness mutants could efficiently target to the plasma …

Neuronal Degeneration And Short-Term Memory Impairment After Tbi, Obiamaraije Igwe

Posters-at-the-Capitol

Traumatic brain injury (TBI) was associated with impaired short-term memory with causes of vehicle accidents and falls. Protein plaques containing fibrinogen (Fg), are associated with memory loss. After TBI, Fg in blood was higher than normal (>~2 mg/ml), which resulted in increased Fg in extravascular space. Therefore, Fg bonded to its endothelial receptor intercellular adhesion molecule-1 (ICAM-1). Fg then interacted with cellular prion protein (PrPC), which had a strong effect on the loss of memory and cognition. Mechanisms of Fg and PrPC complex formation and its functional implication are not known. This present study tested the level of Fg-PrPC …

Machine Learning Analysis Identifies Drosophila Grunge/Atrophin As An Important Learning And Memory Gene Required For Memory Retention And Social Learning, Balint Kacsoh

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Single-Base Resolution Mapping Of 5-Hydroxymethylcytosine Modifications In Hippocampus Of Alzheimer's Disease Subjects, Elizabeth M. Ellison, Melissa A. Bradley-Whitman, Mark A. Lovell

Chemistry Faculty Publications

Epigenetic modifications to cytosine have been shown to regulate transcription in cancer, embryonic development, and recently neurodegeneration. While cytosine methylation studies are now common in neurodegenerative research, hydroxymethylation studies are rare, particularly genome-wide mapping studies. As an initial study to analyze 5-hydroxymethylcytosine (5-hmC) in the Alzheimer’s disease (AD) genome, reduced representation hydroxymethylation profiling (RRHP) was used to analyze more than 2 million sites of possible modification in hippocampal DNA of sporadic AD and normal control subjects. Genes with differentially hydroxymethylated regions were filtered based on previously published microarray data for altered gene expression in hippocampal DNA of AD subjects. Our …

Pharmacological Antagonism And The Olfactory Code, Mihwa Na

Dissertations, Theses, and Capstone Projects

Mammals can detect and discriminate uncountable odors through their odorant receptors. To accommodate the countless and diverse odors, exceptionally large numbers of odorant receptor (OR) genes are expressed in mammals. In addition, the mammals utilize a combinatorial code, where an odorant molecule can activate multiple ORs; an OR also responds to a set of multiple odorants. In nature, an odor is often a complex mixture of multiple odorant molecules. The combination of the ORs activated by each constituent generates the unique olfactory code for the particular odor.

Some odorants can antagonize select ORs, as discussed in Chapter 1. An antagonist …

Regulation Of The Amyloid Precursor Protein By Prostaglandin J2, A Mediator Of Inflammation: Relevance To Alzheimer’S Disease, Teneka L. Jean-Louis

Dissertations, Theses, and Capstone Projects

Inflammation plays a major role in Alzheimer’s disease (AD). Investigating how specific mediators of inflammation contribute to neurodegeneration in AD is crucial. Our studies focused on cyclooxygenases, which are key enzymes in inflammation and highly relevant to AD. Cyclooxygenases (COX -1, constitutive; COX-2, inducible) have emerged as important determinants of AD pathogenesis and progression. COX-2 is highly induced in AD, correlating with AD severity, and COX-1 is also involved in AD. Cyclooxygenases are the rate-limiting enzymes that convert arachidonic acid into prostaglandins (PGs), the principal mediators of CNS neuroinflammation.

The overall GOAL of these studies was to address the mechanisms …

C. Elegans Avoids Toxin-Producing Streptomyces Using A Seven Transmembrane Domain Chemosensory Receptor, Alan Tran, Angelina Tang, Colleen O’Loughlin, Anthony Balistreri, Eric Chang, Doris Coto Villa, Joy Li, Aruna Varshney, Vanessa Jimenez, Jacqueline Pyle, Bryan Tsujimoto, Christopher Wellbrook, Christopher Vargas, Alex Duong, Nebat Ali, Sarah Matthews, Samantha Levinson, Sarah Woldemariam, Sami Khuri, Martina Bremer, Daryl Eggers, Noelle L’Etoile, Laura Miller Conrad, Miri Vanhoven

Faculty Publications, Chemistry

Predators and prey co-evolve, each maximizing their own fitness, but the effects of predator–prey interactions on cellular and molecular machinery are poorly understood. Here, we study this process using the predator Caenorhabditis elegans and the bacterial prey Streptomyces, which have evolved a powerful defense: the production of nematicides. We demonstrate that upon exposure to Streptomyces at their head or tail, nematodes display an escape response that is mediated by bacterially produced cues. Avoidance requires a predicted G-protein-coupled receptor, SRB-6, which is expressed in five types of amphid and phasmid chemosensory neurons. We establish that species of Streptomyces secrete dodecanoic acid, …

Thiamine Deficiency And Neurodegeneration: The Interplay Among Oxidative Stress, Endoplasmic Reticulum Stress, And Autophagy, Dexiang Liu, Zunji Ke, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Thiamine (vitamin B1) is an essential nutrient and indispensable for normal growth and development of the organism due to its multilateral participation in key biochemical and physiological processes. Humans must obtain thiamine from their diet since it is synthesized only in bacteria, fungi, and plants. Thiamine deficiency (TD) can result from inadequate intake, increased requirement, excessive deletion, and chronic alcohol consumption. TD affects multiple organ systems, including the cardiovascular, muscular, gastrointestinal, and central and peripheral nervous systems. In the brain, TD causes a cascade of events including mild impairment of oxidative metabolism, neuroinflammation, and neurodegeneration, which are commonly observed in …

Modulation Of The Sodium/Potassium Atpase Function And Expression By Transcranial Direct Current Stimulation Of The Right Sensorimotor Cortex In Mice, Salim Bendaoud

Dissertations, Theses, and Capstone Projects

Direct current stimulation is used as a noninvasive therapeutic technique to enhance motor recovery following stroke, and to improve cognitive functions. This technique also showed promising results in the treatment of depression, schizophrenia, and multiple sclerosis. Transcranial direct current stimulation has been proven to cause a polarization (depolarization or hyperpolarization) of the target tissues depending on the polarity of the current and cell orientation. Because of the induced polarization, the spontaneous activity of the neurons is further affected. With exception to this electrophysiological effect, the overall biological mechanisms of transcranial direct current stimulation on the underlying tissues remain largely unknown. …

Distribution And Activation Of Catecholaminergic Neurons In The Brain Of Male Plainfin Midshipman Fish: Divergence In Behavior And Reproductive Phenotype, Zachary Ghahramani

Dissertations, Theses, and Capstone Projects

The plainfin midshipman fish, Porichthys notatus, provides an excellent opportunity for delimiting the influence of neurochemical content on vertebrate vocal behavior, in part because the production and recognition of social-acoustic signals is vital to their reproductive behavior. There are two distinct reproductive male morphs that follow divergent developmental trajectories with corresponding alternative reproductive tactics: type I males are the territorial/nesting morph that vocally court females during the summer breeding season while type II males do not court females, but instead sneak spawn in competition with type I males. Catecholaminergic neurons, which synthesize and release the neurotransmitters dopamine or noradrenaline, …

Modulation Of Spasticity By Trans-Spinal Direct Current Stimulation In Animals With Spinal Cord Injury, Wagdy Mekhael

Dissertations, Theses, and Capstone Projects

Central nervous system injuries usually produce motor impairments that are exacerbated by pathologically altered muscle tone. Abnormal muscle tone interferes with voluntary movement and is associated with loss of dexterity. Prior work in our laboratory demonstrated that 30-second trans-spinal direct current (DC) stimulation can temporarily modify muscle tone in anesthetized spastic mice after spinal cord injury (SCI). These experiments described DC-induced muscle tone responses to be polarity-dependent. That is, anodal stimulation (current passed from the lumbar spine to sciatic nerve) decreased muscle tone, and cathodal stimulation (current passed from the sciatic nerve to the lumbar spine) increased it. The present …

Study Of Regulated Cell Death In Two Systems: Pd-1 In Natural Killer Cells And Rip3 In Neurons, Yu Huang

Dissertations and Theses (Open Access)

Cell death is not only an essential phenomenon in normal development and homeostasis, but also crucial in various pathologies. It is now clear that many types of cell death can be regulated by pharmacological or genetic interventions. These were largely achieved by identifying the molecular mechanisms underlying the regulated cell death (RCD). While in the immune system, RCD needs to be facilitated to help the clearance of pathogens and tumors, in healthy cells, especially the terminally differentiated neurons in the nervous system, it is more desirable to protect cells from dying due to stress under pathological conditions. Thus, understating the …

Pattern Recognition Receptors, Immune Proteins, And Nf-Κb Signaling Regulate Behaviors Associated With Aging Phenotypes, Nicholas W. Dekorver

Theses & Dissertations

The aging process is accompanied by functional impairments, including reduced locomotor function, fragmentation of active states, and alterations in energy balance. Our lab has demonstrated that immune proteins are increased in specific regions of the mouse brain that correlate with strain specific deficits. These immune proteins include toll-like receptors (Tlr), class I major histocompatibility complex proteins (MHC I), and complement proteins. There is an increasing appreciation for the role of immune proteins in neurodevelopment; however, their involvement in age-associated deficits is poorly understood. Here, we present data demonstrating that 1) activation of a specific immune receptor (Tlr2) leads to changes …

Inflammasome Activation By Methamphetamine Potentiates Lipopolysaccharide Stimulation Of Il-1Β Production In Microglia, Enquan Xu

Theses & Dissertations

Methamphetamine (Meth) is a psychostimulant drug that is widely abused all around the world. The administration of Meth causes a strong instant euphoria effect, and long-term of abuse is correlative of drug-dependence and neurotoxicity. The neuroimaging studies demonstrated that the long-term abuse of Meth is associated with the reduction of the dopamine transporter (DAT) and vesicular monoamine transporter (VMAT2) in the striatum. Neuroinflammation is well-accepted as an important mechanism underlying the Meth-induced neurotoxicity. The over-activated microglia were found both in Meth human abusers and animal models.

NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome is the most predominant Nod-like …

Chaperoning Ef Hands That Shape Calcium Response: Ncald, Hpca And S100b, Jingyi Zhang

Graduate School of Biomedical Sciences Theses and Dissertations

All organisms have an internal clock with a defined period between repetitions of activities. The period for circadian clock in human is 24.5 hours, while in mouse and rat, it is 23.5 hours. However, all organisms are forced to be in synchronization with their environment. A major environmental force that resets the internal clock to 24 hours is light. This phenomenon is defined as “light entrainment” or “phase-setting”. It is unclear how this entrainment process occurs. Studies from this laboratory indicate a role for two neuronal calcium sensor proteins: Neurocalcin  (NCALD) and S100B. For these two genes, mRNA as …

Evolution Of Caffeine Biosynthetic Enzymes And Pathways In Flowering Plants, Ruiqi Huang

Dissertations

Convergent evolution generally refers to the independent evolution of similar biological function more than once in unrelated species. Caffeine is thought to have evolved by convergence, and is naturally produced through secondary metabolism in plants to defend against pathogen attack and insect feeding or to attract pollinators. The same caffeine biosynthetic pathway has been elucidated in Camellia (tea) and Coffea (coffee), in which xanthosine is sequentially methylated to caffeine via 7-methylxanthine and theobromine. However, although the same catalysis pathway is used, different (paralogous) enzymes in the SAMT/BAMT/theobromine synthase (SABATH) multigene family are used in the two species. In my dissertation, …

Modification Of Aplysia Feeding Network By L-Dopa And Dopamine-Dependent Learning, Curtis Neveu, Curtis L. Neveu

Dissertations and Theses (Open Access)

Dopamine (DA) is a ubiquitous neuromodulator of neuronal networks in the animal kingdom and has a well-established role in modulating motor behavior and encoding reward information. Although the effects of DA and DA-dependent learning at the behavioral and molecular levels are well-understood, many questions still remain concerning the effects of DA at the network level. DA-dependent learning effects on a neuronal circuit were examined by measuring the biophysical properties before and after in vitro operant conditioning (OC) of the feeding circuit of Aplysia. OC reduced the excitability of B4 and the B4-to-B51 synaptic connection, with a trend towards an …

Elucidating Mechanisms Of Protein Aggregation In Alzheimer’S Disease Using Antibody-Based Strategies., Benjamin A. Colvin

Dissertations

Alzheimer’s Disease (AD) is a devastating neurodegenerative disorder. There are two characteristic histopathological hallmarks in the brain: senile plaques and neurofibrillary tangles, composed of insoluble aggregates of the amyloids Amyloid-β (Aβ) and tau protein, respectively. These diagnostic markers, though distinctive, are not apparent effectors of AD pathology. Evidence has mounted suggesting smaller soluble aggregates (oligomers) of Aβ or tau are the true drivers of disease progression. This dissertation presents several amyloid biophysics projects. Aggregate biophysical parameters such as weight, shape, and conformation were measured using a range of methodologies, including Multiangle Light Scattering, Dynamic Light Scattering, UV-Circular Dichroism, UV-Fluorescence, Scanning …

Drug-Resistant Epilepsy: Multiple Hypotheses, Few Answers, Fei Tang, Anika M. S. Hartz, Björn Bauer

Pharmaceutical Sciences Faculty Publications

Epilepsy is a common neurological disorder that affects over 70 million people worldwide. Despite the recent introduction of new antiseizure drugs (ASDs), about one-third of patients with epilepsy have seizures refractory to pharmacotherapy. Early identification of patients who will become refractory to ASDs could help direct such patients to appropriate non-pharmacological treatment, but the complexity in the temporal patterns of epilepsy could make such identification difficult. The target hypothesis and transporter hypothesis are the most cited theories trying to explain refractory epilepsy, but neither theory alone fully explains the neurobiological basis of pharmacoresistance. This review summarizes evidence for and against …

Osteopontin Facilitates West Nile Virus Neuroinvasion Via Neutrophil “Trojan Horse” Transport, Amber M. Paul, Dhiraj Acharya, Laurel Duty, E. Ashley Thompson, Linda Le, Dobrivoje S. Stokic, A. Arturo Leis, Fengwei Bai

Publications

West Nile virus (WNV) can cause severe human neurological diseases including encephalitis and meningitis. The mechanisms by which WNV enters the central nervous system (CNS) and host factors that are involved in WNV neuroinvasion are not completely understood. The proinflammatory chemokine osteopontin (OPN) is induced in multiple neuroinflammatory diseases and is responsible for leukocyte recruitment to sites of its expression. In this study, we found that WNV infection induced OPN expression in both human and mouse cells. Interestingly, WNV-infected OPN deficient (Opn−/−) mice exhibited a higher survival rate (70%) than wild type (WT) control mice (30%), suggesting OPN plays a …

Neuroanatomical Tracing Of The Gut -- Brain Axis, Ricardo P. Torres, Elizabeth A. Davis, Coltan G. Parker, Megan J. Dailey

PRECS student projects

This poster summarizes a variety of methods to further characterize the gut-brain axis by tracing motor and sensory nerves between the gut and brain and identifying cell bodies in the sensory ganglia. Determines the meth method to trace the sensory and motor nerves was through fluorescence and the best method to identify sensory neuron cell bodies was the Nissi stain.

Allosteric Modulatory Effects Of Sri-20041 And Sri-30827 On Cocaine And Hiv-1 Tat Protein Binding To Human Dopamine Transporter, Wei-Lun Sun, Pamela M. Quizon, Yaxia Yuan, Wei Zhang, Subramaniam Ananthan, Chang-Guo Zhan, Jun Zhu

Molecular Modeling and Biopharmaceutical Center Faculty Publications

Dopamine transporter (DAT) is the target of cocaine and HIV-1 transactivator of transcription (Tat) protein. Identifying allosteric modulatory molecules with potential attenuation of cocaine and Tat binding to DAT are of great scientific and clinical interest. We demonstrated that tyrosine 470 and 88 act as functional recognition residues in human DAT (hDAT) for Tat-induced inhibition of DA transport and transporter conformational transitions. Here we investigated the allosteric modulatory effects of two allosteric ligands, SRI-20041 and SRI-30827 on cocaine binding on wild type (WT) hDAT, Y470 H and Y88 F mutants. Effect of SRI-30827 on Tat-induced inhibition of [³H]WIN35,428 …

Microarray Analysis Of Aging-Associated Immune System Alterations In The Rostral Ventrolateral Medulla Of F344 Rats, Sivasai Balivada, Chanran Ganta, Yongqing Zhang, Hitesh Pawar, Richard Ortiz, Kevin Becker, Arshad Khan, Michael Kenney

Selected Works Temporary Series

The rostral ventrolateral medulla (RVLM) is an area of the brain stem that contains diverse neural substrates that are involved in systems critical for physiological function. There is evidence that aging affects some neural substrates within the RVLM, although age-related changes in RVLM molecular mechanisms are not well established. The goal of the present study was to characterize the transcriptomic profile of the aging RVLM and to test the hypothesis that aging is associated with altered gene expression in the RVLM, with an emphasis on immune system associated gene transcripts. RVLM tissue punches from young, middle-aged, and aged F344 rats …

Microarray Analysis Of Aging-Associated Immune System Alterations In The Rostral Ventrolateral Medulla Of F344 Rats, Balivada, Chanran Ganta, Yongqing Zhang, Hitesh Pawar, Richard Ortiz, Kevin Becker, Arshad Khan, Michael Kenney

Departmental Papers (Biology)

The rostral ventrolateral medulla (RVLM) is an area of the brain stem that contains diverse neural substrates that are involved in systems critical for physiological function. There is evidence that aging affects some neural substrates within the RVLM, although age-related changes in RVLM molecular mechanisms are not well established. The goal of the present study was to characterize the transcriptomic profile of the aging RVLM and to test the hypothesis that aging is associated with altered gene expression in the RVLM, with an emphasis on immune system associated gene transcripts. RVLM tissue punches from young, middle-aged, and aged F344 rats …

Igf-1 Mediated Neurogenesis Involves A Novel Rit1/Akt/Sox2 Cascade, Sajad Mir, Weikang Cai, Shaun W. Carlson, Kathryn E. Saatman, Douglas A. Andres

Molecular and Cellular Biochemistry Faculty Publications

Insulin-like growth factor 1 (IGF-1) is known to have diverse effects on brain structure and function, including the promotion of stem cell proliferation and neurogenesis in the adult dentate gyrus. However, the intracellular pathways downstream of the IGF-1 receptor that contribute to these diverse physiological actions remain relatively uncharacterized. Here, we demonstrate that the Ras-related GTPase, RIT1, plays a critical role in IGF-1-dependent neurogenesis. Studies in hippocampal neuronal precursor cells (HNPCs) demonstrate that IGF-1 stimulates a RIT1-dependent increase in Sox2 levels, resulting in pro-neural gene expression and increased cellular proliferation. In this novel cascade, RIT1 stimulates Akt-dependent phosphorylation of …

Hypothesis Of K+-Recycling Defect Is Not A Primary Deafness Mechanism For Cx26 (Gjb2) Deficiency, Hong-Bo Zhao

Otolaryngology--Head & Neck Surgery Faculty Publications

K⁺-recycling defect is a long-standing hypothesis for deafness mechanism of Connexin26 (Cx26, GJB2) mutations, which cause the most common hereditary deafness and are responsible for >50% of nonsyndromic hearing loss. The hypothesis states that Cx26 deficiency may disrupt inner ear gap junctions and compromise sinking and recycling of expelled K⁺ ions after hair cell excitation, causing accumulation of K⁺-ions in the extracellular space around hair cells producing K⁺-toxicity, which eventually induces hair cell degeneration and hearing loss. However, this hypothesis has never been directly evidenced, even though it has been widely referred …

Rat Hind Limb Nociceptive Withdrawal Response To Heat And Mechanical Stimuli Depends On Initial Position Of The Paw But Not Stimulus Location, Giavanna Verdi

Senior Honors Projects, 2010-2019

Mammals rapidly withdraw their hind limb in response to noxious stimulation, which is a protective movement known as the nociceptive withdrawal response (NWR). The NWR has been previously studied in spinalized, decerebrated and anesthetized non-human and human mammals; however, there is minimal information on the NWR in intact, unanesthetized non-human mammals.

The first specific aim was to identify the factors that determine the direction and magnitude of the NWR in intact, unanesthetized rats. Based on previous studies, we hypothesized that the location of stimulation and the initial position of the paw preceding the NWR will influence the direction and magnitude …

Basal And Experience Dependent Ampar And Synapse Dynamics: Alterations In A Mouse Model Of Fragile X Syndrome, Anand Suresh

Theses & Dissertations

Dendritic spines are the principal sites of excitatory synapses in the neurons of mammalian central nervous system. Spine are plastic, undergoing structural and functional changes under basal and experience dependent conditions. Spine properties are altered in a number of neurodevelopmental disorders including the Fragile X syndrome (FXS) which is the most common inherited form of intellectual disability. The structural reorganization of dendritic spines is thought to be associated with synaptic plasticity mechanisms that are deficient in FXS. A number of synaptic plasticity mechanisms involve modulation of synaptic strength via insertion or removal of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR). However, the link …

Major Neurotransmitters In The Brain, Amy S. Yu '17

Independent Study

Arguably the most important and powerful organ in the human body, the brain controls virtually everything one does. From chewing gum to running a marathon, the brain dictates one’s physical responses and actions, while also mediating learning, memory, and emotions. These functions are all regulated by neurotransmitter activity in the brain. While the brain works in complex ways, recent discoveries about neurotransmitters allow us to better understand the underlying mechanisms of brain operation. Each neurotransmitter fulfills a distinct role, but they rely on one another to perform certain activities in the brain as well. The purpose of this review is …

A Behavioral Prerequisite For The Genetic Analysis Of Auditory Feature Detection Mechanisms In Female Crickets, Rebecca L. Blisko

Senior Honors Projects

Sexual dimorphism is exhibited across all cricket species and is a central aspect of the mating processes of these insects. Only male crickets possess wing structures and pattern generators in the central nervous system that allow them to produce a mating call that is unique to their species in order to attract conspecific females. Conspecific females possess an auditory feature detection circuit in the central nervous system that is capable of detecting the species-specific frequency and temporal pattern of sound pulses within a male call. In order for dimorphic differences in mating behavior to result in successful continuation of a …