Laboratory and Basic Science Research Commons^™

In Silico Identification Of Small Molecule Agonist Binding Sites On Kcc2, Kenyon Mitchell, Alfred Amendolara, Ruth Hunter, Jaden Miner, Andrew Payne

Annual Research Symposium

Purpose: Potassium-Chloride Cotransporter 2 (KCC2) is a neuronal membrane protein specific to the central nervous system. It is responsible for removing Cl- ions from the intracellular space, maintaining a normal Cl- gradient essential for proper function at inhibitory synapses. Dysregulation causes an upward shift in the Cl- reversal potential resulting in a hyperexcitable state of the postsynaptic neuron. Existing literature indicates that KCC2 may be involved in the addiction pathway of a variety of drugs of abuse, including opioids and alcohol. This makes KCC2 an attractive potential drug target when treating substance use disorders. A novel direct KCC2 agonist, VU0500469, …

Associations Between Early Childhood Sleep, Memory Function, And Brain Development Across The Nap Transition, Sanna Lokhandwala

Doctoral Dissertations

Preschool-age children often distribute their sleep across a midday nap and overnight sleep. Skipping the nap is suggested to increase the duration and depth of deep sleep (i.e., slow wave activity; SWA). Moreover, missing the midday nap has been shown to impair learning processes. This may be because children’s brains at this point in development are immature, necessitating the intervening nap period to strengthen memories before they are forgotten. Nonetheless, at some point during the preschool years, many children begin transitioning naturally out of napping. It is unclear whether the memory benefits of overnight SWA after a skipped nap depend …

Exploring The Developmental Effects Of Antidepressants In Caenorhabditis Elegans, Alexandra Van Stone

Annual Research Symposium

It is so important to explore the potential side effects of antidepressants especially if these side effects could lead to a future detriment to an individual’s financial and social well-being. A better understanding of these side effects in regards to human developmental issues is imperative considering issues related to mental health and depression affect a large percentage of the population. In this study, we tested if Caenorhabditis (C.) elegans could be a potential model organism to predict possible side effects associated with select antidepressants. Their developmental problems potentially encountered upon drug treatment may be encountered in humans.

Methamphetamine-Induced Dna Double-Stranded Breaks: The Impact Of The Dopamine Transporter And Insights Into The Mechanisms Of Dna Damage In Mouse Neuro 2a Cells, Lizette Couto

Dissertations, Theses, and Capstone Projects

Methamphetamine (METH) abuse remains a global health concern, with emerging evidence highlighting its genotoxic potential. In the central nervous system METH enters dopaminergic cells primarily through the dopamine transporter (DAT), which controls the dynamics of dopamine (DA) neurotransmission by driving the reuptake of extracellular DA into the presynaptic neuronal cell. Additional effects of METH on the storage of DA in synaptic vesicles lead to the dysregulated cytosolic accumulation of DA. Previous studies have shown that after METH disrupts intracellular vesicular stores of DA, the excess DA in the cytosol is rapidly oxidized. This generates an abundance of reactive oxygen species …

Utilizing Crispr Cas9 To Visualize Dopamine Receptors In Caenorhabditis Elegans, Lauren Michelle Velasquez

Electronic Theses, Projects, and Dissertations

Dopamine (DA) is a neurotransmitter with imperative implications in many functions including movement, reward, and cognition. Studying the pathways of dopaminergic neurons at multiple levels allows us to understand the ways in which these systems can go wrong. We study dopamine in a model system such as the worm Caenorhabditis elegans because of its relatively simple and well-characterized nervous system. DA is involved in regulating chemosensory behaviors in worms. The purpose of this research project is to definitively answer the following question: Are the dopamine receptors DOP-1 and DOP-4 expressed in chemosensory neurons? Previous reporter assays show that neither of …

Effects Of Sex And Estrous Cycle On Intravenous Oxycodone Self-Administration And The Reinstatement Of Oxycodone-Seeking Behavior In Rats, Nicole M. Hinds, Ireneusz D. Wojtas, Corinne A. Gallagher, Claire M. Corbett, Daniel F. Manvich

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

The increasing misuse of both prescription and illicit opioids has culminated in a national healthcare crisis in the United States. Oxycodone is among the most widely prescribed and misused opioid pain relievers and has been associated with a high risk for transition to compulsive opioid use. Here, we sought to examine potential sex differences and estrous cycle-dependent effects on the reinforcing efficacy of oxycodone, as well as on stress-induced or cue-induced oxycodone-seeking behavior, using intravenous (IV) oxycodone self-administration and reinstatement procedures. In experiment 1, adult male and female Long-Evans rats were trained to self-administer 0.03 mg/kg/inf oxycodone according to a …

Role Of Chronic Stress-Induced Neuroinflammation In Rodent Locus Coeruleus Physiology And Anxiety-Like Behaviors, Arthur Anthony Alfonso Reyes

Graduate School of Biomedical Sciences Theses and Dissertations

The locus coeruleus (LC), the primary site of brain norepinephrine (NE), is a key anatomical brain region implicated in the stress response. Stress is a neuroendocrine physiologic response to a stressor that promotes organism survival through adaptive change and restoration of homeostasis. The central stress response, which drives behavioral and physiological change, is primarily mediated by activating the hypothalamic-pituitary-adrenal (HPA) axis. While advantageous in the short term, chronic stress exposure can lead to HPA axis and LC dysregulation, which are thought to contribute to the etiology of anxiety disorders. Previous studies demonstrate the effects of acute stress in increasing LC …

Swallowing Disrupts Tongue-Jaw Coordination During Chewing In A Rat Model Of Parkinson's Disease, Meejan Palhang, N. Charles, Francois Gould

Rowan-Virtua Research Day

The primary motor symptoms of Parkinson’s disease, including bradykinesia, rigidity, and tremor, are associated with difficulties regulating transitions between motor behaviors due to basal ganglia dysfunction. Chewing and swallowing, which are disordered in most patients with Parkinson’s disease, are two complex motor behaviors which overlap in time and share some neuromuscular components. The objective of this study is to identify how Parkinson’s disease affects the coordination of chewing and swallowing. We hypothesize that as a result of impaired regulation of shift between motor patterns, chewing cycles that occur with a swallow will be more affected that chewing cycles occurring in …

Extravasated Brain-Reactive Autoantibodies Perturb Neuronal Surface Protein Expression In Alzheimer's Pathology, Wardah Bajwa, Mary Kosciuk, Randel L. Swanson, Anuradha Krishnan, Venkat Venkataraman, Robert Nagele, Nimish Acharya

Rowan-Virtua Research Day

Background: Increased blood-brain barrier (BBB) permeability is reported in both the neuropathological and in vivo studies in both Alzheimer’s Disease (AD) and age matched cognitively normal, no cognitive impairment (NCI), subjects. Impaired BBB allows various vascular components such as immunoglobulin G (IgG) to extravasate into the brain and specifically bind to various neuronal surface proteins (NSP), also known as brain reactive autoantibodies (BrABs). This interaction is predicted to further enhance deposition of amyloid plaques.

Hypothesis: Interaction between extravasated BrABs and its cognate NSPs lower the expression of that NSPs in AD patients.

Methods: We selected Western blotting technique to study …

Mglu5 Inhibition In The Basolateral Amygdala Prevents Estrous Cycle-Dependent Changes In Cue-Induced Cocaine Seeking, Claire M. Corbett, Emily N. D. Miller, Jessica A. Loweth

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Drug associated cues are a common relapse trigger for individuals recovering from cocaine use disorder. Sex and ovarian hormones influence patterns of cocaine use and relapse vulnerability, with studies indicating that females show increased cue-induced craving and relapse vulnerability compared to males. In a rodent model of cocaine craving and relapse vulnerability, cue-induced cocaine seeking behavior following weeks of withdrawal from extended-access cocaine self-administration is higher in females in the estrus stage of the reproductive (estrous) cycle (Estrus Females) compared to both Males and females in all other stages (Non-Estrus Females). However, the neuronal substrates and cellular mechanisms underlying these …

Artificial Light At Night Disrupts Pain Behavior And Cerebrovascular Structure In Mice, Jacob Raymond Bumgarner

Graduate Theses, Dissertations, and Problem Reports

Artificial Light at Night Disrupts Pain Behavior and Cerebrovascular Structure in Mice

Jacob R. Bumgarner

Circadian rhythms are intrinsic biological processes that fluctuate in function with a period of approximately 24 hours. These rhythms are precisely synchronized to the 24- hour day of the Earth by external rhythmic signaling cues. Solar light-dark cycles are the most potent environmental signaling cue for terrestrial organisms to align internal rhythms with the external day. Proper alignment and synchrony of internal circadian rhythms with external environmental rhythms are essential for health and optimal biological function.

The modern human environment on Earth is no longer …

Norepinephrine Regulation Of Spatial Memory Using The Barnes Maze In Male And Female Rats, Serena Simpson, Ali Gheidi Phd, Nareen Sadik, Cameron J. Davidson Phd, Shane A. Perrine Phd

Medical Student Research Symposium

The role of norepinephrine (NE) in learning and memory has been extensively studied, yet its contribution remains to be clarified. This study aimed to investigate the role of NE on spatial learning and memory in female and male rats using a Barnes maze assay. We used N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4), a specific noradrenergic neurotoxin that can cross the blood brain barrier, to deplete NE stores. We hypothesized that brain NE ablation would attenuate spatial learning and memory in rats. Loss of NE by DSP-4 was determined by measuring NE (and dopamine and serotonin) levels in several brain regions using HPLC. For the …

Examining Levels Of Catecholamine Neurotransmitter Regulatory Proteins Within The Prefrontal Cortex Of Rodents Following Traumatic Brain Injury, Eleni Papadopoulos, Christopher P. Knapp, Claire M. Corbett, Jessica Loweth, Rachel L. Navarra

Rowan-Virtua Research Day

Traumatic brain injury (TBI) resulting from impact to the head can cause long lasting impairments of cognitive processes that lead to increased risk-taking behavior in clinical populations. Our laboratory has recently shown that female, but not age-matched male, rats increase preference for risky choices after multiple experimentally-induced mild TBI’s. Our overarching goal is to understand the neural mechanisms underlying TBI-induced increases in risk-taking behavior.

The prefrontal cortex (PFC) plays a prominent role in risk-based decision making. Sub[1]regions of the PFC include the medial PFC (mPFC), the orbitofrontal cortex (OFC), and the anterior cingulate cortex (ACC), and these sub[1]regions play specific …

Understanding Exosomal Extracellular Vesicles And Morphine In The Neuropathology Of Human Immunodeficiency Virus And Differential Zika Virus Strain-Associated Pathology, Allen Caobi

FIU Electronic Theses and Dissertations

Exosomal Extracellular Vesicles (xEVs), integral to intercellular communication and regulation of immune responses, have functional effects based on their contents, which they transport to neighboring cells. However, in the context of infection, EV cargo can be modulated, by either infected or uninfected cells. We hypothesize that CNS-associated neuropathology, is partially, due to the cargo transported by the exosomes. We theorize that the cargo released from infected cell-derived xEVs may either facilitate or inhibit viral neuropathogenicity. Here we investigated xEVs in the case of two neurotropic viruses, Zika virus (ZIKV) and Human Immunodeficiency Virus (HIV). The hallmark characteristic of ZIKV-infection is …

Investigating The Role Of The Basolateral Amygdala Plays In The Incubation Of Cue-Induced Cocaine Seeking Behavior, Claire Marie Corbett

Graduate School of Biomedical Sciences Theses and Dissertations

Cocaine use disorder is a chronic, relapsing brain disease. Sex and ovarian hormones are known to influence cocaine addiction liability and relapse vulnerability. However, little is known regarding the cellular and synaptic mechanisms contributing to sex differences in relapse vulnerability, including how these measures are influenced by hormonal fluctuations. To investigate sex differences in relapse vulnerability we use a rodent model of cocaine craving and relapse called the incubation model in which cue-induced seeking progressively increases or “incubates” during the first month of withdrawal from extended-access cocaine self-administration. Using this model, we have recently shown that females in the estrus …

Trkb Activity Alters Voluntary Alcohol Consumption In Nondependent Mice, Alfred Amendolara

Annual Research Symposium

No abstract provided.

Novel Methodology For The Investigation Of Dmrt3a Interneurons In Larval Zebrafish, Alfred Amendolara

Annual Research Symposium

No abstract provided.

Investigating The Effects Of In-Vivo Therapeutics Hypoxia Treatment Paradigms In Neurite Outgrowth Patterns, Jae Hyun Yoo

Theses and Dissertations--Medical Sciences

Spinal cord injury, specifically in the cervical C3-C4 region of the cervical spine, contributes to impaired breathing and a diminished quality of life. Therefore it is important to find effective and safe therapeutics to restore breathing function. Indeed, there are a myriad of research being performed in addition to valuable collaboration amongst different institutions. As such, inspired by a previous experiment, we decided to test our hypothesis that an enriching environment consisting of different hypoxic environments - sustained and intermittent hypoxia alongside normoxia - would result in neurite outgrowth. Moreover, we hypothesized that sustained hypoxia would result in the greatest …

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 …

Motor Unit Firing Rate Control Of Agonist Skeletal Muscle During Voluntary Isometric And Shortening Contractions With Limb Movement, Eric A. Kirk

Electronic Thesis and Dissertation Repository

Voluntary movements throughout mammalian lifespan require skeletal muscle contractions that are controlled by time- and recruitment-dependent firing rate patterns. Single motor unit (MU) activity reflects the final efferent neural drive to the muscle, yet the underlying neural control of movement at the MU level is not well understood. Using intramuscular electromyography single MU recordings, relationships between voluntary contraction kinematics and MU firing rates were evaluated in vivo, in groups of young and older adult participants.

The purpose of study one was to characterize how MU firing rates are differently scaled among muscles relative to voluntary contraction intensity. Across 12 …

Effect Of Carbon Monoxide Releasing Molecule 3 (Corm - 3) On Platelet Adhesion To Human Brain Microvascular Endothelial Cells, Najat S. El-Farra

Undergraduate Student Research Internships Conference

Sepsis is characterized by the widespread inflammation of the body. Systemic inflammation activates and recruits inflammatory cells (e.g., leukocytes) and platelets to the affected organs.

During these inflammatory conditions, human brain microvascular endothelial cells (hBMEC) and platelets both upregulate adhesive molecules rendering platelets to adhere to hBMEC.

Although carbon monoxide is thought of as a toxic molecule to many, previous work shows its anti-inflammatory properties. Evidence has shown carbon monoxide-releasing molecules (e.g., CORM-3; that release small, non-toxic amounts of CO) can combat the effects of severe inflammation in several in vivo animal model.

In this current study, we are looking …

Neuroactivational And Behavioral Correlates Of Psychosocial Stress-Induced Cocaine Seeking In Rats, Nicole M. Hinds, Ireneusz D. Wojtas, Desta M. Pulley, Stephany J. Mcdonald, Samantha De Guzman, Nicole E. Hubbard, Colin M. Kulick-Soper, Jessica J. Debski, Bianca Patel, Daniel Manvich

Rowan-Virtua Research Day

A prominent feature of cocaine abuse is a high risk of relapse even despite prolonged periods of abstinence. Psychosocial stress is thought to be a major contributor to the onset of cocaine craving and relapse in human substance abusers, yet most preclinical models of stress-induced relapse employ physical stressors (e.g., unpredictable footshock) or pharmacological stressors (e.g., yohimbine to elicit a drug seeking response) and do not rely upon psychosocial stress per se. Importantly, social stressors are well known to activate distinct neural circuits within the brain as compared to other stressors. It is therefore possible that currently available animal models …

Corticospinal Excitability During A Perspective Taking Task As Measured By Tms-Induced Motor Evoked Potentials, Elizabeth Murray, Janet Brenya, Katherine Chavarria, Karen J. Kelly, Anjel Fierst, Nathira Ahmad, Caroline Anton, Layla Shaffer, Kairavi Kapila, Logan Driever, Kayla Weaver, Caroline Dial, Maya Crawford, Iso Hartman, Tommy Infantino, Fiona Butler, Abigail Straus, Shakeera L. Walker, Brianna Balugas, Matthew Pardillo, Briana Goncalves, Julian Keenan

Department of Biology Faculty Scholarship and Creative Works

Only by understanding the ability to take a third-person perspective can we begin to elucidate the neural processes responsible for one’s inimitable conscious experience. The current study examined differences in hemispheric laterality during a first-person perspective (1PP) and third-person perspective (3PP) taking task, using transcranial magnetic stimulation (TMS). Participants were asked to take either the 1PP or 3PP when identifying the number of spheres in a virtual scene. During this task, single-pulse TMS was delivered to the motor cortex of both the left and right hemispheres of 10 healthy volunteers. Measures of TMS-induced motor-evoked potentials (MEPs) of the contralateral abductor …

Long-Term Impacts Of Acute Stressor Exposure On Locus Coeruleus Function And Anxiety-Like Behavior In Rats, Olga Borodovitsyna

Graduate School of Biomedical Sciences Theses and Dissertations

Stress is a physiological state characterized by behavioral arousal that occurs during exposure to harmful or threatening stimuli, and usually facilitates an adaptive behavioral response. The persistence of stress sometimes causes it to become maladaptive, potentially contributing to disease development, including physiological complications with altered neuroendocrine signaling and impaired function of organ systems, and psychological conditions including depression and anxiety. Anxiety disorders in particular are associated with a history of stress and are the most common class of mental disorders, with a lifetime prevalence of 33.7% in the general population. The locus coeruleus (LC) is a major node in the …

Influence Of 2,5-Dimethoxy-4-Iodoamphetamine (Doi) On Ethanol Preference And Consumption In C57bl/6 Male Mice, Alaina M. Jaster, Sam Gottlieb, Michael Miles, Javier González-Maeso

Graduate Research Posters

Substance use disorders (SUD) account for a large number of mental health diagnosis in the United States and around the world. Approximately 13.6 million adults 26 or older and 5.1 million young adults (ages 18-24) battled with a SUD in 2017. Alcohol Use Disorder (AUD) alone effects nearly 6% of the adult population within the United States. This creates a substantial burden on the individual, with alcohol being the third-leading cause of preventable death in the United States. Few treatments for AUD exist, with no new FDA-approved therapeutic treatments within the last 15 years. Additionally, the limited treatments we do …

Developmental Influences On The Initial Subjective Rewarding Effects Of Etoh, Madison Waldron

Master’s Theses

The present studies were aimed to better understand developmental contributions to the risk for disordered drinking, and facilitate the long-term goal of developing effective interventions for individuals at high risk for alcohol use disorders. Experiment 1 assessed the effect of adolescent pre-exposure to ethanol on adult place preference, as well as, sex- and beta-endorphin(bE)-related contributions. Adolescent C57BL/6J and bE deficient mice were injected with 1.5g/kg of ethanol or saline and put back into their home cages. At the time of adulthood, we employed a single-exposure conditioned place preference paradigm (SE-CPP) to investigate the impact of preexposure on the initial subjective …

Estrogen Disruption Of Hypothalamic Neural Activity, Princess Dickson

Cal Poly Humboldt theses and projects

The brain is highly dependent on the endocrine system for proper neurodevelopment, as it plays a key role in many biological processes. Bisphenol A is a chemical found in plastics that has the potential to mimic the effects of Estrogen in the body, at least weakly. People interact with plastic that contains BPA regularly, and people are at risk for exposure even before being born. The abundance of BPA, along with other exogenous estrogens, makes examining the relationship between early exposure and changes in brain activity imperative. The current study aims to establish a relationship between disrupted estrogen function and …

Manipulating The Perineuronal Net In The Deep Cerebellar Nucleus, Deidre E. O'Dell

Graduate Theses, Dissertations, and Problem Reports

Perineuronal nets (PNN) are a type of specialized extracellular matrix in the central nervous system. The PNN forms during postnatal development but the ontogeny of the PNN has yet to be elucidated. Studying the PNN in the rat brain may allow us to further understand the PNN’s role in development, learning, and memory. The PNN is fully developed in the deep cerebellar nuclei (DCN) of rats by post-natal day 18. By using enzymatic digestion of the PNN with chondroitinase ABC (ChABC), we studied how digestion of the PNN affects cerebellar-dependent eyeblink conditioning (EBC) and performed electrophysiological recordings from DCN neurons. …

Mitochondrial Aspects Of Neuronal Pathology In Triple-Transgenic Alzheimer’S Disease Mice, John Zachary Cavendish

Graduate Theses, Dissertations, and Problem Reports

Alzheimer’s disease (AD) is a fatal, progressive neurodegenerative disease afflicting millions of people in the United States alone and is the only one of the top leading causes of morbidity and mortality with no effective disease-modifying therapies. It is the most common form of dementia, affecting one in three people over the age of 85. While the hallmarks of the disease include accumulation of beta-amyloid-based extracellular plaques and hyperphosphorylated tau-based intracellular neurofibrillary tangles, treatment strategies centered on removing or mitigating these components of AD have all failed in humans. Mitochondrial dysfunction has been increasingly recognized as an early and consistent …

Rapid Golgi Stain For Dendritic Spine Visualization In Hippocampus And Prefrontal Cortex, Maya Frankfurt, Rachel E. Bowman

Psychology Faculty Publications

Golgi impregnation, using the Golgi staining kit with minor adaptations, is used to impregnate dendritic spines in the rat hippocampus and medial prefrontal cortex. This technique is a marked improvement over previous methods of Golgi impregnation because the premixed chemicals are safer to use, neurons are consistently well impregnated, there is far less background debris, and for a given region, there are extremely small deviations in spine density between experiments. Moreover, brains can be accumulated after a certain point and kept frozen until further processing. Using this method any brain region of interest can be studied. Once stained and cover …