Molecular and Cellular Neuroscience Commons^™

Novel Strategies For Glutamate Clearance In The Glia-Deprived Synaptic Hub Of C. Elegans, Joyce Chan

Dissertations, Theses, and Capstone Projects

As the major excitatory neurotransmitter in the mammalian brain, Glutamate (Glu) is critical for normal neuronal physiology. Disruption in Glu clearance results in hyper-stimulation of glutamatergic circuits, potentially leading to excitotoxic neurodegeneration. The canonical model of brain connectivity describes glutamatergic synapses as well insulated and enveloped by glia. These glia express Glu Transporters (GluTs) which work to clear Glu following synaptic activity. However, critical areas of the brain such as the mammalian hippocampus display poor synaptic isolation, which may result in Glu spillover between adjacent synapses and subsequent loss of circuit specificity. How accurate signal transmission is achieved in these …

Importin-Mediated Pathological Tau Nuclear Translocation Causes Disruption Of The Nuclear Lamina, Tdp-43 Mislocalization And Cell Death, Robert F. Candia, Leah S. Cohen, Viktoriya Morozova, Christopher Corbo, Alejandra D. Alonso

Publications and Research

Tau is a cytosolic protein that has also been observed in the nucleus, where it has multiple proposed functions that are regulated by phosphorylation. However, the mechanism underlying the nuclear import of tau is unclear, as is the contribution of nuclear tau to the pathology of tauopathies. We have previously generated a pathological form of tau, PH-tau (pseudophosphorylation mutants S199E, T212E, T231E, and S262E) that mimics AD pathological behavior in cells, Drosophila, and a mouse model. Here, we demonstrated that PH-tau translocates into the nucleus of transiently transfected HEK-293 cells, but wildtype tau does not. We identified a putative …

Investigation Of The Neuroprotective Effects Of Grape Seed Extract On Trigeminal Ganglion Primary Cultures, Sophia Rose Antonopoulos

Graduate Theses/Dissertations

Migraine and temporomandibular disorders (TMD) are prevalent, debilitating orofacial pain conditions involving peripheral and central sensitization of the trigeminal system. The pro-inflammatory neuropeptide calcitonin gene-related peptide (CGRP), which is synthesized and secreted from trigeminal ganglion neurons, is implicated in the underlying pathology of migraine and TMD. Secreted CGRP modulates the excitability state of neurons and glial cells that express CGRP receptors. Recent studies from our lab in preclinical models of migraine and TMD have provided evidence that dietary supplementation with a proanthocyanin-enriched grape seed extract (GSE) inhibits trigeminal pain signaling. The effect of GSE was blocked by an antagonist of …

Estrogen Modulation Of Vta Dopamine Neuron Physiology And Behavioral Responsivity To Variable Social Stressors, Mary R. Shanley

Dissertations, Theses, and Capstone Projects

The behavioral output of different animals, or even the same animal in different contexts, is remarkably variable in response to the same external stimulus. This behavioral diversity is due to the complex integration of external and internal stimuli, through both neuronal and hormonal signals that selects the best behavioral response. By their nature as long-distance signaling molecules, hormones play a critical role in communicating information about internal states across the organism. Many hormones produced in the periphery target the central nervous system to modulate animal behavior, selecting for behaviors that are appropriate over behaviors that are maladaptive in that specific …

Effects Of Palmitate On The Expression Of Inflammatory Cytokines In Microglial Cells, Shiyu Ma

Seton Hall University Dissertations and Theses (ETDs)

Obesity has become a pandemic health issue for the development of more serious illnesses such as insulin resistance, cardiovascular diseases, and hypertension. Among those pathological conditions, low grade chronic inflammation triggered by saturated fatty acids (SFA) such as palmitate (PA) has been suggested to be the culprit of crimes and various signaling modulators ranging from cellular surface receptors such as toll like receptors (TLRs) and G- protein – coupled receptor 40 (GPR40) to intracellular kinases like mitogen-activated protein kinase (MAPK) and protein kinase C (PKC) have been postulated. In this study, mouse BV2 cells were treated with different concentrations of …

Having A High-Activity Catechol-O-Methyltransferase Allele Is Associated With Elevated Anxiety And Lower Salivary Dehydroepiandrosterone But Also Lower Alpha Amylase In Children With Chromosome 22q11.2 Deletion Syndrome., Jessie Beebe

LSU New Orleans Theses and Dissertations

Chromosome 22q11.2 deletion syndrome (22q11.2DS) results from a hemizygous deletion located on the long arm of chromosome 22. The most common deletion sizes affect between 30 and 90 genes. Individuals with 22q11.2DS may develop serious developmental and psychiatric disorders. The phenotype is highly variable, however, and may be influenced by allelic variation of the retained copies of genes covered by the deletion. I set out to examine the effects of two genes, catechol-O-methyltransferase (COMT) and proline dehydrogenase (PRODH), in relation to anxiety in children and adolescents with 22q11.2DS. Individuals with the major COMT allele (higher activity) have significantly higher anxiety …

Exploring The Relationship Between Cellular Senescence, Apolipoprotein E, And Alzheimer’S Disease, Buay Deng

Natural Sciences and Mathematics | Biological Sciences Master's Theses

Alzheimer’s disease (AD) is the most common form of dementia in the world and currently affects more than 50 million people and has no cure to date. One of its major neuropathological hallmarks is the presence of senile plaques—formed from Amyloid-β (Aβ) oligomers. Aβ has also been associated with the development of cellular senescence in preclinical AD models, suggesting that cellular senescence may be mechanistically involved in disease progression. Cellular senescence is a stress response that occurs when cells are exposed to degenerative factors that puts them into permanent cell cycle arrest, this process increases with age. Apolipoprotein E (ApoE) …

Somatic Inhibition By Microscopic Magnetic Stimulation, Hui Ye

Biology: Faculty Publications and Other Works

Electric currents can produce quick, reversible control of neural activity. Externally applied electric currents have been used in inhibiting certain ganglion cells in clinical practices. Via electromagnetic induction, a miniature-sized magnetic coil could provide focal stimulation to the ganglion neurons. Here we report that high-frequency stimulation with the miniature coil could reversibly block ganglion cell activity in marine mollusk Aplysia californica, regardless the firing frequency of the neurons, or concentration of potassium ions around the ganglion neurons. Presence of the ganglion sheath has minimal impact on the inhibitory effects of the coil. The inhibitory effect was local to the …

The Neurological Asymmetry Of Self-Face Recognition, Aleksandra Janowska, Brianna Balugas, Matthew Pardillo, Victoria Mistretta, Katherine Chavarria, Janet Brenya, Taylor Shelansky, Vanessa Martinez, Kitty Pagano, Nathira Ahmad, Samantha Zorns, Abigail Straus, Sarah Sierra, Julian Keenan

Department of Biology Faculty Scholarship and Creative Works

While the desire to uncover the neural correlates of consciousness has taken numerous directions, self-face recognition has been a constant in attempts to isolate aspects of self-awareness. The neuroimaging revolution of the 1990s brought about systematic attempts to isolate the underlying neural basis of self-face recognition. These studies, including some of the first fMRI (functional magnetic resonance imaging) examinations, revealed a right-hemisphere bias for self-face recognition in a diverse set of regions including the insula, the dorsal frontal lobe, the temporal parietal junction, and the medial temporal cortex. In this systematic review, we provide confirmation of these data (which are …

Mitochondrial Distribution Of Glycine Receptors In Motor Neuron Cell Lines, Katsiaryna Milashevich

Student Theses and Dissertations

Although non-essential, glycine plays an important role in major metabolic reactions and is most known for its anti-inflammatory effects. An accumulation of contemporary research has shown that glycine is able to stabilize membrane potential using glycine receptors at the cellular level and to protect mitochondrial function directly, whether it is from inflammation, heavy metal poisoning, or ischemia-induced neuroinflammation. In this research, the existence of a hypothetical mitochondrial glycine receptor is examined. Immunofluorescence imaging was used to examine the presence of the glycine receptor subunits alpha 1 and alpha 2 in both non- differentiated and differentiated neuroblastoma cell lines. The preliminary …

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 …

Using Zebrafish To Elucidate The Expression And Gene Regulatory Network Of The Genomic Screen Homeobox Transcription Factors And Bring Innovative Science Learning Experiences To West Virginia, Rebecca Ann Coltogirone

Graduate Theses, Dissertations, and Problem Reports (ETD)

Central nervous system (CNS) development requires a code of regionally expressed transcription factors that impart initial neuronal cell identity, connectivity, and function. The absence of a transcription factor code would eliminate the neurodevelopmental logic producing diverse cell types in the CNS. Furthermore, early disruptions in transcription factor expression can affect later connectivity and function of neuronal circuits mediating sensory processing, defects in which are often observed as comorbid with various neurodevelopmental disorders (NDDs). Characterizing transcription factor expression and function is therefore an essential step in discerning the molecular mechanisms underlying human NDDs. genomic screen homeobox 1 and 2 (gsx1 …

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 …

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 …

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 …

Generation And Characterization Of A Rack1 Knockout Cell Line, Roy Missall

Seton Hall University Dissertations and Theses (ETDs)

The µ-opioid receptor (MOR) is an important regulator of nociception, bearing the largest role in analgesia of all opioid receptors. This function has made MOR an effective drug-target for the clinical treatment of pain. However, opioid drugs such as morphine and fentanyl are highly addictive, and prolonged abuse can be fatal due to respiratory depression. A key determinant in the cellular and systemic responses to opioids is MOR. At the transcriptional level, MOR is positively regulated by the transcription factors, including poly-C binding protein 1 (PCBP1). Using the two-hybrid screening, PCBP1 was found to interact with receptor for activated C …

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 …

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, …

Combination Of Investigational Cell-Based Therapy And Deep Brain Stimulation To Alter The Progression Of Parkinson’S Disease, Nader El Seblani

Theses and Dissertations--Pharmacy

Parkinson’s disease (PD) is the second most common neurodegenerative disorder and the motor symptoms are caused by progressive loss of midbrain dopamine neurons. There is no current treatment that can slow or reverse PD. Our current “DBS-Plus” clinical trial (NCT02369003) features the implantation in vivo of autologous Schwann cells (SCs) derived from a patient’s sural nerve into the substantia nigra pars compacta (SNpc) in combination with Deep Brain Stimulation (DBS) therapy for treating patients with advanced PD.

The central hypothesis of our research is that transdifferentiated SCs within conditioned nerve tissue will deliver pro-regenerative factors to enhance the survival of …

Characterizing The Requirements For The Matricellular Protein, Dccn, In Nervous System Function, Elizabeth L. Catudio Garrett

Graduate Student Theses, Dissertations, & Professional Papers

The brain is organized as a complex network of specialized neurons that communicate via a combination of electrical and chemical signals. Our brains function to generate movement, control organ function, or direct complex behaviors; all of which requires the ability to regulate the flow of communication between circuits and networks. Work in this thesis addresses two areas of neuron communication: first, how does the release of more than one neurotransmitter from a single neuron impact behavior, and second, are matricellular proteins (MCPs) key contributors to synaptic transmission and neuron function? The conserved CCN family of MCPs have a …

Neuroanatomy Of The Blackspotted Rockskipper, Entomacrodus Striatus, Pooja Dayal

Williams Honors College, Honors Research Projects

Here I characterized the central neuroanatomy of the Blackspotted Rockskipper, Entomacrodus striatus, native to French Polynesia. The neuroanatomy of E. striatus has not been studied prior to this paper. I used several histology and antibody staining techniques to accomplish this, including Crystal Violet, immunohistochemistry, immunofluorescence, and Bielschowsky’s Silver Nitrate staining. This paper describes the most successful techniques used, identifies major structures in the species’ neuroanatomy, and also explains why studying E. striatus is important in the future of vertebrate research.

Non-Invasive Method For Leptin Supplementation In Zebrafish (Danio Rerio), Regan Mcnamara

Williams Honors College, Honors Research Projects

I tested the hypothesis that recombinant leptin protein can be introduced to zebrafish in vivo through non-invasive soaking in a solution containing the protein. One way to study various molecules’ effects in vivo is through intraperitoneal or intracerebroventricular injections during the embryonic or larval stage, which is invasive, difficult to administer, and can have a high mortality rate. 48 hours post fertilization (hpf) zebrafish were soaked in a His-tagged recombinant leptin protein solution at 10 nM and 100 nM concentrations (produced by Genscript). After soaking, zebrafish larvae were washed extensively to remove all recombinant protein on their exterior before homogenization. …

Assessing Morphology Of Iprgcs After Traumatic Brain Injury, Brian Foresi, Matt Smith

Williams Honors College, Honors Research Projects

ipRGCs are retinal ganglion cells that project to visual processing centers of the brain for nonimage forming visual functions. The relation of ipRGCs to tramatic brain injury (TBI) is emerging as data has been published describing ipRGC functional changes in TBI affected military veterans. Major symptomologies of concussions, a mild form of TBI, also overlap with the function governed by sites in the brain with major ipRGC projection percentages. Assesing if a morphological change is occuring in the ipRGCs after a TBI could support the idea of a pathological mechanism of the injury. This study could also indicate further relevance …

Understanding Object Motion Encoding In The Mammalian Retina., Victor Julian Depiero

Electronic Theses and Dissertations

Phototransduction, transmission of visual information down the optic nerve incurs delays on the order of 50 – 100ms. This implies that the neuronal representation of a moving object should lag behind the object’s actual position. However, studies have demonstrated that the visual system compensates for neuronal delays using a predictive mechanism called phase advancing, which shifts the population response toward the leading edge of a moving object’s retinal image. To understand how this compensation is achieved in the retina, I investigated cellular and synaptic mechanisms that drive phase advancing. I used three approaches, each testing phase advancing at a …

The Functional Conservation Of Frazzled In Insects, Benjamin Wadsworth

Graduate Theses and Dissertations

Axons in the developing embryo receive and react to signals that direct their growth to reach target tissues at specified locations. The signal pathways that direct midline crossing of axons during embryonic development have been comprehensively examined in the past years using the Drosophila ventral nerve cord or the spinal cord as a model system. A number of these signaling mechanisms are conserved, however disparities have been found between species in general strategy or the molecular signals controlling the response of axons to guidance cues.

The Netrin-Frazzled pathway has been shown to aid in midline crossing of axons in the …

Comparison Of Nickel And Cobalt Induced Hypoxic Cell Models Using Cell Proliferation Assay, Melissa Delcasale

Seton Hall University Dissertations and Theses (ETDs)

Hypoxia is an imbalance in oxygen delivery and oxygen consumption, ultimately affecting cell survival. Low levels of oxygen diminish adenosine triphosphate synthesis resulting from a decline in oxidative phosphorylation in the mitochondria, therefore inducing apoptosis and cell death. To create a hypoxia mimicked environment, we used hypoxia mimetic compounds cobalt and nickel to treat human neuroblastoma (NMB) cells. Using hypoxic mimic human neuronal cell models, we examined and compared the effects of compound-induced hypoxia on NMB cell proliferation. The cells were treated with 100mM and 300mM concentrations of each compound at 24- and 48-hour intervals. To investigate cell proliferation, the …

Detecting The Cold: Do Innexins Function In Cold Nociception?, Rachel Barborek

Senior Honors Projects, 2010-2019

Nociception is the perception of and response to harmful stimuli. Nociception is essential for minimizing tissue damage, but aberrant nociceptive pathways can result in chronic pain. Chronic pain in the U.S. is commonly managed with wide-acting opioids, and precisely defining the components of nociceptive pathways could uncover novel targets for pain therapies. I hypothesize that the vitally quick process of nociception would utilize electrical synapses because they transmit signals between neurons more quickly than chemical synapses do. This study, therefore, aims to uncover the potential role of the eight Drosophila melanogaster gap junction proteins, the Innexins, in cold nociception. Wild …

The 5-Ht1a-R Knockout Mouse As A Model Of Later Life Anxiety Disorders: Implications For Sex Differences, Tatyana Budylin

Dissertations, Theses, and Capstone Projects

Anxiety affects nearly twice as many women as it affects men across all cultures and economic groups. Importantly, girls have a higher chance of inheriting anxiety disorders than boys, and many anxiety disorders appear at a very young age. However, little is known about sex differences in brain and behavioral development and how they relate to anxiety in adulthood. Serotonin 1A receptor (5-HT_1A-R) mediated signaling has been implicated in depression and anxiety, however most studies that focus on the involvement of the 5-HT_1A-R have been conducted in adults. Little is known about how the 5-HT_{1A …}