Molecular and Cellular Neuroscience Commons^™

Mapping Molecular Datasets Back To The Brain Regions They Are Extracted From: Remembering The Native Countries Of Hypothalamic Expatriates And Refugees, Arshad M. Khan, Alice H. Grant, Anais Martinez, Gully Apc Burns, Brendan S. Thatcher, Vishwanath T. Anekonda, Benjamin W. Thompson, Zachary S. Roberts, Daniel H. Moralejo, James E. Blevins

Arshad M. Khan, Ph.D.

Ephrinb3 Modulates Hippocampal Neurogenesis And The Reelin Signaling Pathway In A Pilocarpineinduced Model Of Epilepsy, Tian-Tian Liu, Yi Li, Yi Shu, Bo Xiao, Li Feng

Open Access Articles

EphrinB3 is important in the regulation of cell proliferation, differentiation and migration via cellcell contact, and can activate the reelin pathway during brain development. However, the effect of ephrinB3 on hippocampal neurogenesis and the reelin pathway in epilepsy remains to be fully elucidated. In the present study, the expression of ephrinB3 in pilocarpineinduced status epilepticus (SE) rats was investigated. SYBR Greenbased reverse transcriptionquantitative polymerase chain reaction analysis, immunohistochemical labeling and western blot analysis were used to detect the gene and protein expression levels of ephrinB3 and reelin pathway proteins. Immunofluorescence staining of doublecortin (DCX) was utilized to analyze hippocampal neurogenesis ...

Exploiting Click-Chemistry And Microfluidics To Map The Neuronal Itinerary Of App Processing And Amyloid-Beta Generation, Namratha Srinivas

Engineering and Applied Science Theses & Dissertations

Alzheimer’s disease (AD) is a chronic neurodegenerative disease and is the sixth leading cause of death in the United States with approximately 5.5 million Americans diagnosed with it. The neuropathological hallmark includes extracellular senile plaques and intraneuronal neurofibrillary tangles. Recent GWAS studies have identified genes associated with AD, and have revealed several classes of genes implicated in disease pathogenesis. In particular, three general pathways associated with an increased risk of AD included: 1) cholesterol metabolism, innate immune system, and the membrane trafficking. Our lab has focused on intracellular trafficking as it relates to the processing of amyloid precursor ...

Expression Of An Arc-Immunoreactive Protein In The Adult Zebrafish Brain Increases In Response To A Novel Environment, Robert A. Mans, Kyle D. Hinton, Amanda E. Rumer, Kourtnei A. Zellner, Emily A. Blankenship, Lia M. Kerkes, Michael J. Hamilton, Theresa R. Reilly, Cicely H. Payne

Georgia Journal of Science

Zebrafish are a powerful research tool in the field of neuroscience, offering several logistical and physiological advantages over rodents as a research model. However, the molecular dynamics of this model organism, especially with regards to learning and memory, are scarcely known. The current study explored the zebrafish brain for the presence of a protein bearing a similar function to the activity-regulated, cytoskeleton-associated protein (Arc), a critical player in synaptic plasticity. The adult zebrafish brain was found to express a protein with immunoreactivity against the anti-Arc antibody H-300. Immunoreactivity was detected ubiquitously, especially in areas known as adult progenitor cell zones ...

Ethical Analysis Of Brain Augmentation Through Nanotechnology, Austin Caras, James Dejesus

Sound Decisions: An Undergraduate Bioethics Journal

The use of nanoparticles for drug delivery and neural cell manipulation may soon allow for organic and electronic brain augmentations. Medical technology being used for cognitive enhancement brings a host of ethical questions related to safety, justice, privacy, and individuality. Issues concerning medical consent and intellectual property will be skewed as neuroscience expands our understanding of the brain, growing our capacity to read and modify it. Socioeconomic strata may realign based on augmentations and employment opportunities may become dependent on specific cognitive enhancements. Long-term effects of unregulated nanoparticle usage could elicit an environmental or human health disaster. The potential ...

Spinal Cord Trauma: An Overview Of Normal Structure And Function, Primary And Secondary Mechanisms Of Injury, And Emerging Treatment Modalities, Daniel Morin

Senior Honors Theses

The structures of the spinal cord and vertebral column are designed to provide flexibility, while still providing ample protection for the spinal cord deep within. While it does offer remarkable protection against most routine trauma, the spinal cord is still vulnerable to high-force etiologies of trauma and may become damaged as a result. These events are referred to as primary injury. Following the initial injury, the body’s own physiological responses cause a cascade of deleterious effects, known as secondary injury. Secondary injury is a major therapeutic target in mitigating the effects of spinal cord injury (SCI), and much research ...

Inhibition Of Tnf-Alpha Decreases Microglia Activation In Rats Neonatally Treated With Poly I:C, Heath W. Shelton, Russell W. Brown

Appalachian Student Research Forum

Introduction: Current medical treatment for individuals diagnosed with schizophrenia (SCHZ) primarily relies on the inhibition of the dopamine D₂ receptor that has been shown to be supersensitive in these patients. Treatment occurs through the use of antipsychotic medication which leads to a number of debilitating dose-dependent side effects, such as weight gain, agranulocytosis, and seizures. Patients diagnosed with SCHZ have also been shown to have increased inflammation in their central nervous system (CNS), particularly within specific brain regions such as the prefrontal cortex and hippocampus. This is in large part due to the interaction between a pro-inflammatory cytokine called ...

Neutrophils In The Geniculate Ganglion Following Chorda Tympani Transection In Adult Rats, Carlos Vera-Esquivel

Student Research and Creative Activity Fair

Neutrophils in the Geniculate Ganglion Following Chorda Tympani Transection in Adult Rats

The chorda tympani nerve (CT) innervates taste buds on the tongue. The CT’s cell bodies are in the geniculate ganglion (GG). Previous work in our lab found that severing the CT (CTX) results in a reduction of taste bud numbers, and substantial immune responses at the tongue and in the brain. However, there is limited information on how the immune system responds at the GG following CTX. Neutrophils are critical members of the first wave of immune response to nerve injury, attacking foreign pathogens and clearing debris ...

Rescue Of Neocortical Circuit Deficits With Modified Bone Marrow-Derived Mesenchymal Stem Cells, Sb623, In A Rat Model Of Photothrombotic Stroke, Alexander Urry

Yale Day of Data

The following poster characterizes the effects of a novel stem cell line on treating the neural circuit deficits resulting from stroke.

The Lrrk2 Variant E193k Prevents Mitochondrial Fission Upon Mpp+ Treatment By Altering Lrrk2 Binding To Drp1, Maria Perez Carrion, John E. Landers, Stefano Goldwurm, Giovanni Piccoli

Open Access Articles

Mutations in leucine-rich repeat kinase 2 gene (LRRK2) are associated with familial and sporadic Parkinson's disease (PD). LRRK2 is a complex protein that consists of multiple domains, including 13 putative armadillo-type repeats at the N-terminus. In this study, we analyzed the functional and molecular consequences of a novel variant, E193K, identified in an Italian family. E193K substitution does not influence LRRK2 kinase activity. Instead it affects LRRK2 biochemical properties, such as phosphorylation at Ser935 and affinity for 14-3-3epsilon. Primary fibroblasts obtained from an E193K carrier demonstrated increased cellular toxicity and abnormal mitochondrial fission upon 1-methyl-4-phenylpyridinium treatment. We found that ...

Mechanisms Underlying Serotonergic Excitation Of Callosal Projection Neurons In The Mouse Medial Prefrontal Cortex, Emily K. Stephens, Arielle L. Baker, Allan T. Gulledge

Open Dartmouth: Faculty Open Access Articles

Serotonin (5-HT) selectively excites subpopulations of pyramidal neurons in the neocortex via activation of 5-HT_2A (2A) receptors coupled to G_q subtype G-protein alpha subunits. G_q-mediated excitatory responses have been attributed primarily to suppression of potassium conductances, including those mediated by K_V7 potassium channels (i.e., the M-current), or activation of non-specific cation conductances that underlie calcium-dependent afterdepolarizations (ADPs). However, 2A-dependent excitation of cortical neurons has not been extensively studied, and no consensus exists regarding the underlying ionic effector(s) involved. In layer 5 of the mouse medial prefrontal cortex, we tested potential mechanisms of ...

Transcription Factor Pebbled/Rreb1 Regulates Injury-Induced Axon Degeneration, Jonathan E. Farley, Thomas C. Burdett, Romina Barria, Lukas J. Neukomm, Kevin P. Kenna, John E. Landers, Marc R. Freeman

GSBS Student Publications

Genetic studies of Wallerian degeneration have led to the identification of signaling molecules (e.g., dSarm/Sarm1, Axundead, and Highwire) that function locally in axons to drive degeneration. Here we identify a role for the Drosophila C2H2 zinc finger transcription factor Pebbled [Peb, Ras-responsive element binding protein 1 (RREB1) in mammals] in axon death. Loss of Peb in Drosophila glutamatergic sensory neurons results in either complete preservation of severed axons, or an axon death phenotype where axons fragment into large, continuous segments, rather than completely disintegrate. Peb is expressed in developing and mature sensory neurons, suggesting it is required to ...

Validating The Use Of Dreadds In The Study Of The Paraventricular Thalamus (Pvt) And Its Role As In Interface Of Circadian Information, Luke Millisor

Undergraduate Honors Theses

How the brain and body coordinate the phase of their internal clocks has remained elusive despite years of study. The discovery of clock genes showed how individual cells can keep time. The establishment of the suprachiasmatic nucleus as the master clock showed that in normal circumstances the brain relies on one nucleus to communicate time of day information to the rest of the body and brain. By what method the SCN accomplishes this is largely unknown. Glucocorticoid hormones are known to have a role in this communication, but evidence remains for a neuronal pathway between the SCN and extra SCN ...

Chronic Clozapine Treatment Impairs Functional Activation Of Metabotropic Glutamate Receptor 2 Via An Hdac2-Depedent Mechanism, Travis M. Cuddy

Theses and Dissertations

Schizophrenia is a chronic mental disorder affecting millions worldwide. It has no known cure. Current pharmaceutical treatments have shown efficacy in only one of the three symptom clusters of schizophrenia, providing little or no benefit in the other two. Furthermore, the current standard-of-care drugs, known as atypical antipsychotics, carry risks of severe side effects affecting multiple body systems. Most patients opt to discontinue drug therapy within two years of initiation due to lack of efficacy and/or preponderance of adverse effects. Previous findings have shown that chronic usage of atypical antipsychotics causes a 5-HT_2A-dependent upregulation of histone deacetylase ...

Prior Voluntary Wheel Running Prevents Memory Deficits And Enhanced Neuropathic Pain Presenting After Morphine Dosing Ceases, Nathan Plattner

Undergraduate Honors Theses

Clinical research studies show that chronic pain is a prevalent, difficult affliction to manage. The most common management for chronic pain is opioids, which research is showing to paradoxically induce persistent, worsened pain states as well as potentially having negative effects on memory. The necessity for understanding chronic pain and drug management options is apparent, and research is aiming to do just that. Exercise is one potential preventative measure or post hoc treatment possibility for chronic pain, as abundant research has shown. Knowledge of the interactions between exercise, morphine dosing, and peripheral nerve injury is nonexistent. As such, we desired ...

The Transcription Factor Pebbled/Rreb1 Regulates Injury-Induced Axon Degeneration, Jonathan E. Farley

GSBS Dissertations and Theses

Neurons establish complex networks within the nervous system allowing for rapid cell-cell communication via their long, thin axonal processes. These wire-thin projections are susceptible to a number of insults or injuries, and axonal damage can lead to disruption in signal propagation and an overall dysfunction of the neural network. Recent research focused on investigating the underlying mechanisms of injury-induced axon degeneration led to the discovery of a number of endogenous, pro-degenerative molecules such as dSarm/Sarm1, Highwire/Phr1, and Axundead. These signaling molecules are thought to execute axon degeneration in response to injury locally within the distal severed axon, but ...

Disc1 Modulates Neuronal Stress Responses By Gate-Keeping Er-Mitochondria Ca(2+) Transfer Through The Mam, Sung Jin Park, Su Been Lee, Yeongjun Suh, Su-Jeong Kim, Namgyu Lee, Ji-Ho Hong, Cana Park, Youngsik Woo, Koko Ishizuka, Joung-Hun Kim, Per-Olof Berggren, Akira Sawa, Sang Ki Park

Open Access Articles

A wide range of Ca(2+)-mediated functions are enabled by the dynamic properties of Ca(2+), all of which are dependent on the endoplasmic reticulum (ER) and mitochondria. Disrupted-in-schizophrenia 1 (DISC1) is a scaffold protein that is involved in the function of intracellular organelles and is linked to cognitive and emotional deficits. Here, we demonstrate that DISC1 localizes to the mitochondria-associated ER membrane (MAM). At the MAM, DISC1 interacts with IP3R1 and downregulates its ligand binding, modulating ER-mitochondria Ca(2+) transfer through the MAM. The disrupted regulation of Ca(2+) transfer caused by DISC1 dysfunction leads to abnormal Ca ...

Mitochondrial Fission After Traumatic Brain Injury, Tara Fischer

UT GSBS Dissertations and Theses (Open Access)

Mitochondrial dysfunction is a central feature in the pathophysiology of Traumatic Brain Injury (TBI). Loss of mitochondrial function disrupts normal cellular processes in the brain, as well as impedes the ability for repair and recovery, creating a vicious cycle that perpetuates damage after injury. To maintain metabolic homeostasis and cellular health, mitochondria constantly undergo regulated processes of fusion and fission and functionally adapt to changes in the cellular environment. An imbalance of these processes can disrupt the ability for mitochondria to functionally meet the metabolic needs of the cell, therefore resulting in mitochondrial damage and eventual cell death. Excessive fission ...

Analytical Modeling Of A Communication Channel Based On Subthreshold Stimulation Of Neurobiological Networks, Alireza Khodaei

Computer Science and Engineering: Theses, Dissertations, and Student Research

The emergence of wearable and implantable machines manufactured artificially or synthesized biologically opens up a new horizon for patient-centered health services such as medical treatment, health monitoring, and rehabilitation with minimized costs and maximized popularity when provided remotely via the Internet. In particular, a swarm of machines at the scale of a single cell down to the nanoscale can be deployed in the body by the non-invasive or minimally invasive operation (e.g., swallowing and injection respectively) to perform various tasks. However, an individual machine is only able to perform basic tasks so it needs to exchange data with the ...

Targeted Genetic Screen In Amyotrophic Lateral Sclerosis Reveals Novel Genetic Variants With Synergistic Effect On Clinical Phenotype, Pamela J. Shaw, Kevin P. Kenna, John E. Landers

Open Access Articles

Amyotrophic lateral sclerosis (ALS) is underpinned by an oligogenic rare variant architecture. Identified genetic variants of ALS include RNA-binding proteins containing prion-like domains (PrLDs). We hypothesized that screening genes encoding additional similar proteins will yield novel genetic causes of ALS. The most common genetic variant of ALS patients is a G4C2-repeat expansion within C9ORF72. We have shown that G4C2-repeat RNA sequesters RNA-binding proteins. A logical consequence of this is that loss-of-function mutations in G4C2-binding partners might contribute to ALS pathogenesis independently of and/or synergistically with C9ORF72 expansions. Targeted sequencing of genomic DNA encoding either RNA-binding proteins or known ALS ...