Biology Commons^™

Gene Regulatory Pathways Driving Central Nervous System Regeneration In Zebrafish, Ishwariya Venkatesh

Theses and Dissertations

Damage to the central nervous system (CNS) circuitry of adult mammals results in permanent disability. In contrast, the ability to regenerate damaged CNS nerves and achieve functional recovery occurs naturally in fish. The ability of fish to successfully regrow damaged CNS nerves is in part a consequence of their ability to re-express key neuronal growth-associated genes/proteins in response to CNS injury. On such protein is Growth-Associated Protein-43 (Gap43), a protein which is highly enriched in axonal growth cones during CNS development and regeneration. Experiments conducted in mammals have demonstrated that ectopic expression of GAP-43 improves axonal re-growth after injury. Using …

Neurogenic Stem Cells Have The Capacity To Disperse Widely And Fuse With Host Neurons In Adult Rats, Kerry Thompson, Emily Kimes, Michele Kanemori, Daniella Amri, Ashley Noone, Jerika Barron, Ashley Saito, Omar Cortez-Toledo, Ellie Cortez-Toledo, David Arrizon, Johanna Quist, Yohualli Balderas, Melissa Miranda, Tina Tran, Frances Kim

Kerry Thompson

No abstract provided.

Acrolein As A Novel Therapeutic Target For Spinal Cord Injury Induced Neuropathic Pain, Jonghyuck Park

Open Access Dissertations

Despite years of research, post-spinal cord injury (SCI) chronic neuropathic pain remains refractory to treatment and drastically impairs quality of life for SCI victims beyond paralysis. Although inflammation and free radicals contribute to neuropathic pain in SCI, the mechanism is not completely clear. We have recently demonstrated that acrolein, a product and catalyst of lipid peroxidation, induces a vicious cycle of oxidative stress, amplifying its effects and perpetuating oxidative stress and inflammation. In the current study, we have confirmed that acrolein is elevated significantly at least two weeks post-SCI which coincides with the emergence of hyperalgesia (mechanical, cold and thermal). …

Nano-Engineered Polymers In Drug Delivery: Potential Approaches For Attenuation Of Secondary Injury After Spinal Cord Trauma, Wen Gao

Open Access Dissertations

Secondary injury elicits a complex series of pathophysiological events after the primary spinal cord trauma and even after its implantation treatment for neural functional recovery. These secondary injuries include an up-regulation of glial cells associated reactive oxygen species, nitrogen species, and reactive astrogliosis, and they can result in various levels of cellular and tissue damage. The inhibition of them has been proved to lead to functional recovery of the spinal cord. In this study, we concentrated on developing polymers and nano-techniques based drug delivery strategies to eliminate these secondary injuries. ^ To maintain and improve the performance of the implants …

Quantitative Modeling Of Spatiotemporal Systems: Simulation Of Biological Systems And Analysis Of Error Metric Effects On Model Fitting, James Hengenius

Open Access Dissertations

Understanding the biophysical processes underlying biological and biotechnological processes is a prerequisite for therapeutic treatments and technological innovation. With the exponential growth of computational processing speed, experimental findings in these fields have been complemented by dynamic simulations of developmental signaling and genetic interactions. Models provide means to evaluate "emergent" properties of systems sometimes inaccessible by reductionist approaches, making them test beds for biological inference and technological refinement.^ The complexity and interconnectedness of biological processes pose special challenges to modelers; biological models typically possess a large number of unknown parameters relative to their counterparts in other physical sciences. Estimating these parameter …

Developing A Practical Wireless Monitoring Solution For A Size-Constrained, Low-Power, Biomechanical, Sports Telemetry System, Jeffery Ray King

Open Access Theses

As sport-related concussions become more prevalent, the ability to quickly and reliably assess brain injury risk is increasingly essential. Commercially-available systems exist with the goal of assessing the risk of traumatic brain injury in athletes in real-time. These systems utilize a pre-determined acceleration threshold, discarding all captured information below this arbitrary threshold. The use of an event-based model to assess the risk of traumatic brain injury has been shown to be inadequate. Therefore, these systems falsely promote "accurate" real-time communication of risk. Research conducted by the Purdue Neurotrauma Group (PNG) seeks to advance the field by developing a biomechanical sports …

Morphometric Characterization Of Individual Sympathetic Postganglionic Axons Innervating The Muscle Layers Of The Gastrointestinal Tract Of The Rat: A Complex Effector Model, Gary C. Walter

Open Access Dissertations

A full description of the terminal morphology of sympathetic postganglionic axons innervating the musculature of the gastrointestinal (GI) tract has not been available. Furthermore, common assumptions about the morphology and distribution of catecholaminergic terminal fields have been strongly shaped by the limitations of the techniques employed to distinguish the fibers and complicated by inconsistent findings generated with various methodologies. Thus, the present experiment used modern neural tracer techniques to provide high-resolution labeling of sympathetic fibers projecting to the smooth muscle wall of the GI tract. Fischer 344 rats (N = 50) received injections of dextran biotin into the left …

Lights And Larvae: Using Optogenetics To Teach Recombinant Dna And Neurobiology, John Titlow, Heidi Anderson, Robin L. Cooper

Biology Faculty Publications

Switching genes between organisms and controlling an animal’s brain using lasers may seem like science fiction, but with advancements in a technique called optogenetics, such experiments are now common in neuroscience research. Optogenetics combines recombinant DNA technology with a controlled light source to help researchers address biomedical questions in the life sciences. The technique has gained the most traction in neurobiology—the biology of the nervous system—where specific wavelengths of light are used to control or measure the activity of neurons in transgenic organisms (i.e., those with artificially inserted genes).

These optical recording and stimulation techniques are used in nervous system …

Long-Term Cre-Mediated Retrograde Tagging Of Neurons Using A Novel Recombinant Pseudorabies Virus, Hysell V. Oviedo, Hassasna K. Oyibo, Petr Znamenskiy, Lynn W. Enquist, Anthony M. Zador

Publications and Research

Brain regions contain diverse populations of neurons that project to different long-range targets. The study of these subpopulations in circuit function and behavior requires a toolkit to characterize and manipulate their activity in vivo. We have developed a novel set of reagents based on Pseudorabies Virus (PRV) for efficient and long-term genetic tagging of neurons based on their projection targets. By deleting IE180, the master transcriptional regulator in the PRV genome, we have produced a mutant virus capable of infection and transgene expression in neurons but unable to replicate in or spread from those neurons. IE180-null mutants showed no cytotoxicity, …

Discovery And Elucidation Of The Fgfr3-Tacc3 Recurrent Fusion In Glioblastoma, Brittany C. Parker Kerrigan

Dissertations & Theses (Open Access)

Fusion genes occur due to chromosomal instability where two previously separate genes rearrange and fuse together, forming a hybrid gene. The first fusions were reported in leukemias; however, with the advent of more powerful sequencing technologies, fusions have recently been reported in several solid tumors. Using next-generation deep sequencing approaches, we discovered a fusion gene connecting the fibroblast growth factor receptor 3 (FGFR3) gene to the transforming coiled-coil containing protein 3 (TACC3) gene in glioblastoma multiforme. The fusion occurred in 8.3% of patient samples, but not in low grade or normal samples. FGFR3-TACC3 produced an in-frame …

Fty720 (Fingolimod) Provides Insight Into The Molecular Mechanisms Of Multiple Sclerosis, Madelyn Elizabeth Crawford

Pursuit - The Journal of Undergraduate Research at The University of Tennessee

Multiple sclerosis (MS) is a neurodegenerative disorder caused by a prolonged immune- mediated inflammatory response that targets myelin. Nearly all of the drugs approved for the treatment of MS are general immunosuppressants or only function in symptom management. The oral medication fingolimod, however, is reported to have direct therapeutic effects on cells of the central nervous system in addition to immunomodulatory functions. Fingolimod is known to interact with sphingosine-1-phosphate (S1P) receptors, and the most widely- accepted theory for its mechanism of action is functional antagonism of the receptor. This review examines significant neuromodulatory effects achieved by functional antagonism of the …

Associations Between Hypothalamic-Pituitary-Adrenal Axis System Gene Variants And Cortisol Reactivity In Preschoolers: Main Effects And Gene-Environment Interactions, Haroon I. Sheikh

Electronic Thesis and Dissertation Repository

Exposure to stressful events during early development has consistently been shown to produce long lasting effects on the hypothalamic-pituitary-adrenal (HPA) axis, which may increase vulnerability to mood and anxiety disorders. Recently reported genetic association studies indicate that these disorders may be influenced, in part, by gene-environment interactions (GxE) involving polymorphisms within the corticotrophin-releasing hormone and monoaminergic system genes. However, little is known about how genetic variants and life stress work to shape children’s neuroendocrine reactivity and emerging symptoms. Therefore, the aim of this thesis is to examine main effects of candidate genes and GxE on the neuroendocrine stress response and …

Determining A Correlation Between Individual Differences In Eye Movements And Working Memory, Mackenzie Sunday

Senior Theses

This study determined if a relationship exists between individual differences in eye movements and working memory measures. The eye movement system can provide insight into processes that occur in the mind as well as a better understanding of the relationship between quantifiable aspects of eye movements and the more abstract inner workings of the mind. Recently, consistent and reliable individual differences have been found in individuals’ eye movement behaviors. For example, individuals with longer fixation durations for one visual task have longer fixations across all other visual tasks. The eye movements of participants were collected during four different viewing tasks …

Characterization Of The Ependymal Barrier Due To Human Aging And Injury In Murine Models, Ye Sun

University Scholar Projects

Ventriclulomegaly, or the expansion of the ventricles in the brain, is a phenomenon associated with age and injury to the brain. The ependymal layer that encases the ventricles displays certain degrees of plasticity and regenerative ability due to its associated stem cell niche, the subventricular zone (SVZ). Previous research in the Conover Lab has shown that in the mouse, which maintains an actively proliferating SVZ into adulthood, there is an intact ependymal monolayer throughout normal aging, with maintained lateral ventricle size with some degree of stretching. In contrast, the human SVZ declines in proliferative capacity after infancy, and age-related changes …

The Effect Of Repeated Mild Traumatic Brain Injury On Ventricular Volume And Microglial Activation, Lillian Rose Talbot

Honors Scholar Theses

As the leading cause of death and disability in individuals under the age of 45-years-old, Traumatic Brain Injury (TBI) is a public health crisis that demands the attention of the scientific and medical community [28]. The majority of all TBIs that occur in the United States each year are a non-deadly yet detrimental form of closed brain injury known as mild TBI (mTBI) or concussion [6]. Athletes, young people and military personnel all face a high risk of acquiring mTBI as a result of their environments. In our study we have chosen to model repeated mTBI (rmTBI) in the mouse …

Bidirectional Influence Of Epinephrine On Hippocampal Ltp Via Β-Adrenergic Receptors, Georgia Christine Buscaglia

Honors Capstone Projects - All

The formation and storage of memories within the brain remains a subject that is not well understood. The hippocampus has been identified by many studies as a likely center for memory formation (Lynch, 2004), and further research into this subject has begun to suggest that synaptic plasticity in the hippocampus could be partly responsible for the physical changes in the brain, which underlie memory formation. Long Term Potentiation is a form of synaptic plasticity, and is considered to be a physical increase in the strength of connection between neurons or groups of neurons. Much like memories, the duration of a …

Development Of A System For Analysis Of Muscle Contraction Pattern During Drosophila Melanogaster Crawling Behavior, Mary Catherine Decker

Celebrating Scholarship & Creativity Day (2011-2017)

The aim of this study was to attain footage of the crawling Drosophila larva from 360° angles in order to visualize the pattern of individual muscle contractions. A GAL4-UAS system was used to drive homozygous GCAMP expression, causing the muscles of the Drosophila larva to fluoresce when contracting. A stand was designed in order to place a live, crawling larva in a glass capillary tube under a fluorescent microscope and then rotate the tube completely for 360° video footage. Through the combination of the GCAMP expression and the rotatable stand, video of the individual muscle contraction pattern of a crawling …

The Effects Of Picrotoxin And Ethanol On Crayfish Escape And Central Motor Pattern Neural Circuits, Rebecca Bierman, Nathan Hardcastle, Colin Istvan

Georgia State Undergraduate Research Conference

No abstract provided.

Lipidomic Analysis Of Glioblastoma Multiforme, Soo Jung Ha

Open Access Theses

Glioblastoma Multiforme (GBM) is the most common and malignant form of the primary brain tumor. Due to its highly invasive nature, current treatment options have not been able to improve the survival rate in past 20 years. In order to discover GBM therapeutic targets, omics technologies have been widely used to identify potential biomarkers. ^ This research study focused on investigating lipid biomarkers of human GBM orthotopic mouse models employing mass spectrometry. Human tumor cell lines GBM10 and GBM43 were injected in the right cerebral hemisphere and flank sites in NOD/SCID mice (n = 10 mice per group). Left cerebral …

Positions In The Glun2c-Containing Nmdar Regulate Alcohol Sensitivity And Ion Channel Gating, Man Wu

Master's Theses (2009 -)

The N-methyl-D-aspartate (NMDA) receptor, a subtype of glutamate-gated ion channel, has been shown to be a major target of ethanol in the central nervous system (CNS). Previous studies have identified positions in the third and fourth membrane-associated (M) domains of the NMDAR GluN1 and GluN2A subunits that influence ethanol sensitivity. Among the alcohol sensitive sites, a methionine residue is highly conserved in all GluN1 and GluN2 subunits. We proposed the methionine position (Met-821) in the M4 domain of the GluN2C subunit can regulate ethanol sensitivity and ion channel gating. 14 mutations were made at the methionine position, 7 substitutions yielded …

Kif11 Dependent Cell Cycle Progression In Radial Glial Cells Is Required For Proper Neurogenesis In The Zebrafish Neural Tube, Kimberly Johnson, Chelsea Moriarty, Nessy Tania, Alissa Ortman, Kristina Dipietrantonio, Brittany Edens, Jean Eisenman, Deborah Ok, Sarah Krikorian, Jessica Barragan, Christophe Golé, Michael J.F. Barresi

Mathematics Sciences: Faculty Publications

Radial glia serve as the resident neural stem cells in the embryonic vertebrate nervous system, and their proliferation must be tightly regulated to generate the correct number of neuronal and glial cell progeny in the neural tube. During a forward genetic screen, we recently identified a zebrafish mutant in the kif11 loci that displayed a significant increase in radial glial cell bodies at the ventricular zone of the spinal cord. Kif11, also known as Eg5, is a kinesin-related, plus-end directed motor protein responsible for stabilizing and separating the bipolar mitotic spindle. We show here that Gfap+ radial glial cells express …

The Interplay Of Visual Attention And Saccade Planning In Active Vision, Afsheen Khan

Dissertations, Theses, and Capstone Projects

Vision is a highly active process. When we view the world, we do not hold our eyes still, but constantly move them around in order to view the object or area of interest with the fovea (the region of the retina with the highest acuity). Saccades are the step-like movements that we most often employ for this purpose. In addition, our attention is constantly being covertly attracted or directed to points of interest. Combining these different aspects of viewing: visual processing, the orienting of attention, and eye movements can be referred to as `active vision'.

Most work on active vision …

The Role Of Er-Alpha And The Ovaries In The Enduring Altered Behavioral Response To Pubertal Immune Stress, Bethany Rappleyea

Masters Theses 1911 - February 2014

Peripubertal immune stress alters adult responsiveness to estradiol (E₂) and progesterone (P). When female mice are injected with the bacterial endotoxin lipopolysaccharide (LPS) at six weeks of age, or during pubertal development, they display a decrease in response to ovarian hormones. In contrast, females ovariectomized prior to peripubertal immune stress display typical levels of sexual behavior following sequential injections of E₂ and P in adulthood. Additionally, intact females exposed to peripubertal immune stress display a decrease in estrogen receptor alpha (ER-α)-immunoreactive (ir) cells in the medial preoptic area (MPOA) and ventromedial nucleus of the hypothalamus (VMH) in …

Inducing Task-Relevant Responses To Speech In The Sleeping Brain, Sid Kouider, Thomas Andrillon, Leonardo S. Barbosa, Louise Goupil, Tristan A. Bekinschtein

Biology Faculty Publications

Falling asleep leads to a loss of sensory awareness and to the inability to interact with the environment [1]. While this was traditionally thought as a consequence of the brain shutting down to external inputs, it is now acknowledged that incoming stimuli can still be processed, at least to some extent, during sleep [2]. For instance, sleeping participants can create novel sensory associations between tones and odors [3] or reactivate existing semantic associations, as evidenced by event-related potentials [4; 5; 6 ; 7]. Yet, the extent to which the brain …

Effects Of Early Experience And Plasticity On Neuronal Morphology Within The Prefrontal Cortex In A Rodent Model Of Hypoxia-Ischemia, Zarah M. Melendez

Honors Projects

Hypoxia-ischemia (HI) is low oxygenation to the brain paired with low blood supply that can disrupt normal patterns of brain development. HI injury is characterized by many long-term cognitive and behavioral deficits including working memory. Neuronal plasticity due to early sensory or learning experience has been suggested to facilitate recovery of function after neonatal brain injury. Plasticity is the ability for the nervous system, more specifically neurons, and their synapses to modify their function and morphology due to experiences, which in turn correlate with changes in behavior. The objective of the present study was to investigate the effects of neonatal …

Dopaminergic And Activity-Dependent Modulation Of Mechanosensory Responses In Drosophila Melanogaster Larvae, Josh S. Titlow

Theses and Dissertations--Biology

A central theme of this dissertation is nervous system plasticity. Activity-dependent plasticity and dopaminergic modulation are two processes by which neural circuits adapt their function to developmental and environmental changes. These processes are involved in basic cognitive functions and can contribute to neurological disorder. An important goal in modern neurobiology is understanding how genotypic variation influences plasticity, and leveraging the quantitative genetics resources in model organisms is a valuable component of this endeavor. To this end I investigated activity-dependent plasticity and dopaminergic modulation in Drosophila melanogaster larvae using neurobiological and genetic approaches.

Larval mechanosensory behavior is described in Chapter 2. …

The Postsynaptic Regulation Of Synaptic Strength In Drosophila, Daniel Michael Gertner

Legacy Theses & Dissertations (2009 - 2024)

Postsynaptic Ca2+ plays an important role in synaptic homeostasis and synaptic plasticity. Postsynaptic Ca2+ signals have been shown to regulate synaptic transmission at the Drosophila larval neuromuscular junction (NMJ), however, these signals have not been well characterized. This will explore how these signals regulate synaptic strength and what channels are involved. In previous lab experiments Ca2+ transients were observed during evoked and spontaneous release (Desai and Lnenicka, 2011). It was further demonstrated that a reduction in synaptic strength occurs following synaptic stimulation. It was hypothesized that the increase in postsynaptic Ca2+ following synaptic stimulation activates the gCS and causes a …

Quantification Of Protoporphyrin Ix Accumulation In Glioblastoma Cells – A New Technique, John E Lawrence

Journal Articles

5-Aminolevulinic Acid (5-ALA) is a precursor of heme synthesis. A metabolite, protoporphyrin IX (PpIX), selectively accumulates in neoplastic tissue including glioblastoma. Presurgical administration of 5-ALA forms the basis of fluorescence-guided resection (FGR) of glioblastoma (GBM) tumors. However, not all gliomas accumulate sufficient quantities of PpIX to fluoresce, thus limiting the utility of FGR. We therefore developed an assay to determine cellular and pharmacological factors that impact PpIX fluorescence in GBM. This assay takes advantage of a GBM cell line engineered to express yellow fluorescent protein. Methods. The human GBM cell line U87MG was transfected with a YFP expression vector. After …

Calpain 5: A Non-Classical Calpain Highly Expressed In The Cns And Localized To Mitochondria And Nuclear Pml Bodies, Ranjana Singh

Theses and Dissertations--Neuroscience

Calpain 5 (CAPN5) is a non-classical member of the calpain family. It lacks the EF-hand motif characteristic of the classical calpains, calpain 1 and 2, but retains catalytic and Ca²⁺ binding non EF domains. Tra-3, an ortholog of CAPN5, is involved in necrotic cell death in C.elegans; although specific role of CAPN5 has not been investigated in the mammalian CNS. I compared relative mRNA levels of calpains in rat CNS, which revealed that CAPN5 is the second most highly expressed calpain. We examined relative levels of CAPN5 from late embryonic day 18 to postnatal day 90 and …