Neuroscience and Neurobiology Commons^™

Mechanisms Of Astrocyte Contribution To Bortezomib-Induced Peripheral Neuropathy, Caleb R. Robinson

Dissertations and Theses (Open Access)

Bortezomib is a proteasome inhibitor used in the treatment of multiple myeloma and other non-solid malignancies, alone or in combination with other chemotherapy drugs. Like other chemotherapeutic agents, bortezomib treatment is frequently accompanied by chemotherapy-induced peripheral neuropathy (CIPN) that may be dose-limiting, adversely affecting quality of life and prognosis. The mechanisms behind bortezomib-induced peripheral neuropathy (BIPN) and CIPN overall are largely unknown. Recent findings in other pain models have indicated substantial involvement of glial cells in chronic pain. Although injury models have shown activation of both astrocytes and microglia following insult, research in other CIPN models has shown astrocytic activation …

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

Dissertations and 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 …

The Effect Of Acute Lps-Induced Immune Activation And Brain Insulin Signaling Disruption In A Diabetic Model Of Alzheimer's Disease, Andrew Scott Murtishaw

UNLV Theses, Dissertations, Professional Papers, and Capstones

Alzheimer's disease (AD) is a neurodegenerative disorder marked by progressive cognitive impairments and pathological hallmarks that include amyloid plaques, neurofibrillary tangles, and neuronal loss. Several well-known mutations exist that lead to early-onset familial AD (fAD). However, these cases only account for a small percentage of total AD cases. The vast majority of AD cases are sporadic in origin (sAD) and are less clearly influenced by a single mutation but rather some combination of genetic and environmental risk.

The etiology of sAD remains unclear but numerous risk factors have been identified that increase the chance of developing AD. Among these risk …

Alternating Current And Infrared Produce An Onset-Free Reversible Nerve Block, Emilie H. Lothet, Kevin L. Kilgore, Niloy Bhadra, Narendra Bhadra, Tina Vrabec, Yves T. Wang, Michael W. Jenkins, Hillel J. Chiel

Faculty Scholarship

Nerve block can eliminate spasms and chronic pain. Kilohertz frequency alternating current (KHFAC) produces a safe and reversible nerve block. However, KHFAC-induced nerve block is associated with an undesirable onset response. Optical inhibition using infrared (IR) laser light can produce nerve block without an onset response, but heats nerves. Combining KHFAC with IR inhibition [alternating current and infrared (ACIR)] produces a rapidly reversible nerve block without an onset response. ACIR can be used to rapidly and reversibly provide onset-free nerve block in the unmyelinated nerves of the marine mollusk Aplysia californica and may have significant advantages over either modality alone. …

Neuroinflammation And Neurodegeneration In Adult Rat Brain From Binge Ethanol Exposure: Abrogation By Docosahexaenoic Acid, Nuzhath Tajuddin, Kwan-Hoon Moon, Simon Alex Marshall, Kimberly Nixon, Edward J. Neafsey, Hee-Yong Kim, Michael A. Collins

Pharmaceutical Sciences Faculty Publications

Evidence that brain edema and aquaporin-4 (AQP4) water channels have roles in experimental binge ethanol-induced neurodegeneration has stimulated interest in swelling/edema-linked neuroinflammatory pathways leading to oxidative stress. We report here that neurotoxic binge ethanol exposure produces comparable significant effects in vivo and in vitro on adult rat brain levels of AQP4 as well as neuroinflammation-linked enzymes: key phospholipase A2 (PLA2) family members and poly (ADP-ribose) polymerase-1 (PARP-1). In adult male rats, repetitive ethanol intoxication (3 gavages/d for 4 d, ∼ 9 g/kg/d, achieving blood ethanol levels ∼ 375 mg/dl; "Majchrowicz" model) significantly increased AQP4, Ca+2-dependent PLA2 GIVA (cPLA2), phospho-cPLA2 GIVA …

Inter- And Intralimb Adaptations To A Sensory Perturbation During Activation Of The Serotonin System After A Low Spinal Cord Transection In Neonatal Rats, Misty M. Strain, Sierra D. Kauer, Tina Kao, Michele R. Brumley

Publications and Research

Activation of the serotonin system has been shown to induce locomotor activity following a spinal cord transection. This study examines how the isolated spinal cord adapts to a sensory perturbation during activation of the serotonergic system. Real-time and persistent effects of a perturbation were examined in intact and spinal transected newborn rats. Rats received a spinal surgery (sham or low thoracic transection) on postnatal day 1 and were tested 9 days later. At test, subjects were treated with the serotonergic receptor agonist quipazine (3.0 mg/kg) to induce stepping behavior. Half of the subjects experienced range of motion (ROM) restriction during …

Increasing Maternal Or Post-Weaning Folic Acid Alters Gene Expression And Moderately Changes Behavior In The Offspring, Subit Barua, Kathryn K. Chadman, Salomon Kuizon, Diego Buenaventura, Nathan W. Stapley, Felicia Ruocco, Umme Begum, Sara R. Guariglia, W. Ted Brown, Mohamad Junaid

Publications and Research

Background: Studies have indicated that altered maternal micronutrients and vitamins influence the development of newborns and altered nutrient exposure throughout the lifetime may have potential health effects and increased susceptibility to chronic diseases. In recent years, folic acid (FA) exposure has significantly increased as a result of mandatory FA fortification and supplementation during pregnancy. Since FA modulates DNA methylation and affects gene expression, we investigated whether the amount of FA ingested during gestation alters gene expression in the newborn cerebral hemisphere, and if the increased exposure to FA during gestation and throughout the lifetime alters behavior in C57BL/6J mice.

Methods …

The Effects Of Cognitively Engaging Physical Activity On The Executive Function Of Sixth Graders, Alyssa Michele Humphreys

Theses and Dissertations

This purpose of this study was to examine the effects of cognitively engaging exercise, aerobic exercise, and resting conditions on the executive function of 6th graders. Four conditions were tested: cognitively engaging exercise, repetitive aerobic exercise, cognitively engaging rest, and rest. Executive function was measured by pre and post Stroop tests, which is a test of reaction time and inhibition. Results showed no significant differences between conditions in the choice reaction time test, however the cognitively engaging exercise was significantly different from all other conditions on the Stroop test.

Functional Correlates Of Optic Flow Motion Processing In Parkinson's Disease, Deepti Putcha, Robert S. Ross, Maya L. Rosen, Daniel J. Norton, Alice Cronin-Golomb, David C. Somers, Chantal E. Stern

Neuroscience: Faculty Publications

The visual input created by the relative motion between an individual and the environment, also called optic flow, influences the sense of self-motion, postural orientation, veering of gait, and visuospatial cognition. An optic flow network comprising visual motion areas V6, V3A, and MT+, as well as visuo-vestibular areas including posterior insula vestibular cortex (PIVC) and cingulate sulcus visual area (CSv), has been described as uniquely selective for parsing egomotion depth cues in humans. Individuals with Parkinson's disease (PD) have known behavioral deficits in optic flow perception and visuospatial cognition compared to age- and education-matched control adults (MC). The present study …

Behavioral And Neuroanatomical Abnormalities In Pleiotrophin Knockout Mice, Jason W. Krellman, Henry H. Ruiz, Veronica A. Marciano, Bracha Mondrow, Susan D. Croll

Publications and Research

Pleiotrophin (PTN) is an extracellular matrix-associated protein with neurotrophic and neuroprotective effects that is involved in a variety of neurodevelopmental processes. Data regarding the cognitive-behavioral and neuroanatomical phenotype of pleiotrophin knockout (KO) mice is limited. The purpose of this study was to more fully characterize this phenotype, with emphasis on the domains of learning and memory, cognitive-behavioral flexibility, exploratory behavior and anxiety, social behavior, and the neuronal and vascular microstructure of the lateral entorhinal cortex (EC). PTN KOs exhibited cognitive rigidity, heightened anxiety, behavioral reticence in novel contexts and novel social interactions suggestive of neophobia, and lamina-specific decreases in neuronal …

Proliferation, Migration, And Survival Of Cells In The Telencephalon Of The Ball Python, Python Regius, Thomas B. Bales

Master's Theses

Reptiles exhibit neurogenesis throughout the brain during adulthood. However, very few studies have quantified telencephalon-wide neurogenesis in adulthood, and no studies have performed these investigations in snakes. Quantifying neurogenesis in the adult snake is essential to understanding class-wide adult neurogenesis and providing insight into the evolution of this trait. The thymidine analog 5-bromo-2’-deoxyuridine (BrdU) was used to quantify cell proliferation, migration, and survival in the ball python (Python regius). First, to determine the proper dose of BrdU for injection we subcutaneously injected 50mg/kg, 100mg/kg, and 250mg/kg into 15 adult male P. regius. We found the 250mg/kg dose …

Effects Of Dfo-Induced Hypoxia On Key Signaling Mediators, Jennifer Candelora

Seton Hall University Dissertations and Theses (ETDs)

While diseases such as cancer and diabetes, or surgery and traumatic injury can cause hypoxia through a decrease in blood circulation to bodily regions or decrease cardiac output they can also associate with hypoxia-induced pain. Clinically, opioids, such as morphine, are used to modulate pain. The mu-opioid receptors (MORs) are one of three main types of opioid receptors and are key mediators in morphine-induced analgesia. Therefore, in this study, the effect of hypoxia on MOR gene expression was examined using human neuronal cells treated with DFO to create a hypoxic-mimic condition. We found that MOR expression was shown to decrease …

Particle Swarm Optimization Using Multiple Neighborhood Connectivity And Winner Take All Activation Applied To Biophysical Models Of Inferior Colliculus Neurons, Brandon S. Coventry

Open Access Theses

Age-related hearing loss is a prevalent neurological disorder, affecting as many as 63% of adults over the age of 70. The inability to hear and understand speech is a cause of much distress in aged individuals and is becoming a major public health concern as age-related hearing loss has also been correlated with other neurological disorders such as Alzheimer's dementia. The Inferior Colliculus (IC) is a major integrative auditory center, receiving excitatory and inhibitory inputs from several brainstem nuclei. This complex balance of excitation and inhibition gives rise to complex neural responses, which are measured in terms of firing rate …

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 …

Motor Cortex Electrical Stimulation Augments Sprouting Of The Corticospinal Tract And Promotes Recovery Of Motor Function, Jason B. Carmel, John H. Martin

Publications and Research

The corticospinal system—with its direct spinal pathway, the corticospinal tract (CST) – is the primary system for controlling voluntary movement. Our approach to CST repair after injury in mature animals was informed by our finding that activity drives establishment of connections with spinal cord circuits during postnatal development. After incomplete injury in maturity, spared CST circuits sprout, and partially restore lost function. Our approach harnesses activity to augment this injury-dependent CST sprouting and to promote function. Lesion of the medullary pyramid unilaterally eliminates all CST axons from one hemisphere and allows examination of CST sprouting from the unaffected hemisphere. We …

Unconscious Neural Processing Differs With Method Used To Render Stimuli Invisible, Sergey V. Fogelson, Peter J. Kohler, Kevin J. Miller, Richard Granger, Peter U. Tse

Dartmouth Scholarship

Visual stimuli can be kept from awareness using various methods. The extent of processing that a given stimulus receives in the absence of awareness is typically used to make claims about the role of consciousness more generally. The neural processing elicited by a stimulus, however, may also depend on the method used to keep it from awareness, and not only on whether the stimulus reaches awareness. Here we report that the method used to render an image invisible has a dramatic effect on how category information about the unseen stimulus is encoded across the human brain. We collected fMRI data …

Roles Of Dopamine D1 And D2, Opioid And Glutamate Nmda Receptor Signaling In The Acquisition And Expression Of Fat- And Glucose-Conditioned Flavor Preferences In Rats And C-Fos Analysis Of The Dopamine Mesotelencephalic And Nigrostriatal Pathways Following Intake Of Sugars And Fats In Rats, Julie Dela Cruz

Dissertations, Theses, and Capstone Projects

Systemic administration of the non-competitive NMDA antagonist, MK-801, demonstrated that acquisition, but not expression, were found to affect the orosensory-mediated (flavor/flavor: f/f) fructose-conditioned flavor preference (CFP). The present studies demonstrated a similar outcome when f/f and f/n processes were combined. Fat-CFP and glucose-CFP studies indicated that systemic injections of the NMDA antagonist, MK-801, were able to significantly reduce acquisition, but not expression, of Corn-Oil (CO)-CFP and glucose-CFP. Both studies appear to have mitigated effects on acquisition as compared to the separate orosensory and postingestive CFP studies.

Previous studies found that systemic administration of dopamine (DA) D1 (SCH23390) and D2 (raclopride) …

The Development Of Sleep-Wake Rhythms And The Search For Elemental Circuits In The Infant Brain, Mark S. Blumberg, Andrew J. Gall, William D. Todd

Faculty Publications

Despite the predominance of sleep in early infancy, developmental science has yet to play a major role in shaping concepts and theories about sleep and its associated ultradian and circadian rhythms. Here we argue that developmental analyses help us to elucidate the relative contributions of the brainstem and forebrain to sleep-wake control and to dissect the neural components of sleep-wake rhythms. Developmental analysis also makes it clear that sleep-wake processes in infants are the foundation for those of adults. For example, the infant brainstem alone contains a fundamental sleep-wake circuit that is sufficient to produce transitions among wakefulness, quiet sleep, …

Self-Reported Head Injury And Risk Of Late-Life Impairment And Ad Pathology In An Ad Center Cohort, Erin L. Abner, Peter T. Nelson, Frederick A. Schmitt, Steven R. Browning, David W. Fardo, Lijie Wan, Gregory A. Jicha, Gregory E. Cooper, Charles D. Smith, Allison M. Caban-Holt, Linda J. Van Eldik, Richard J. Kryscio

Sanders-Brown Center on Aging Faculty Publications

Aims: To evaluate the relationship between self-reported head injury and cognitive impairment, dementia, mortality, and Alzheimer's disease (AD)-type pathological changes. Methods: Clinical and neuropathological data from participants enrolled in a longitudinal study of aging and cognition (n = 649) were analyzed to assess the chronic effects of self-reported head injury. Results: The effect of self-reported head injury on the clinical state depended on the age at assessment: for a 1-year increase in age, the OR for the transition to clinical mild cognitive impairment (MCI) at the next visit for participants with a history of head injury was 1.21 and 1.34 …

Seasonal And Sex Differences In The Effects Of Melatonin On Brain Arginine Vasotocin In Green Treefrogs (Hyla Cinerea): Relationship To Melatonin Receptor 1a, Christina Marie Howard

Dissertations and Theses

Critical life history events such as breeding, migration and hibernation must take place in the correct environmental context to minimize deleterious consequences on survival and reproductive fitness. Neuroendocrine mechanisms synchronizing internal physiological states with extrinsic environmental cues are vital to timing life history events appropriately. Secretion of the pineal hormone melatonin is sensitive to light and temperature cues, which provides a physiological indicator of time of day and time of year for organisms. Melatonin influences seasonal reproduction in a variety of vertebrates, likely by altering the synthesis and/or release of reproductive neuropeptides in the brain. The neuropeptides arginine vasotocin and …

Online Tracking Of The Contents Of Conscious Perception Using Real-Time Fmri, Christoph Reichert, Robert Fendrich, Johannes Bernarding, Claus Tempelmann, Hermann Hinrichs, Jochem W. Rieger

Dartmouth Scholarship

Perception is an active process that interprets and structures the stimulus input based on assumptions about its possible causes. We use real-time functional magnetic resonance imaging (rtfMRI) to investigate a particularly powerful demonstration of dynamic object integration in which the same physical stimulus intermittently elicits categorically different conscious object percepts. In this study, we simulated an outline object that is moving behind a narrow slit. With such displays, the physically identical stimulus can elicit categorically different percepts that either correspond closely to the physical stimulus (vertically moving line segments) or represent a hypothesis about the underlying cause of the physical …

Astroglial Boundary Formation And Epha4 Signaling In Neuroblast Migration, Nicholas B. Gallo

University Scholar Projects

Adult neurogenesis, the process of generating new neurons from neural precursors, is a highly complex process that is limited to two specific areas of the brain, the dentate gyrus of the hippocampus and the subventricular zone (SVZ). Despite continued research investigating neurogenesis in these two regions, we still lack a fundamental understanding of the molecular mechanisms of neural cell division, migration, differentiation, and integration in the postnatal brain. In particular, the rostral migratory stream (RMS), which is a cellular migratory route for newly generated neuronal precursors that travel from the SVZ to the olfactory bulb, will provide a useful model …

Astroglial Boundary Formation And Epha4 Signaling In Neuroblast Migration, Nicholas B. Gallo

Honors Scholar Theses

Adult neurogenesis, the process of generating new neurons from neural precursors, is a highly complex process that is limited to two specific areas of the brain, the dentate gyrus of the hippocampus and the subventricular zone (SVZ). Despite continued research investigating neurogenesis in these two regions, we still lack a fundamental understanding of the molecular mechanisms of neural cell division, migration, differentiation, and integration in the postnatal brain. In particular, the rostral migratory stream (RMS), which is a cellular migratory route for newly generated neuronal precursors that travel from the SVZ to the olfactory bulb, will provide a useful model …

Eeg-Microstate Dependent Emergence Of Perceptual Awareness, Juliane Britz, Laura Díaz Hernàndez, Tony Ro, Christoph M. Michel

Publications and Research

We investigated whether the differences in perceptual awareness for stimuli at the threshold of awareness can arise from different global brain states before stimulus onset indexed by the EEG microstate. We used a metacontrast backward masking paradigm in which subjects had to discriminate between two weak stimuli and obtained measures of accuracy and awareness while their EEG was recorded from 256 channels. Comparing targets that were correctly identified with and without awareness allowed us to contrast differences in awareness while keeping performance constant for identical physical stimuli. Two distinct pre-stimulus scalp potential fields (microstate maps) dissociated correct identification with 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 …

The New Normal: Goodness Judgments Of Non-Invariant Speech, Julia R. Drouin

Honors Scholar Theses

Previous research has found that perceptual learning, or normalizing the idiosyncratic phonemes of speech, causes a shift in speech sound category boundaries. The present study examined if perceptual learning was limited to the boundary or if also caused a shift in internal category structure. Seventeen individuals participated in three behavioral tasks to explicate this question. In the Lexical Decision task, participants were trained in either /s/-biasing or /ʃ/- biasing context. In the Goodness Judgment task, participants rated a continuum of sounds on perceived /s/ goodness using a designated scale. Finally, in the Phoneme Identification task, participants listened to the same …

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 …

Neuromodulation Therapy Mitigates Heart Failure Induced Hippocampal Damage, Timothy P. Diperi

Undergraduate Honors Theses

Cardiovascular disease (CVD) is the leading cause of death in the United States. Nearly half of the people diagnosed with heart failure (HF) die within 5 years of diagnosis. Brain abnormalities secondary to CVD have been observed in many discrete regions, including the hippocampus. Nearly 25% of patients with CVD also have major depressive disorder (MDD), and hippocampal dysfunction is a characteristic of both diseases. In this study, the hippocampus and an area of the hippocampal formation, the dentate gyrus (DG), were studied in a canine model of HF. Using this canine HF model previously, we have determined that myocardial …

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

Renée Crown University Honors Thesis 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 …

Propagation Of Oligomeric Α-Synuclein And Amyloid-Β: Implications For Parkinson's And Alzheimer's Diseases, Matthew Stephen Planchard

Master's Theses

The aggregation of amyloidogenic proteins is a critical event in the pathology of a variety of neurodegenerative diseases, including Alzheimer’s disease (AD) and Parkinson’s disease (PD). The proteins α-synuclein (αS) and amyloid-β (Aβ) are involved in the formation of amyloid lesions observed in PD and AD, respectively. Both PD and AD exhibit a significant amount of co-pathology in clinical settings, and the αS and Aβ proteins have been shown to interact in vitro. Recent experimental consensus has shown oligomeric species to be significant, if not primary, sources of toxicity in these diseases. …