Neuroscience and Neurobiology Commons^™

Cytotoxic Analysis Of Old Drugs: New Drugs For Alzheimer’S Disease, Sebastian Yumiseba

Theses and Dissertations

Microglia are the resident immune cells of the CNS and constitute about 10% of all cells in the CNS. They have a vital role in Alzheimer’s pathogenesis as either cytotoxic or neuroprotective. Recent efforts are being put into repurposing drugs to target the microglia to treat Alzheimer’s disease.

Characterization Of And Cellular Mechanisms Underlying Spinal Non-Viral Interleukin-10 Gene Therapy Formulated With D-Mannose For Treatment Of Peripheral Neuropathic Pain, Arden Grace Vanderwall

Biomedical Sciences ETDs

Anti-inflammatory intrathecal non-viral interleukin-10 (IL-10) gene therapy provides enduring relief of chronic pain in numerous animal pain models. Co-administration of the mannose receptor (MR) ligand D-mannose (DM) improves non-viral IL-10 gene therapeutic efficacy, but questions remain regarding which pain-relevant tissues are critical for non-viral transgene expression resulting in long-lasting pain relief. Additionally, the role of endogenous IL-10 in non-viral IL-10 therapeutic effects is completely unknown.

Chapter I is an Introduction to the studies detailed in this dissertation, providing a historical perspective of the field of neuroinflammation and a framework upon which neuroimmune processes intersect with mechanisms underlying pathological pain. The …

Translating Touches: New Approaches For Modeling And Rescuing Executive Function Deficits After Prenatal Alcohol Exposure, Johnny A. Kenton

Biomedical Sciences ETDs

Background: With a recent meta-analysis indicating that 9.8% of women worldwide consume alcohol during pregnancy, understanding the effects of fetal alcohol spectrum disorder (FASD) is critical for both identifying and treating those afflicted. Traditional preclinical research investigating the behavioral effects of neurodevelopmental disorders, such as FASD, has utilized tasks designed for specific animal models. For this reason, preclinical research into FASD requires a shift into clinically relevant behavioral testing. One such method involves touch-sensitive screens integrated into an operant box to emulate clinical computer-based tasks, such as the Cambridge Neuropsychological Test Automated Battery.

Methods: Here, we utilized a mouse model …

Using Machine Learning To Conduct A Detailed Behavioral Analysis In An Appetitive Social Learning Task, Thomas Shao

Honors Scholar Theses

Learning by watching others, or observational learning, is important for social development and survival. However, not much is known about the brain mechanisms underlying this type of learning. Since the 1960s, observational learning has been widely studied in humans, but developing and analyzing experiments for animals has been challenging. Here, I explore observational learning using a novel paradigm while performing an analysis that involves tracking the rats using an active learning paradigm called DeepLabCut. In this novel paradigm, customized operant conditioning chambers are used for the rats to observe and learn from another animal repeatedly on multiple trials each day. …

Expression Analyses Of Hippocampal And Cortical Proteins In A Rat Model For Alzheimer’S Disease, Rangon Islam

Theses and Dissertations

Currently, Alzheimer’s disease (AD) has no cure. Using a rat AD model, we identified aberrantly expressed proteins during pre-pathology as potential biomarkers. The expression of certain biomarkers was reversed by diazoxide, a repurposed hypertension drug. These results suggest that drug repurposing at an early stage of AD has therapeutic potential.

Hiv-1 Tat Interactions With Opioids Are Modulated By Progesterone And Estradiol, Dejun Jackson

Honors Theses

HIV infection and combined substance abuse are comorbid epidemics. Previous studies show that concurrent opioid drug use may potentiate HIV-1-mediated neurotoxicity partly via interactions with opioids. Preclinical studies suggest that the HIV-1 trans-activator of transcription (Tat), an HIV regulatory protein, can synergize with opioids to exacerbate its already neurotoxic effects. However, its interactions with clinical opioids, such as oxycodone, have yet to be elucidated. Additionally, Tat disrupts a number of systems including the dopaminergic system, which contribute to its capacity to potentiate the rewarding effects of abused drugs. Although the neurotoxic effects of Tat may be inhibited by gonadal steroids …

Remapping Of Place Cells In The Dorsal And Ventral Hippocampus In Response To Environmental Change, Aditi Anam

Honors Scholar Theses

The hippocampus is an important brain structure involved in memory and navigation of both rats and humans. Neurons in the hippocampus can be “spatially” tuned, meaning they fire in specific physical locations. These spatially tuned cells are referred to as place cells. Collectively, they are thought to provide a map-like representation of the environment around us. If the environment is changed, some place cells can adjust by “remapping”, or altering their firing patterns. There are multiple sub-regions within the hippocampus. During experiments, cells were recorded simultaneously from the dorsal and ventral hippocampus of rats running on a track for food …

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 …

Sexually Dimorphic Alterations In Brain Morphology Of Astrocyte Conditional System Xc- Knockout Mice, Gabrielle Emily Samulewicz

Renée Crown University Honors Thesis Projects - All

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 Insulin-Like Growth Factor-1 (Igf-1) And Insulin-Like Growth Factor Receptor (Igfr) Regulation On Cognition And Structure Of Astrocytes, Sariya Khan

Honors Theses

Insulin-like growth factor-1 (IGF-1) is a neuroendocrine signaling hormone that plays an integral role in bone and tissue growth and development. Inhibition of this hormone is known to disrupt the chemistry of the brain, resulting in cognitive impairments such as those seen in many common neurodegenerative diseases. While much research has been conducted on neurons and their relation with IGF-1, the role of astrocytes still needs to be explored. Our research investigates how astrocytes are affected as a result of IGF-1 regulation. Preliminary studies in our laboratory established a connection between IGF-1 and glial fibrillary acidic protein (GFAP), and in …

The Raphe-Hippocampal Tract And Its Age Differences: Diffusion Tensor Imaging And Probabilistic Tractography Study, Ashley Sekul

Honors Theses

The raphe-hippocampal tract links the raphe nuclei to the hippocampus and is responsible for the production of the neurotransmitter serotonin. The hippocampus is key in regulating emotional and stress responses. This study utilized diffusion tensor imaging which uses Functional Magnetic Resonance Imaging to provide scans of the brain for analyzing differences in the raphe-hippocampal tract as one ages. In this specific study, 491 samples were visually analyzed to gather data about the fractional anisotropy of the raphe nuclei in both male and female brains ranging from 6 to 85 years old. Through the ranking of images, some were discarded, and …

Effects Of Repeated Intermittent Episodes Of Social Stress On The Acquisition And Extinction Of A Reward-Seeking Task, Nikki Sullivan

Honors Theses

Repeated exposure to stress is known to have a myriad of effects on the brain, contributing to the development of psychiatric disorders, such as anxiety, depression, and drug addiction. For example, rats undergoing repeated social stress develop increased cocaine self-administration. These effects of stress are not well-understood and are related to changes in the brain reward system. This study investigated the effects of repeated social stress on reward-seeking behavior via the acquisition and extinction of a discriminative stimulus (DS) task and on anxiety-like behavior in the elevated plus maze (EPM). Male rats underwent intermittent social defeat (4 sessions in 10 …

Dynamic Oscillatory Interactions Between Neural Attention And Sensorimotor Systems, Alex Wiesman

Theses & Dissertations

The adaptive and flexible ability of the human brain to preference the processing of salient environmental features in the visual space is essential to normative cognitive function, and various neurologically afflicted patient groups report negative impacts on visual attention. While the brain-bases of human attentional processing have begun to be unraveled, very little is known regarding the interactions between attention systems and systems supporting sensory and motor processing. This is essential, as these interactions are dynamic; evolving rapidly in time and across a wide range of functionally defined rhythmic frequencies. Using magnetoencephalography (MEG) and a range of novel cognitive paradigms …

Molecular And Behavioral Studies In Cdkl5 Deficiency Disorder, Ethan Schroeder

Theses & Dissertations

CDKL5 Deficiency Disorder (CDD) is an X-linked neurodevelopmental disorder associated with epilepsy, developmental retardation, autism, and related phenotypes. Currently, there is no cure available for the disorder. Thus, the identification of cellular and molecular aberrations in this disorder and the generation and validation of mouse models that recapitulate core aspects of the disorder are a pressing need in the field. Our studies are aimed at filling this gap.

Mutations in the CDKL5 gene, encoding CDKL5, have been identified in this disorder. CDKL5 is a protein with homology to the serine-threonine kinases and incompletely characterized function. Mutations in CDKL5 are predominately …

Flavonoid And Cannabidiol Neural Glyoxalase Pathway Enhancement Against Aging And Alzheimer’S Disease, Joel R. Frandsen

Theses & Dissertations

Alzheimer’s Disease is a neurodegenerative condition featuring neural cell death and a decline in cognitive capacity caused by elevated inflammation and production of reactive oxygen species. The glyoxalase pathway is an endogenous antioxidant system that neutralizes reactive methylglyoxal through sequential reactions. Dysfunction of the glyoxalase pathway contributes to oxidative stress and the accumulation of inflammatory metabolic byproducts. Plant-produced compounds with antioxidant activity can enhance endogenous antioxidant pathways and protect cells from elevated ROS production. We hypothesize that flavonoids and limited Cannabis Sativa-produced cannabidiol can enhance glyoxalase pathway function through regulation of antioxidant and pro-apoptotic signaling pathways to prevent methylglyoxal-mediated …

Effect Of Ambient Temperature On Recovery Of Surgically Instrumented Sprague-Dawley Rats, Gianna Mangone

Senior Honors Projects, 2020-current

Based on current guidelines for housing rodents after surgical instrumentation, rodents may be housed at temperatures that hinder surgical recovery and cause thermal stress– room temperature (21°C) being one of them. Rodents are often housed at room temperature since this temperature is easy for humans to be caring for them. However, if recovering rodents are thermally stressed, experimental results will be confounded. To address this issue, Sprague-Dawley rats were surgically instrumented with radiotelemtry thermoprobes (Data Sciences, #TA-10F40) to monitor their core temperatures, then housed at one of five temperatures to assess the effect ambient temperature had on multiple aspects of …

Dependence Of The Nociceptive Withdrawal Response On Stimulus Location In The Intact, Unanesthetized Rat, Brady Simpson

Senior Honors Projects, 2020-current

The nociceptive withdrawal response (NWR) is a critical movement characterized by the avoidance of noxious or otherwise unwanted stimuli. The response is mediated in mammals by withdrawal of the hind limb. Although the NWR has been studied in humans and spinalized animals, it is unclear whether there is a dependence on stimulus location in intact, unanesthetized, non-human animals. The specific aim of my research was to use high speed video of the intact, unanesthetized rat’s limb to determine if there was an effect of stimulus location on hind limb movement during the NWR evoked by heat stimuli. I hypothesized, based …

Do Innexins Function In The Extreme Cold Response Of Drosophila Melanogaster, Madison A. Ward

Masters Theses, 2020-current

Nociception is an organism’s ability to detect, process and reflexively respond to potentially damaging stimuli. While the process of nociception has clear, protective advantages, inappropriate and prolonged signaling can lead to chronic pain in humans. Nociception is a vital and genetically conserved process, thus cold nociception in Drosophilaprovides a model for identifying molecular components required for nociceptor function in vertebrates. Drosophila Class III dendritic arborization (da) neurons have previously been shown to be involved in the cold nociceptive response. Due to the importance of fast response to damaging stimuli, we hypothesize that electrical synapses are involved in cold nociception. …

The Current Neuroscientific Understanding Of Alzheimer's Disease, Rachel A. Brandes

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

Alzheimer’s disease is a degenerative neurological illness characterized by the deterioration of brain regions implicated in memory and cognitive function. While researchers have yet to find a cure or effective treatment, they have gained a better understanding of its pathology and development. Through years of neuroscience research, scientists have discovered much of what happens in the brain during Alzheimer’s disease onset and how this causes its symptoms; many hypotheses regarding this aspect of the illness involve temporal lobe atrophy, neurofibrillary tangles, and amyloid plaques. Although Alzheimer’s disease affects millions of people every day, it seems that most are unaware of …

Working Memory And Attention Deficits During A Letter Number Sequencing Task Post-Concussion, Shannon Kiss

Neuroscience Honors Papers

As the prevalence of sports related concussions rise, the long-term effects of concussions have garnered increasing research attention. Previous research has demonstrated that certain dimensions of executive function are especially susceptible to mild traumatic brain injury (mTBI), specifically working memory and attention. Previous studies using EEG have found that increased very low frequency oscillations (VLFO) disrupt goal-oriented activities and are associated with difficulties in cognition, hyperactivity and inattention in concussed individuals after mTBI. This study utilized continuous EEG during a letter number sequencing task on concussed and non-concussed individuals to assess deficits related to working memory and attention. It was …

Neurocognitive Risk Factors And Current Intervention Strategies For Survivors Of Pediatric Acute Lymphoblastic Leukemia, Abigail Taber

Senior Honors Theses

The improved survival rate for pediatric cancer patients is one of the greatest triumphs of recent medicine, but the late effects faced by these survivors have been uncovered through this new population of survivors. Many survivors of pediatric acute lymphoblastic leukemia (ALL) experience cognitive deficits in areas such as attention, memory, processing speed, and academic achievement following cancer treatment. Recent research has pointed to chemotherapeutic agents, host risk factors, and genetic predispositions as perpetrators of these deficits, although other factors are also under investigation. Consequently, the search for appropriate interventions for the amelioration of these deficits has dominated the literature …

Detection Of Tinnitus In Cba/Caj Mice Using The Active Avoidance Shuttle Box Test, Grace Nichols

University Scholar Projects

Tinnitus is a neurological condition that involves the perception of a sound that is not actually there. Individuals affected with tinnitus describe the condition as a ringing, buzzing, or whooshing sound in their ears. One-third of the population is estimated to have tinnitus, and for many individuals, the condition negatively impacts quality of life. Difficulty falling asleep, trouble with hearing and concentrating, and in some cases, depression, have all been observed to occur with tinnitus.

Tinnitus has been extensively studied in animals, and behavioral tests are the primary method of evaluating the presence of tinnitus in animals. This study evaluates …

Deficiency Of Complement Component C1q Prevents Cerebrovascular Damage And White Matter Loss In A Mouse Model Of Chronic Obesity., Leah C Graham, Heidi E Kocalis, Ileana Soto Reyes, Gareth R Howell

College of Science & Mathematics Departmental Research

Age-related cognitive decline and many dementias involve complex interactions of both genetic and environmental risk factors. Recent evidence has demonstrated a strong association of obesity with the development of dementia. Furthermore, white matter damage is found in obese subjects and mouse models of obesity. Here, we found that components of the complement cascade, including complement component 1qa (C1QA) and C3 are increased in the brain of Western diet (WD)-fed obese mice, particularly in white matter regions. To functionally test the role of the complement cascade in obesity-induced brain pathology, female and male mice deficient in C1QA, an essential molecule in …

Language, Motor, And Cognitive Outcomes Of Toddlers Who Were Born Preterm, Diane Frome Loeb, Caitlin M. Imgrund, Jaehoon Lee, Steven Barlow

Center for Brain, Biology, and Behavior: Faculty Publications

Purpose: The purpose of this study was to examine the language, motor, and cognitive abilities of children born preterm in four categories: (a) healthy preterm infants, (b) infants of diabetic mothers, (c) infants with respiratory distress syndrome, and (d) infants with chronic lung disease when the children were 30 months, uncorrected age. Comorbidity of language, motor, and cognitive skills was examined, along with predictor variables.

Method: A total of 148 children who were born preterm participated and were assessed using bivariate tests and logistic regression on standardized assessment scores.

Results: Controlling for the children’s gestational age (GA), overall language ability …

Reorganization Of The Human Ventricular-Subventricular Zone Neural Stem Cell Niche In Fetal-Onset Hydrocephalus, Saurabh Kumar

University Scholar Projects

Fetal-onset hydrocephalus is a relatively common birth defect occurring in 1-2 cases per thousand births and is characterized by abnormally expanded brain ventricles. Current diagnosis for this complex pathology often involves relatively simple metrics and heavy reliance on clinician experience over objective measures. Those affected often suffer chronic headaches and cognitive deficits and may present with a bulging skill. Shunting is considered the standard treatment for communicating hydrocephalus (i.e. cerebrospinal fluid flow is physically unobstructed in the ventricular system). Shunting remains a highly invasive procedure often performed during the critical period of infancy and has a high failure rate of …

Levels Of Parp1-Immunoreactivity In The Human Brain In Major Depressive Disorder, Aamir Shaikh

Undergraduate Honors Theses

MDD is a severe and debilitating disorder that is associated with a growing global economic burden due to reduced workplace productivity along with increased healthcare resource utilization. Furthermore, depression markedly enhances the risk for suicide, mortality that is especially worrisome given that 30% of depressed individuals have an inadequate response to current antidepressants. This inadequacy of antidepressants necessitates the discovery of a better understanding of the pathobiology of MDD. Most current antidepressants work through monoamine neurotransmitters, and their relative efficacy in depression led to the now dated monoamine-deficiency hypothesis. The limited usefulness of antidepressants has led to a reinvigorated search …

Effects Of Non-Photic Zeitgebers On The Circadian Clock In The Common House Spider, Parasteatoda Tepidariorum (Araneae: Theridiidae), Mattea Garmany, Darrell Moore, Thomas C. Jones

Undergraduate Honors Theses

Circadian rhythms are endogenous cycles that control physiological and behavioral changes that can be affected by environmental factors which allow most eukaryotic organisms to synchronize their daily activities with the 24-hour day. Parasteatoda tepidariorum,the common house spider, demonstrates a short-period circadian clock averaging 21.6 hours when left in constant darkness, yet they are able to entrain to a 24-hour light cycle. We tested whether these spiders were able to use non-photic Zeitgebers to entrain to the 24-hour day. Periodic presentation of food and disturbance were not found to be effective cues for the spiders’ entrainment. A few individuals were clearly …

Detection Of Tinnitus In Cba/Caj Mice Using The Active Avoidance Shuttle Box Test, Grace Nichols

Honors Scholar Theses

Tinnitus is a neurological condition that involves the perception of a sound that is not actually there. Individuals affected with tinnitus describe the condition as a ringing, buzzing, or whooshing sound in their ears. One-third of the population is estimated to have tinnitus, and for many individuals, the condition negatively impacts quality of life. Difficulty falling asleep, trouble with hearing and concentrating, and in some cases, depression, have all been observed to occur with tinnitus.

Tinnitus has been extensively studied in animals, and behavioral tests are the primary method of evaluating the presence of tinnitus in animals. This study evaluates …

Amygdala And Neocortical Structural Volume Analysis In The Shank3b Mutant Mouse Model Of Autism Spectrum Disorder, Preet Sawhney

Honors Scholar Theses

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that is characterized by abnormal social behavior, deficits in communication, and motor stereotypy. The SHANK3 gene, responsible for the generation of a scaffolding protein that is integral for the development of synapses, has been identified as one of the primary candidate genes implicated in the disorder. Shank3B is the rodent homolog for this gene. Research has shown that when this gene is disrupted in rodent models (e.g., via knock-out (KO)), ASD-like behaviors result. These include deficits in social interaction, increased anxiety, and repetitive self-grooming. The current study aimed to identify a physiological …

Safe Sleep: Developmental Implications For Hospitalized Infants, Katherine Kohlsaat

Senior Honors Projects

The rate at which an infant develops both physically and cognitively is significant during sleep, as this is the time when the entire body can dedicate its efforts to this cause. Parents of healthy infants follow the guidelines set by the American Academy of Pediatrics (AAP) relating to safe sleep, and since their introduction in 1992, the rate of Sudden Infant Death Syndrome (SIDS) has decreased by 40% (Center for Disease Control and Prevention, 2016). However, if an infant has been hospitalized since birth due to necessary invasive procedures such as open-heart surgery, these protocols cannot be initially implemented. Common …