Life Sciences Commons^™

Theta Burst Brain Stimulation In Painful Diabetic Neuropathy Patients: Investigating Neural Mechanisms, Bhushan Thakkar

Theses and Dissertations

Chronic pain (CP) is a significant contributor to disability and disease burden globally. In 2019, approximately 50.2 million adults (20.4% of the US population) experienced chronic pain, contributing to $560-635 billion in direct medical costs. In addition, the worldwide prevalence of diabetes mellitus has reached epidemic proportions and is set to increase to 629 million by 2045. Almost 50% of patients with diabetes present with diabetic neuropathy (DN), and one in five patients with diabetes presents with painful DN (pDN) which is the most common cause of neuropathic pain (NP) in the US. Symptomatic treatment is the mainstay of management …

Contextually Modulated Avoidance Behavior In Rats Post-Pavlovian Extinction, Lauren Branigan

Theses and Dissertations

The following study sought to examine the psychological substrates of renewal (e.g.., context dependent extinction processes) for conditioned avoidance behaviors in rats. Using signaled active avoidance conditioning, rats acquired two-way shuttle responding, to two different auditory stimuli. These behaviors were then extinguished through exposure to the auditory stimuli where shuttling behavior was now without consequence. Subjects were then tested for renewal of avoidance in three distinct renewal sequences (e.g., ABA vs ABB, AAB vs AAA, and ABC vs ABB) in three separate groups of rats. It was found that subjects showed more responding to a stimulus presented outside of its …

Enhanced Proteomics Resolves Kcc2 As A Novel Therapeutic Target For Traumatic Brain Injury, Pavel N. Lizhnyak

Theses and Dissertations

The development of traumatic brain injury (TBI) therapeutics and effective translation to clinic remains stubbornly elusive despite the high prevalence of TBI within the United States and across the globe. Interventions must be devised around testable targets, appropriately timed to intercede on secondary results. Here, we have utilized temporal neuroproteomics as an ideal approach to inform on the complex biochemical processing in order to address the well-recognized temporal evolution of TBI pathobiology and interrogate a novel therapeutic target in a mild-moderate rat Controlled Cortical Impact (CCI) within perilesioned somatosensory cortex. First, our findings revealed 2047 proteins significantly impacted within the …

The Effects Of The Hiv-1 Tat Protein And Morphine On The Structure And Function Of The Hippocampal Ca1 Subfield, William D. Marks

Theses and Dissertations

HIV is capable of causing a set of neurological diseases collectively termed the HIV Associated Neurocognitive Disorders (HAND). Worsening pathology is observed in HIV+ individuals who use opioid drugs. Memory problems are often observed in HAND, implicating HIV pathology in the hippocampus, and are also known to be exacerbated by morphine use. HIV-1 Tat was demonstrated to reduce spatial memory performance in multiple tasks, and individual subsets of CA1 interneurons were found to be selectively vulnerable to the effects of Tat, notably nNOS+/NPY- interneurons of the pyramidal layer and stratum radiatum, PV+ neurons of the pyramidal layer, and SST+ neurons …

Protein Kinase M Zeta-Mediated Ltp Maintenance In The Non-Human Primate Hippocampus: A Role For Stress And Serotonergic Signaling In Affective Processing, Sasha L. Fulton

Theses and Dissertations

Early-Life Stress (ELS) is associated with vulnerability to mood disorder, but it’s not well understood how ELS contributes to deficits in cognitive function. Atypical PKMzeta is critical for LTP maintenance and memory. The current study aims to characterize the ELS phenotype with respect to this key marker of hippocampal LTP.

A Systems Biology Approach To Detect Eqtls Associated With Mirna And Mrna Co-Expression Networks In The Nucleus Accumbens Of Chronic Alcoholic Patients, Mohammed Mamdani

Theses and Dissertations

Alcohol Dependence (AD) is a chronic substance use disorder with moderate heritability (60%). Linkage and genome-wide association studies (GWAS) have implicated a number of loci; however, the molecular mechanisms underlying AD are unclear. Advances in systems biology allow genome-wide expression data to be integrated with genetic data to detect expression quantitative trait loci (eQTL), polymorphisms that regulate gene expression levels, influence phenotypes and are significantly enriched among validated genetic signals for many commonly studied traits including AD.

We integrated genome-wide mRNA and miRNA expression data with genotypic data from the nucleus accumbens (NAc), a major addiction-related brain region, of 36 …