Medical Neurobiology Commons^™

Acute And Chronic Effects Of Neuroinflammation On Hippocampus And Anterior Cingulate Cortex Network Dynamics, Lauren A. Crew

UNLV Theses, Dissertations, Professional Papers, and Capstones

Neuroinflammation has emerged as a critical modulator of cognitive function and neural circuit dynamics, yet the distinct contributions of acute and chronic neuroinflammation to brain function remain poorly defined. This dissertation examines how inflammation independently alters large-scale neural activity and behavior, focusing on interactions between the hippocampus (HPC) and anterior cingulate cortex (ACC), regions essential for memory and executive processes. Using in vivo electrophysiological techniques in a rodent model, this study compares the effects of short-term (acute) and prolonged (chronic) neuroinflammatory states, induced via Poly I:C, on neural oscillations, regional coherence, and spatial coding. Findings reveal that even transient inflammation …

Determining The Effects Of An Hiv Infective Model On The Development Of Neuropathic Pain In Alzheimer’S Disease Model Mice., Ayesha Usman, Megan W. Szobody, Jose Rios, Mohammed Alnoud, Khalid Benamar

Research Colloquium

The purpose of this study is to determine the effect of the Human Immunodeficiency virus (HIV) in producing neuropathic pain in an Alzheimer’s Disease (AD) mouse model. HIV-1 envelope glycoprotein gp120 is correlated with increased release of thermal hyperalgesia and mechanical allodynia mediators from astrocytes and glial cells in rodents, producing the identifiable symptoms of neuropathic pain. Similarly, studies show that 45.8% of AD patients experience chronic pain. The production of an HIV/AD comorbid mouse model will be useful in determining important pathological pathways for neuropathic pain and is vital to future studies in therapeutic approaches to these conditions. Two …

Alteration Of Peripheral Cytokines In Alzheimer’S Disease, Zhengshi Yang

UNLV Theses, Dissertations, Professional Papers, and Capstones

Alzheimer’s disease (AD) is a progressive neurodegenerative disease with the clinical symptoms of gradual cognitive decline and memory loss. Biologically, abnormal accumulation of Aβ (Aβ) plaque and tau tangles in the brain are the core pathological hallmarks in AD. Although inflammatory response is not specific to AD, emerging evidence suggests that the disrupted innate immune system within the central nervous system, particularly microglial activation, might act as the bridge linking Aβ aggregation to pathological phosphorylation and aggregation of tau. The inflammatory response was suggested to initially have a neuroprotective role of attempting to clear Aβ plaques, and then become neurotoxic …

Delineating Genetic Influences On Neurodegenerative Disorders And Infectious Diseases Through Advanced Computational Methods, Xiaowei Zhuang

UNLV Theses, Dissertations, Professional Papers, and Capstones

Genetics plays a critical role in understanding the molecular mechanisms underlying neurodegenerative disorders and pathogen evolution in infectious diseases. For example, identifying genetic variants associated with a disease phenotype uncovers functional pathways that could lead to potential drug targets and therapeutic interventions. In addition, tracking the genetic evolution of pathogens enables early detection and warning of infectious disease outbreaks. In both applications, given the large amount of genetic data, advanced computational methods, including longitudinal and multivariate models, could significantly boost the statistical power and capture interrelationships among traits, environmental factors and genetic influences. This dissertation focuses on four applications of …

Utilizing Ai Integrated Neuroimaging Technology To Expand Upon Machine Learning In Positron Emission Tomography Technology With The Aim Of Detecting Amyloid Beta Biomarkers Early In The Onset Of Alzheimer's., Ethan S. Terman

Undergraduate Research Posters

Early intervention in Alzheimer's is vital for treatment. The earlier a professional can detect symptoms and make a diagnosis the earlier a prognosis can be implemented. With the prevalence of data in our day-to-day world combined with Artificial intelligence (AI), utilizing both for machine learning can pave the way for more accurate and efficient detection of Alzheimer's and other neurodegenerative diseases. AI combined with Machine learning (ML) increases diagnostic efficiency and reduces human errors, making it a valuable resource for physicians and clinicians alike. With the increasing amount of data processing and image interpretation required, the ability to use AI …

The Genetic Relationship Between Peripheral Inflammation And Alzheimer’S Disease, Davis Cammann

UNLV Theses, Dissertations, Professional Papers, and Capstones

Alzheimer’s disease (AD) is the leading cause of dementia worldwide, and has become an ever-present problem in aging populations. An increasing body of evidence suggests that neuroinflammation is one of the key drivers of AD pathology. One overlooked contributor to this burden is peripheral inflammation throughout the body. Due to increased permeability of the blood-brain-barrier (BBB) in older age, inflammatory plasma proteins and immune cells infiltrate the CNS and drive neuroinflammation through interactions with neurons and glia. In addition, age-related changes in the composition of gut microbiome taxa lead to increased gut permeability and inflammatory burden. Because inflammatory factors are …

Infiltrating Cd8+ T Cells Exacerbate Alzheimer’S Disease Pathology In A 3d Human Neuroimmune Axis Model, Jefin Jose, Devam Purohit

VCU's Medical Journal Club: The Work of Future Health Professionals

In this study, Jorfi et al. employed a neuroimmune axis model containing neurons, astrocytes, and microglia to examine the role of immune cells in Alzheimer's disease. Jorfi et al. found that T cells selectively infiltrated the BRAIN compartment of the neuroimmune axis model as compared to B cells and monocytes. Jorfi et al. further found that CD8+ T cells demonstrated heightened cytotoxicity in the Alzheimer's disease brain, illuminating the role of immune cells in neurodegeneration. Upon further examination, the CXCR3-CXCL10 signaling pathway was found to have an important role in inflammation.

Selenomethionine Protects Mutant Tau N27a Cell From Oxidative Stress And Decreases Phosphorylation Of Tau, Madelin Locicero

Celebration of Learning

Alzheimer’s Disease (AD) is neurodegenerative disease characterized by loss of cells and aggregated tau in the hippocampus. Hyperphosphorylated tau causes the misfolding of tau proteins (aggregated tau), which are responsible for proper neuronal activity. Selenium-methionine has been known to decrease the amount of phosphorylated tau within mutant and wild type 3xTg- AD mice. However, selenium can be toxic to cell depending on the type of cells and the concentration of selenium. The purpose of this study is to determine the effect selenium-methionine has on decreasing hyperphosphorylation of tau, protecting cells from oxidative stress, and decreasing the amount of aggregated tau …

An Evaluation Of Alzheimer's Disease-Related Pathology In Two Different Models Of Diabetes In Immune-Challenged Mice, Andrew Scott Murtishaw

UNLV Theses, Dissertations, Professional Papers, and Capstones

Obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome are related disorders with wide-ranging and devastating effects that can be observed throughout the body. One important and understudied organ of damage is the brain. Clinical and epidemiological studies have found that T2DM, and more specifically hyperinsulinemia, significantly increases the risk of cognitive decline and increases the likelihood of Alzheimer’s disease (AD) and other forms of dementia in the elderly. Insulin has slightly different functions in the peripheral body than in the central nervous system and the dysregulation of these functions may contribute to the onset and progression of late-life neurodegenerative …

Enhanced Cgmp-Dependent Signaling In Astrocytes: Novel Therapeutic Target In Alzheimer's Disease, Nyema M. Woart

PCOM Biomedical Studies Student Scholarship

Over five million Americans suffer from Alzheimer’s Disease (AD), with an expected 34% increase in the incidence in this disease over the next decade. Unfortunately, there is no cure for AD. Recent studies have indicated that drugs which increase the levels of cyclic guanosine-3’5’-monophosphate (cGMP) may help preserve learning and memory in AD and enhance cognition in the aging brain; however, the mechanism(s) of how cGMP exerts this beneficial effect is unknown. The present findings now suggest that elevation of cGMP in astrocytes depresses inhibitory potassium currents in these cells to stimulate their protective influence on neuronal activity. Cellular currents …

Analysis Of Differential Mrna And Mirna Expression In An Alzheimer’S Disease Mouse Model, Amanda Hazy, Matthew Dalton

Other Undergraduate Scholarship

Research has shown that changes in gene expression play a critical role in the development of Alzheimer’s Disease (AD). Our project will evaluate genome-wide RNA expression patterns from brain and blood in an AD mouse model. This analysis will provide insight regarding the mechanisms of AD pathology as well as determine a possible diagnostic tool utilizing RNA expression patterns found in the blood as biomarkers for AD.

Deficiency In P38Β Mapk Fails To Inhibit Cytokine Production Or Protect Neurons Against Inflammatory Insult In In Vitro And In Vivo Mouse Models, Bin Xing, Adam D. Bachstetter, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

The p38 MAPK pathway plays a key role in regulating the production of proinflammatory cytokines, such as TNFα and IL-1β, in peripheral inflammatory disorders. There are four major isoforms of p38 MAPK (p38α, β, δ, γ), with p38α and p38β the targets of most p38 MAPK inhibitor drugs. Our previous studies demonstrated that the p38α MAPK isoform is an important contributor to stressor-induced proinflammatory cytokine up-regulation and neurotoxicity in the brain. However, the potential role of the p38β MAPK isoform in CNS proinflammatory cytokine overproduction and neurotoxicity is poorly understood. In the current studies, we used primary microglia from wild …

Characterization Of Amino Acid Residues Integral To Neuronal Binding Of Amyloid Beta Protein In Alzheimer’S Disease, Nicole C. Olson

Chemistry and Biochemistry

Purpose:  Alzheimer’s Disease is a neurodegenerative disease resulting from over-production and neuronal accumulation of amyloid-beta proteins (Aβ40/Aβ42). The glycine residue at position 33 and histidine residues at positions 13 and 14 are involved with binding and internalization of these proteins, actions potentially inhibited by substituting or sterically hindering these residues with an antibody specific to positions 2-11 (IgG-4.1). Rat pheochromocytoma (PC12) cells differentiated with nerve growth factor were used as a neuronal model to determine whether substitution and/or antibody block amyloid-beta’s neuronal interactions.

Methods:  PC12 cells were incubated with fluorescein-labeled-amyloid-beta-40 (F-Aβ40) or substituted F-Aβ40 derivatives (F-Aβ40-H13,14G, F-Aβ40-H13,14G;G33A), with or without …