Neurosciences Commons^™

Molecular Mechanisms Of Opioid Use Disorder In Human Brain Models, Emily Mendez

Dissertations & Theses (Open Access)

Opioid use disorder (OUD) is a national and global public health crisis with no end in sight. While studies from animal models hint at widespread epigenetic and transcriptomic alterations of opioid drugs, the molecular consequences of long-term exposure to opioid drugs in human brain is still unclear, and human-centered translational models are necessary to discern the human cell type-specific effects of OUD.

Using postmortem brain Brodmann area 9 (BA9) from the UTHealth Brain Collection for Research on Psychiatric Disorders, I identified angiogenic gene networks perturbed in the RNA and protein of OUD subjects, as well as downregulation of many neuron-correlated …

Exploring Neuroplasticity Changes In Neurotoxin-Induced Parkinson’S Disease: A Preliminary Analysis Using Transcranial Magnetic Stimulation, Tomas Gomez Jr., Daniel Salinas, Kelsey Potter-Baker, Nawaz Hack, Ramu Vadukapuram

Research Symposium

Background: Parkinson’s disease (PD) is a neurodegenerative condition that affects movement, cognition, gait, and significantly impacts one's quality of life. Studies have suggested that neurotoxin pre-exposure is related to PD pathology and progressive motor/non-motor deficits, though it remains unclear how neurotoxin exposure affects neuroplasticity. The present study aimed to examine neurotoxin–induced PD-associated neuroplasticity changes in relationship to mental acuity and PD motor functionalities.

Methods: 7 voluntary participants experiencing early-stage PD symptoms with self-reported neurotoxin pre-exposure were enrolled in the longitudinal, repeated-measures clinical study; 2 sex-matched, age-matched, and occupation-matched healthy subjects were recruited for controlled comparative analysis (n=9). UTRGV’s Institute …

Gamma-Aminobutyric Acid (Gaba) Neurons And Perineuronal Nets (Pnn) In The Monodelphis Domestica And Relevance To Psychiatric Disorders, Jatziry Z. Luna Escobedo, Mariela Garcia, John L. Vandeberg, Mario Gil

Research Symposium

Background/ Purpose: Gamma-aminobutyric acid (GABA) is an amino acid that serves as the central nervous system’s (CNS) main inhibitory neurotransmitter. By inhibiting nerve transmission, it works to lower neuronal excitability. Altered GABA levels have been associated with a variety of psychiatric disorders, for example Epilepsies, Parkinson’s Disease, and Schizophrenia. Perineuronal nets (PNN) are extracellular molecules that are released by neurons and glial cells that modulate many neuronal and glial functions by encapsulating the inhibitory cells and neurites. Altered PNN levels serve as a potential trigger to synaptic imbalance. The purpose of this study is to quantify and analyze the presence, …

Contribution Of 24-H Blood Pressure Variability To Dementia-Related Disorders In Hispanics, Nura Salhadar, Kristina Vatcheva, Silvia Mejia-Arango, Luis J. Mena, Ney Alliey-Rodriguez, Carlos A. Chavez, Ciro A. Goana, Egle Silva, Gustavo Calmon, Rosa P. Mavarez, Joseph H. Lee, Joseph D. Terwilliger, Jesus D. Melgarejo, Gladys E. Maestre

Research Symposium

Introduction: As the number of people living with dementia is increasing at alarming rates worldwide, there is an urgent need to understand the physiopathology of dementia syndromes. Among the most important preventable risk factors, treatment of vascular risk factors such as high blood pressure (BP) decreases the risk of Alzheimer’s disease and related dementias (ADRD). Recent evidence suggests that examining BP variability provides additional physiopathological and predictive information above the mean BP level. However, studies examining the relationship between 24-h BP variability and ADRD are limited, and evidence of the association with dementia has not been documented yet. Therefore, we …

Characterization Of Anti-Cancer Properties Of Fungal Metabolite Ophiobolin A, Asma Syed, Rozena Shirvani, Maximiliano Arath Morales, Shizue Mito, Alexander Kornienko, Xiaoqian Fang

Research Symposium

Background: Ophiobolin A (Oph A) is a secondary metabolite and a phytotoxin produced by the pathogenic fungi Cochliobolus heterostrophus that causes “southern corn leaf blight” disease in maize via modulation of the calcium binding protein calmodulin. Numerous studies have found antiproliferative effects of Ophiobolin A against a variety of cells including bacteria and various cancers including melanoma, glioma and leukemia. Recent studies have shown that OphA induces paraptosis-like cell death in glioblastoma multiforme (GBM) cells via vacuolization of the cytoplasm and enlargement of the mitochondria and endoplasmic reticulum. Notably, unlike apoptosis, paraptosis cell death lacks DNA fragmentation and activation …

Selective Targeting Of Microglia By Quantum Dots And Green Synthesis Of Metal Organic Biohybrids; Applications In Dynamic Cell And Assay Systems, Navya Uppu

Doctoral Dissertations

Neurological disorders are the leading cause of physical and cognitive disability across the globe, currently affecting approximately 15% of the worldwide population. Part of the glioma microenvironment are microglia, resident immune cells of the CNS that were thought to be involved in the pathogenesis of diverse neurodegenerative diseases. Though it remains uncertain what triggers microglial activation in these disorders, targeting and tracking microglial functions using nanotools like Quantum Dots (QDs) could help us elucidate them in such neurological diseases. This research focuses on the comparative study of different QDs formulations and their selective uptake by brain microglia in primary cultures …

Neural Correlates Of Fear Extinction: Investing The Impact Of Puberty And Sex In Children And Adolescents Through Neuroimaging, Sneha Bhargava, Clara Zundel, Samantha Ely, Carmen Carpenter, Reem Tamimi, Leah Gowatch, Mackenna Shampine, Emilie-Clare O'Mara, Jovan Jande, Shravya Chanamolu, Ahmad Almaat, Hilary Marusak

Medical Student Research Symposium

Fear-based disorders, including anxiety and posttraumatic stress disorder, are more prevalent in females than males. Steroid hormones (e.g., estradiol) are involved in fear extinction learning and later recall—a process implicated in the pathophysiology of fear-based disorders. Fear-based disorders commonly emerge during the transition from childhood to adolescence, a period marked by the onset of puberty and a natural increase of steroid hormones. Here, we examined the effects of puberty, sex, and their interaction on extinction recall and underlying neural circuitry in youth. Eighty-five youth (6-17 years, 46% female) completed a two-day Pavlovian fear extinction paradigm while undergoing functional magnetic resonance …

Epithelial And Mesenchymal Olfactory Stem Cells Gathered With Minimally-Invasive Micro-Brush, Tyler Petersen

Medical Student Research Symposium

Spinal cord injury (SCI) causes devastating lifestyle and financial consequences for the patient. Treatment strategies emphasize neuroprotection, but not regeneration. In this regard, stem cells are an innovative field of study that has the potential to regenerate neural tissue, thereby increasing a person’s ability to regain function. The purpose of this project is two-fold: to attain olfactory stem cells located in the nasal canal in a minimally-invasive way and to gather neural cells from the epithelium and mesenchymal cells in the lamina propria. Cells were gathered with sterile nasal micro-brushes, stored, and grown in flasks. After cells reached confluency, they …

The Role Of Diet And Gut Microbiota In Alzheimer’S Disease, D. M.Sithara Dissanayaka, Vijay Jayasena, Stephanie R. Rainey-Smith, Ralph N. Martins, W. M.A.D.Binosha Fernando

Research outputs 2022 to 2026

Alzheimer’s disease (AD), the most prevalent form of dementia, is characterized by the accumulation of amyloid-beta (A ) plaques and hyperphosphorylated tau tangles. Currently, Alzheimer’s disease (AD) impacts 50 million individuals, with projections anticipating an increase to 152 million by the year 2050. Despite the increasing global prevalence of AD, its underlying pathology remains poorly understood, posing challenges for early diagnosis and treatment. Recent research suggests a link between gut dysbiosis and the aggregation of A , the development of tau proteins, and the occurrence of neuroinflammation and oxidative stress are associated with AD. However, investigations into the gut–brain axis …

High-Grade Avm. Educational Vignette And Clinical Cases, Marcos Devanir Silva Da Costa, Marcelo Augusto Acosta Goiri, Daniela Coelho, Juan Alberto Paz Archila, Talita Helena Martins Sarti, Feres Chaddad-Neto

Archives of Neurosurgery

The arteriovenous malformation (AVM) is a vascular malformation characterized by fistulas between arteries and veins forming a nidus, without interposition of capillary vessels and of which early draining vein is identified at the digital angiography. Potential reports of its existence date from the second century AD. Spetzler and Martin (S-M) proposed a classification considering three features and Lawton then added new predictors. A maximum of 10 score can be achieved by applying the modified S-M grade system. This classification guides decision-making and the possible choice of the multimodal treatment (surgery, radiosurgery and embolization). We discuss historical, pathological, clinical and therapeutic …

Validation Of A Virtual Auditory Space, And Its Use To Investigate How Pitch And Spatial Cues Contribute To Perceptual Segregation Of Auditory Streams, Nima Zargarnezhad

Electronic Thesis and Dissertation Repository

The human auditory system can decompose complex sound mixtures into distinct perceptual auditory objects through a process (or processes) known as Auditory Scene Analysis. Pitch and spatial cues are among the sound attributes known to influence sequential streaming (Plack 2018). In this project, the fidelity of a virtual acoustic space (the Audio Dome) in reproducing precisely located sound sources with a 9^th-order ambisonics algorithm was validated. The estimated horizontal Minimum Audible Angles aligned with previously reported values (Mills 1958) homogeneously across the space, and a robust low-frequency presentation was identified. Then, the Audio Dome was utilized to test …

Brain-Derived Neurotrophic Factor (Bdnf) Signaling Mechanisms That Regulate Learning And Memory In Rats, Clementine Faye Harvey

Theses - ALL

Brain-derived neurotrophic factor (BDNF) is a widespread neurotrophin implicated in cellular processes underlying memory, socialization, and emotion; however, little is known about how genetic modification of BDNF interacts with BDNF modulators (e.g., hormones) to regulate BDNF-TrkB signaling. BDNF binds to the TrkB receptor and triggers signaling cascades underlying neuroplasticity, learning, and memory. Inhibitory phosphorylation of one downstream target of the BDNF cascade - GSK3β – is also linked to memory improvements. The Val66Met allele – a single nucleotide polymorphism (SNP) in the Bdnf gene - produces impairments in regulated BDNF release from the cell, as well as deficits in spatial …

Revitalizing Alzheimer's Community Engagement In The Rgv Post-Pandemic: Insights From The First Two Alzheimer's Forums, Karla D. Lopez Lorenzo, Maxine Vieyra, Jesus D. Melgarejo, Gladys E. Maestre

Research Symposium

Background: The Rio Grande Valley (RGV), with a population predominantly composed of Hispanic/Latinos (93%), faces a higher risk of Alzheimer's Disease (AD) compared to other groups. The COVID-19 pandemic has highlighted the lack of education and awareness surrounding AD and related dementias in our community. To address these challenges, we partnered with the Alzheimer's Association to organize the first two Community Forums after the pandemic. Our goal is to raise awareness, provide resources, and support those affected by AD and related conditions in the RGV.

Methods: Through a proactive partnership, our objective was to meet the growing demand for education, …

Chronic Cannabis Use Is Associated With Decreased Treatment Response In Major Depression, Ihsan Salloum

Research Symposium

Background: Cannabis is the most frequently used federally illegal drug among the population and those receiving psychiatric treatment, including patients with major depression or alcohol use disorder. There is limited information on the impact of chronic cannabis use on treatment response. The aim of this study was to examine the rate of depression remission among patients with MDD and comorbid alcoholism who reported chronic cannabis abuse.

Methods: Sixty-four subjects with comorbid major depressive disorder and alcohol dependence (PRISM/DSM-IV), and a chronic (=>10 years) history of cannabis use (n=26) were compared to those who reported occasional or no cannabis …

Astrocytic Contribution To Motor Recovery After Spinal Cord Injury, Ellie Rice, Meifan Chen Phd

Posters-at-the-Capitol

Spinal cord injury results in loss of motor, sensory, and autonomic functions. Astrocytes, a cell type in the central nervous system, react to injury in a process called astrogliosis that impacts repair. At the site of injury, reactive astrocytes form an astrocytic scar that yields neuroprotective effects. Impaired formation of this scar causes increased tissue damage along with worsened motor recovery. Our lab identified leucine zipper-bearing kinase (LZK) as a key activator of astrogliosis that promotes wound healing after spinal cord injury in mice. This project examines the effect of astrocyte-specific LZK gene manipulation on hind-limb motor recovery following spinal …

Ephrinb2 Knockdown In Cervical Spinal Cord Preserves Diaphragm Innervation In A Mutant Sod1 Mouse Model Of Als, Mark W. Urban, Brittany A. Charsar, Nicolette M. Heinsinger, Shashirekha S. Markandaiah, Lindsay Sprimont, Wei Zhou, Eric V. Brown, Nathan T. Henderson, Samantha J. Thomas, Biswarup Ghosh, Rachel E. Cain, Davide Trotti, Piera Pasinelli, Megan C. Wright, Matthew B. Dalva, Angelo C. Lepore

Farber Institute for Neuroscience Staff Papers and Presentations

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by motor neuron loss. Importantly, non-neuronal cell types such as astrocytes also play significant roles in disease pathogenesis. However, mechanisms of astrocyte contribution to ALS remain incompletely understood. Astrocyte involvement suggests that transcellular signaling may play a role in disease. We examined contribution of transmembrane signaling molecule ephrinB2 to ALS pathogenesis, in particular its role in driving motor neuron damage by spinal cord astrocytes. In symptomatic SOD1G93A mice (a well-established ALS model), ephrinB2 expression was dramatically increased in ventral horn astrocytes. Reducing ephrinB2 in the cervical spinal cord ventral horn via …

Eaat4-Dependent Effects On Glutamatergic Signaling In The Cerebellar Molecular Layer, Christopher Chen

Dissertations (1934 -)

Glutamatergic signaling is fundamental to human behavior and its dysfunction is implicated in a wide range of neurological and neurodegenerative disorders. Excitatory amino-acid transporters (EAATs) – of which four primary subtypes (EAAT1, EAAT2, EAAT3, and EAAT4) exist in the human brain – are primary regulators of glutamate signaling. Endogenously-expressed at either low (EAAT4-low) or high (EAAT4-high) concentration in cerebellar Purkinje cells, EAAT4 has been shown to regulate Purkinje cell activity in the cerebellar molecular layer. However, differences in glutamatergic signaling at the circuit and single-synaptic levels in EAAT4-low and EAAT4-high regions are poorly understood. To characterize EAAT4-specific effects on excitatory …

Emerging Perspectives Of Synaptic Biomarkers In Als And Ftd, Karthik Krishnamurthy, Raj Kumar Pradhan

Farber Institute for Neuroscience Staff Papers and Presentations

Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) are debilitating neurodegenerative diseases with shared pathological features like transactive response DNA-binding protein of 43 kDa (TDP-43) inclusions and genetic mutations. Both diseases involve synaptic dysfunction, contributing to their clinical features. Synaptic biomarkers, representing proteins associated with synaptic function or structure, offer insights into disease mechanisms, progression, and treatment responses. These biomarkers can detect disease early, track its progression, and evaluate therapeutic efficacy. ALS is characterized by elevated neurofilament light chain (NfL) levels in cerebrospinal fluid (CSF) and blood, correlating with disease progression. TDP-43 is another key ALS biomarker, its mislocalization linked …

Alzheimer’S Disease And Microorganisms: The Non-Coding Rnas Crosstalk, Hanieh Mohammadi-Pilehdarboni, Mohammad Shenagari, Farahnaz Joukar, Hamed Naziri, Fariborz Mansour-Ghanaei

Department of Neurology Faculty Papers

Alzheimer’s disease (AD) is a complex, multifactorial disorder, influenced by a multitude of variables ranging from genetic factors, age, and head injuries to vascular diseases, infections, and various other environmental and demographic determinants. Among the environmental factors, the role of the microbiome in the genesis of neurodegenerative disorders (NDs) is gaining increased recognition. This paradigm shift is substantiated by an extensive body of scientific literature, which underscores the significant contributions of microorganisms, encompassing viruses and gut-derived bacteria, to the pathogenesis of AD. The mechanism by which microbial infection exerts its influence on AD hinges primarily on inflammation. Neuroinflammation, activated in …

Editorial: Neurotoxins In Alzheimer's Disease And Other Dementias, Alexandre Henriques, Philippe L. L. Poindron, Binosha Fernando, Kevin N. Hascup

Research outputs 2022 to 2026

Alzheimer's disease (AD) and other dementias are neurodegenerative disorders characterized by a progressive decline in cognition and independence from activities of daily living. Dementia is multifactorial with numerous risk factors including age, genes, molecules, lifestyle, and environmental contributions to disease onset and progression. In recent years, an emerging focus on neurotoxins has added a new layer of complexity to our understanding of dementia. This editorial aims to discuss recent updates regarding the role of neurotoxins in the pathogenesis of dementia.