Medicine and Health Sciences 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 Available Information On The Gut-Brain Axis And Alzheimer’S Disease For Clinicians Making Dietary Recommendations: A Scoping Review, Megan Gibson

Electronic Theses and Dissertations

Abstract: Alzheimer’s Disease (AD) is a complex neurodegenerative disease that requires interprofessional collaboration. Pharmacological options are currently ineffective, increasing the need for preventative strategies to combat the rise of AD. Considerations of gut-targeted interventions have increased as a key component in the prevention of AD, based on the understanding that the state of the gut microbiome can impact cognitive function through the pathway known as the gut-brain axis.

Methods: This scoping review explored information on the gut-brain axis in persons with AD. A comprehensive search was conducted in November 2023. Forty reviews and 13 human studies were analyzed.

Results: There …

The Anatomical Embodiment Of Morning Routines In The Reduction Of Anxiety: An Intervention, Natalie Wright

Expressive Therapies Capstone Theses

The topic under investigation is whether physically embodying a morning routine that was designed through the lens of Laban Bartenieff Movement Analysis (LBMA) will reduce daily symptoms of individuals diagnosed with Generalized Anxiety Disorder.

Since morning routines play a significant part in one’s preparation for the day, I created an individualized LBMA morning routine for a specific client to embody. In addition to the routine, the client documented the process of their anxiety levels on a weekly basis. This client was a white, female, 19-year-old, lesbian college student who was previously diagnosed with Generalized Anxiety Disorder (GAD). The movement analysis …

The Effect Of The Glucocorticoid Receptor Modulator, Safit, On Acute Stress Reactivity In A Rat Model Of Abusive Head Trauma, Brielle Coe

Tower Health Research Day

No abstract provided.

In Silico Identification Of Small Molecule Agonist Binding Sites On Kcc2, Kenyon Mitchell, Alfred Amendolara, Ruth Hunter, Jaden Miner, Andrew Payne

Annual Research Symposium

Purpose: Potassium-Chloride Cotransporter 2 (KCC2) is a neuronal membrane protein specific to the central nervous system. It is responsible for removing Cl- ions from the intracellular space, maintaining a normal Cl- gradient essential for proper function at inhibitory synapses. Dysregulation causes an upward shift in the Cl- reversal potential resulting in a hyperexcitable state of the postsynaptic neuron. Existing literature indicates that KCC2 may be involved in the addiction pathway of a variety of drugs of abuse, including opioids and alcohol. This makes KCC2 an attractive potential drug target when treating substance use disorders. A novel direct KCC2 agonist, VU0500469, …

The Binding And Mechanism Of A Positive Allosteric Modulator Of Kv3 Channels, Qiansheng Liang, Gamma Chi, Leonardo Cirqueira, Lianteng Zhi, Agostino Marasco, Nadia Pilati, Martin Gunthorpe, Giuseppe Alvaro, Charles Large, David Sauer, Werner Treptow, Manuel Covarrubias

Farber Institute for Neuroscience Faculty Papers

Small-molecule modulators of diverse voltage-gated K⁺ (Kv) channels may help treat a wide range of neurological disorders. However, developing effective modulators requires understanding of their mechanism of action. We apply an orthogonal approach to elucidate the mechanism of action of an imidazolidinedione derivative (AUT5), a highly selective positive allosteric modulator of Kv3.1 and Kv3.2 channels. AUT5 modulation involves positive cooperativity and preferential stabilization of the open state. The cryo-EM structure of the Kv3.1/AUT5 complex at a resolution of 2.5 Å reveals four equivalent AUT5 binding sites at the extracellular inter-subunit interface between the voltage-sensing and pore domains of the …

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 …

Does Joint Angle Affect Composite, Inter-Individual, And Intra-Individual Patterns Of Responses For Men During Fatiguing Isometric Forearm Flexion Tasks Anchored To A High Perceptual Intensity?, Jocelyn E. Arnett, Robert W. Smith, Tyler J. Neltner, John Paul V. Anders, Dolores G. Ortega, Terry J. Housh, Richard J. Schmidt, Glen O. Johnson

Journal for Sports Neuroscience

Purpose: The purpose of this study was to utilize the Ratings of Perceived Exertion (RPE) Clamp Model to examine the effects of joint angle on the composite, inter-, and intra-individual patterns of responses for torque and neuromuscular parameters during fatiguing isometric tasks anchored to RPE of 8 (RPE = 8) at elbow joint angles of 75° (JA75) and 125° (JA125) for men. Methods: Ten men (Mean ± SD: age: 20.7 ± 1.2 yrs; height: 181.6 ± 6.0 cm; body mass: 83.7 ± 14.9 kg) performed 2,3 s forearm flexion maximal voluntary isometric contractions (MVIC) with the dominant arm before and …

A Potential Role Of Urinary P75ecd As A Biomarker For Amyotrophic Lateral Sclerosis In An American Cohort, Swati Dhasmana, Anupam Dhasmana, Sheema Khan, Acharan S. Narula, Murali Yallapu, Subhash Chauhan

Research Symposium

Background: Neurological disorders present a unique complexity compared to other diseases, involving multiple risk factors, causes, treatments, and outcomes. These disorders often exhibit various molecular and morphological changes indicative of disruptions in cellular plasticity and resilience. The pathogenesis of many neurological disorders remains unclear, necessitating ongoing investigations. Amyotrophic lateral sclerosis (ALS) exemplifies an idiopathic and fatal neurodegenerative disease marked by the degeneration of upper and lower motor neurons. The average life expectancy post-diagnosis is a mere 36 months, primarily attributed to respiratory muscle denervation.The persistent challenges in ALS clinical trials and the absence of effective therapeutic options have intensified interest …

Exploring The Developmental Effects Of Antidepressants In Caenorhabditis Elegans, Alexandra Van Stone

Annual Research Symposium

It is so important to explore the potential side effects of antidepressants especially if these side effects could lead to a future detriment to an individual’s financial and social well-being. A better understanding of these side effects in regards to human developmental issues is imperative considering issues related to mental health and depression affect a large percentage of the population. In this study, we tested if Caenorhabditis (C.) elegans could be a potential model organism to predict possible side effects associated with select antidepressants. Their developmental problems potentially encountered upon drug treatment may be encountered in humans.

Harmonious Healing: A Review Of Music Therapy, A Humanities-Based Approach To Alzheimer’S Disease Treatment, Rohan K. Desai

Kentucky Undergraduate Journal for the Health Humanities

Alzheimer’s Disease (AD) is a progressive neurodegenerative disease often characterized by memory loss, confusion, and overall cognitive decline. The aging global population has, in recent years, highlighted the fundamental lack of pharmacological treatments for individuals facing an AD diagnosis. In response, a growing body of research has shifted focus to non-pharmacological humanities-based interventions. One such intervention has been music therapy (MT). Music-focused measures have shown great promise as a method of slowing cognitive decline, but mixed results in the literature warrant the need for further investigation. Often, socioeconomic barriers can limit an individual’s access to drug-related treatments, but the affordable …

Birds, Bats And Minds. Tales Of A Revolutionary Scientist: Donald R. Griffin. Volume Three, Carolyn A. Ristau

eBooks

In this three-volume biography, we revisit the life and accomplishments of the revolutionary scientist, Donald R. Griffin. He encountered a lifetime of initial hostile resistance to his ideas and studies; now they are largely accepted. He and a colleague discovered the phenomenon of echolocation used by bats to navigate and capture insects, proposed that birds navigate guided by such cues as the sun and stars, and suggested that animals are likely aware, thinking and feeling beings. Forty interviews with his colleagues and friends help us understand the young emerging scientist and the mature researcher. We learn about his and others’ …

Methamphetamine-Induced Dna Double-Stranded Breaks: The Impact Of The Dopamine Transporter And Insights Into The Mechanisms Of Dna Damage In Mouse Neuro 2a Cells, Lizette Couto

Dissertations, Theses, and Capstone Projects

Methamphetamine (METH) abuse remains a global health concern, with emerging evidence highlighting its genotoxic potential. In the central nervous system METH enters dopaminergic cells primarily through the dopamine transporter (DAT), which controls the dynamics of dopamine (DA) neurotransmission by driving the reuptake of extracellular DA into the presynaptic neuronal cell. Additional effects of METH on the storage of DA in synaptic vesicles lead to the dysregulated cytosolic accumulation of DA. Previous studies have shown that after METH disrupts intracellular vesicular stores of DA, the excess DA in the cytosol is rapidly oxidized. This generates an abundance of reactive oxygen species …

Comparing Cognitive Tests And Smartphone-Based Assessment In 2 Us Community-Based Cohorts., Ileana De Anda-Duran, Preeti Sunderaraman, Edward Searls, Shirine Moukaled, Xuanyi Jin, Zachary Popp, Cody Karjadi, Phillip H Hwang, Huitong Ding, Sherral Devine, Ludy C Shih, Spencer Low, Honghuang Lin, Vijaya B Kolachalama, Lydia Bazzano, David J Libon, Rhoda Au

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

BACKGROUND: Smartphone-based cognitive assessments have emerged as promising tools, bridging gaps in accessibility and reducing bias in Alzheimer disease and related dementia research. However, their congruence with traditional neuropsychological tests and usefulness in diverse cohorts remain underexplored.

METHODS AND RESULTS: A total of 406 FHS (Framingham Heart Study) and 59 BHS (Bogalusa Heart Study) participants with traditional neuropsychological tests and digital assessments using the Defense Automated Neurocognitive Assessment (DANA) smartphone protocol were included. Regression models investigated associations between DANA task digital measures and a neuropsychological global cognitive

CONCLUSIONS: Our findings demonstrate that smartphone-based cognitive assessments exhibit concurrent validity with a …

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 Potential Of Stem Cell Therapy In Multiple Sclerosis Treatment: A Review, Sorina Amarculesei, Ava O'Meara Cushen, Cathy Brougham

SURE Journal: Science Undergraduate Research Experience Journal

Multiple Sclerosis is an autoimmune and neurodegenerative disease of the central nervous system. There are currently 2.8 million people living with Multiple Sclerosis worldwide, including 9000 people in Ireland, with a prevalence of 193 per 100,000 people. Symptoms of Multiple Sclerosis include sensory loss, fatigue, cognitive dysfunction, spasticity, depression, optic neuritis, gait ataxia, diplopia, and loss of bladder control. Currently, there is no standardised treatment or cure for Multiple Sclerosis with many strategies focusing on symptoms. Stem cells have emerged as promising approaches for Multiple Sclerosis therapeutics. Clinical trials primarily focus on mesenchymal stem cell-based therapies for Multiple Sclerosis. Furthermore, …

Nucleus Accumbens Core Single Cell Ensembles Bidirectionally Respond To Experienced Versus Observed Aversive Events, Oyku Dinckol, Noah Harris Wenger, Jennifer E Zachry, Munir Gunes Kutlu

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Fear learning is a critical feature of survival skills among mammals. In rodents, fear learning manifests itself through direct experience of the aversive event or social transmission of aversive stimuli such as observing and acting on conspecifics' distress. The neuronal network underlying the social transmission of information largely overlaps with the brain regions that mediate behavioral responses to aversive and rewarding stimuli. In this study, we recorded single cell activity patterns of nucleus accumbens (NAc) core neurons using in vivo optical imaging of calcium transients via miniature scopes. This cutting-edge imaging methodology not only allows us to record activity patterns …

Dna Methylation-Based Epigenetic Biomarkers In Cell-Type Deconvolution And Tumor Tissue Of Origin Identification, Ze Zhang

Dartmouth College Ph.D Dissertations

DNA methylation is an epigenetic modification that regulates gene expression and is essential to establishing and preserving cellular identity. Genome-wide DNA methylation arrays provide a standardized and cost-effective approach to measuring DNA methylation. When combined with a cell-type reference library, DNA methylation measures allow the assessment of underlying cell-type proportions in heterogeneous mixtures. This approach, known as DNA methylation deconvolution or methylation cytometry, offers a standardized and cost-effective method for evaluating cell-type proportions. While this approach has succeeded in discerning cell types in various human tissues like blood, brain, tumors, skin, breast, and buccal swabs, the existing methods have major …

Jun Upregulation Drives Aberrant Transposable Element Mobilization, Associated Innate Immune Response, And Impaired Neurogenesis In Alzheimer’S Disease, Chiara Scopa, Samantha Barnada, Maria Cicardi, Mo Singer, Davide Trotti, Marco Trizzino

Farber Institute for Neuroscience Faculty Papers

Adult neurogenic decline, inflammation, and neurodegeneration are phenotypic hallmarks of Alzheimer's disease (AD). Mobilization of transposable elements (TEs) in heterochromatic regions was recently reported in AD, but the underlying mechanisms are still underappreciated. Combining functional genomics with the differentiation of familial and sporadic AD patient derived-iPSCs into hippocampal progenitors, CA3 neurons, and cerebral organoids, we found that the upregulation of the AP-1 subunit, c-Jun, triggers decondensation of genomic regions containing TEs. This leads to the cytoplasmic accumulation of HERVK-derived RNA-DNA hybrids, the activation of the cGAS-STING cascade, and increased levels of cleaved caspase-3, suggesting the initiation of programmed cell death …

Central Activation Of Orl-1 Receptors In Heart Failure Models, Jeffrey Angell

Theses & Dissertations

Heart failure is a prevalent and debilitating disease associated with high morbidity and mortality rates worldwide and is the leading cause of death in the United States. While various therapeutic strategies have been developed and approved to manage heart failure, exploration of novel targets and mechanisms are essential for improving patient outcomes. This thesis investigates the therapeutic potential of the central activation of opioid receptor-like 1 (ORL-1) by nociceptin in a rodent heart failure model.

Furthermore, this study aims to elucidate the central mechanisms underlying nociceptin induced cardiovascular and renal effects in heart failure. This involves investigating neuronal pathways and …

Head Stabilization And Cortical Activation In Contact Sport Athletes During Walking Under Different Visual Task Constraints, Sam Zeff

Doctoral Dissertations

Contact sport participation exposes athletes to repetitive sub-concussive head impacts, which have been shown to elicit cortical neurophysiologic, cognitive, and motor performance alterations that have the potential to disrupt visual perception. Despite the growing concern regarding sub-concussive impacts, our understanding of their implications on motor performance and risk for further injury is limited. A stable head provides a consistent perceptual platform for the visual and vestibular sensory systems, but the effects of contact sport participation on head stability and visual perception remain poorly understood. The goal of this dissertation was to understand whether contact sport participation modifies athletes’ ability to …

No “Jitters” But No Energy From A Commercially Available Energy Drink., Jose Antonio, Jason M. Curtis

Journal for Sports Neuroscience

Abstract

Introduction: The purpose of this study was to determine the effects of an energy drink (JOCKO GO) on mood, sustained attention/reaction time, and hand steadiness.

Methods: A total of 29 active men (n = 9) and women (n=20) (mean ± SD: age 22 ± 5 yr.; height 168±8 cm; body mass 68.2 ± 12.8 kg; lean body mass 51.9 ± 15.0 kg; fat mass 15.4 ± 6.8 kg; percent body fat 22.6 ± 8.9%; total body water 38.6 ± 8.6 liters) completed this randomized, crossover, counterbalanced trial. Each subject consumed either one can (355 ml) of the energy …

Covid‑19‑Related Risk, Resilience, And Mental Health Among Mexican American Mothers Across The First Year Of The Pandemic, Amy L. Non, Elizabeth S. Clausing, Sandraluz Lara‑Cinisomo, Kimberly L. D’Anna Hernandez

Center for Brain, Biology, and Behavior: Faculty and Staff Publications

Background Latina mothers have been especially affected by the pandemic and historically exhibit high rates of depression and anxiety. However, few longitudinal studies have assessed the effect of the pandemic on this vulnerable population. We hypothesized that COVID-19-related stressors would associate with psychological distress among Latina mothers across the first year of the pandemic.

Methods We investigated COVID-19-related impact, stigma, and fears across two critical time points and changes in these measures in relation to changes in maternal anxiety and depression among mothers of Mexican descent living in Southern California (n=152). Surveys were administered within 5–16 weeks of …

Reduced Grey Matter Volume In Adolescents With Conduct Disorder: A Region‑Of‑Interest Analysis Using Multivariate Generalized Linear Modeling, Ru Zhang, R. James R. Blair, Karina S. Blair, Matthew Dobbertin, Jordan E. Pierce, Johannah Bashford‑Largo, Ahria J. Dominguez, Melissa Hatch, Sahil Bajaj

Center for Brain, Biology, and Behavior: Faculty and Staff Publications

Background Conduct disorder (CD) involves a group of behavioral and emotional problems that usually begins during childhood or adolescence. Structural brain alterations have been observed in CD, including the amygdala, insula, ventrolateral and medial prefrontal cortex, anterior cingulate cortex, and fusiform gyrus. The current study developed a multivariate generalized linear model (GLM) to differentiate adolescents with CD from typically developing (TD) adolescents in terms of grey matter volume (GMV).

Methods The whole‐brain structural MRI data were collected from 96 adolescents with CD (mean age = 16.188 ± 1.259 years; mean IQ = 104.292 ± 8.107 ; 63 males) and 90 …

Depaul Digest

DePaul Magazine

College of Education Professor Jason Goulah fosters hope, happiness and global citizenship through DePaul’s Institute for Daisaku Ikeda Studies in Education. Associate Journalism Professor Jill Hopke shares how to talk about climate change. News briefs from DePaul’s 10 colleges and schools: Occupational Therapy Standardized Patient Program, Financial Planning Certificate program, Business Education in Technology and Analytics Hub, Racial Justice Initiative, Teacher Quality Partnership grant, Intimate Partner Violence and Brain Injury collaboration, School of Music Career Closet, Sports Photojournalism course, DePaul Migration Collaborative’s Solutions Lab, Inclusive Screenwriting courses. New appointments: School of Music Dean John Milbauer, College of Education Dean Jennifer …

Insights Into The Molecular Roles Of Foxr2 In The Pathology Of Primary Pediatric Brain Tumors, Rajendra Gharbaran

Publications and Research

Forkhead box gene R2 (FOXR2) belongs to the family of FOX genes which codes for highly conserved transcription factors (TFs) with critical roles in biological processes ranging from development to organogenesis to metabolic and immune regulation to cellular homeostasis. A number of FOX genes are associated with cancer development and progression and poor prognosis. A growing body of evidence suggests that FOXR2 is an oncogene. Studies suggested important roles for FOXR2 in cancer cell growth, metastasis, and drug resistance. Recent studies showed that FOXR2 is overexpressed by a subset of newly identified entities of embryonal tumors. This review discusses the …

Sex Differences In Stress Reactivity, Brain Morphology, And Oxytocin In The Hypothalamus Of The Gray Short-Tailed Opossum (Monodelphis Domestica), Esperanza I. Zacarias, Daniela Rodriguez, Alexandra Chalons, Sasawan Heingraj, Nicole Altamirano, Joseph Rafac, John L. Vandeberg, Mario Gil

Research Colloquium

Understanding the effects of stress on behavior and cognition is important due to its impact on mental health and wellbeing (Schneiderman et al. 2005). Translational animal research can contribute to the development of new treatments that can improve therapeutic outcomes and our understanding of the neurobiology of stress. In the present study, we complement behavioral stress reactivity with immunohistochemical localization of oxytocin in the hypothalamus, a neuropeptide that regulates stress (Neumann & Slattery, 2016). Oxytocin has potential therapeutic use for mental health disorders (Neumann & Slattery, 2016), and the effects of oxytocin seem to be sexually dimorphic (Love, 2018). Using …

A Multi-Modal Imaging Analysis Of Inter-Community Hub Nodes In Subjective Cognitive Decline Linking Longitudinal Hub Function Disruption To White Matter Integrity Kurtosis, Duncan Nowling

MUSC Theses and Dissertations

Subjective Cognitive Decline (SCD) has garnered much interest as a potential identifiable preclinical stage and indicator of risk for cognitive decline in Alzheimer’s Disease and related dementias (ADRD). Identification of individuals in this stage though is difficult, as they present with objectively normal cognitive evaluation scores, relying instead upon self-report of concern about decline in cognitive abilities. The use of non-invasive in-vivo imaging methods like BOLD functional imaging and diffusion tensor have allowed for complex mapping of both the functional and structural network features unique to this condition. This study furthers this network biomarker map of SCD by investigating the …

Specialized Late Cingulo-Opercular Network Activation Elucidates The Mechanisms Underlying Decisions About Ambiguity, Jordan E. Pierce, Nathan M. Petro, Elizabeth Clancy, Caterina Gratton, Steven E. Petersen, Maital Neta

Center for Brain, Biology, and Behavior: Faculty and Staff Publications

Cortical task control networks, including the cingulo-opercular (CO) network play a key role in decision-making across a variety of functional domains. In particular, the CO network functions in a performance reporting capacity that supports successful task performance, especially in response to errors and ambiguity. In two studies testing the contribution of the CO network to ambiguity processing, we presented a valence bias task in which masked clearly and ambiguously valenced emotional expressions were slowly revealed over several seconds. This slow reveal task design provides a window into the decision-making mechanisms as they unfold over the course of a trial. In …

Investigating Monodelphis Domestica As An Alternative To The Mus Musculus As An Animal Model, Cristian M. Botello, John L. Vandeberg, Mario Gil

Research Symposium

Background: Mus Musculus is one of the first and one of the most widely used animal models in current neuroscience literature (Phifer-Riley & Nachmann, 2015). However, the research community needs alternatives to rodent models to study the mammalian brain. Research is needed to see if antibodies that target tyrosine hydroxylase, which are well researched in mice, can also be used to study the Monodelphis domestica brain.

Methods: Following transcardial perfusions and brain extractions, mouse and opossum brains were processed and stained for tyrosine hydroxylase (and with Nissl). Opossum brains will then be sliced and processed using IHC methods to compare …