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2024

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Articles 241 - 270 of 554

Full-Text Articles in Neurosciences

Assessment Of Brain-Derived Extracellular Vesicle Enrichment For Blood Biomarker Analysis In Age-Related Neurodegenerative Diseases: An International Overview, Amanpreet Badhwar, Yael Hirschberg, Natalia Valle-Tamayo, Florencia Iulita, Chinedu Momoh, Anna Matton, Rawan Tarawneh, Robert Rissman, Aurélie Ledreux, Charisse Winston Jun 2024

Assessment Of Brain-Derived Extracellular Vesicle Enrichment For Blood Biomarker Analysis In Age-Related Neurodegenerative Diseases: An International Overview, Amanpreet Badhwar, Yael Hirschberg, Natalia Valle-Tamayo, Florencia Iulita, Chinedu Momoh, Anna Matton, Rawan Tarawneh, Robert Rissman, Aurélie Ledreux, Charisse Winston

Brain and Mind Institute

INTRODUCTION Brain-derived extracellular vesicles (BEVs) in blood allows for minimally-invasive investigations of central nervous system (CNS) -specific markers of age-related neurodegenerative diseases (NDDs). Polymer-based EV- and immunoprecipitation (IP)-based BEV-enrichment protocols from blood have gained popularity. We systematically investigated protocol consistency across studies, and determined CNS-specificity of proteins associated with these protocols.

METHODS NDD articles investigating BEVs in blood using polymer-based and/or IP-based BEV enrichment protocols were systematically identified, and protocols compared. Proteins used for BEV-enrichment and/or post-enrichment were assessed for CNS- and brain-cell-type-specificity, extracellular domains (ECD+), and presence in EV-databases.

RESULTS A total of 82.1% of studies used polymer-based (ExoQuick) …


Flanker Task Performance In Young And Older Adults: A Behavioral And Erp Study, Fatima Medrano Jun 2024

Flanker Task Performance In Young And Older Adults: A Behavioral And Erp Study, Fatima Medrano

Dissertations, Theses, and Capstone Projects

Research suggests that as we get older, executive function abilities decline (Hasher & Zacks, 1988; Salthouse, 1996). One affected ability is that of inhibitory control, which aids in monitoring our responses to non-target stimuli or information. Current research on inhibition reveals inconsistencies across studies. Monitoring brain responses during the Flanker (used to measure inhibitory control) task may add valuable insight into the processes underlying group differences behaviorally, by studying the N200 and P300 event-related potentials which have been associated with inhibitory control processes. This study investigated whether there are differences between older and younger adults in inhibitory control and whether …


Polyvagal Theory For Kids: A Brain-Based Teaching Tool To Promote Coping, Katy Tenhulzen Jun 2024

Polyvagal Theory For Kids: A Brain-Based Teaching Tool To Promote Coping, Katy Tenhulzen

2024 Swedish Learning and Celebration Day

No abstract provided.


Incidence And Factors In Delayed Neurological Deficits After Subarachnoid Hemorrhage In Mice, William Wroe, Ari Dienel, Sungha Hong, Kanako Matsumura, Jose Guzman, Kiara Torres, Angelica Bernal, Hussein A Zeineddine, Peeyush Thankamani Pandit, Spiros L Blackburn, Devin W Mcbride Jun 2024

Incidence And Factors In Delayed Neurological Deficits After Subarachnoid Hemorrhage In Mice, William Wroe, Ari Dienel, Sungha Hong, Kanako Matsumura, Jose Guzman, Kiara Torres, Angelica Bernal, Hussein A Zeineddine, Peeyush Thankamani Pandit, Spiros L Blackburn, Devin W Mcbride

Faculty, Staff and Student Publications

Background: Delayed cerebral ischemia (DCI) is one of the most feared complications in aneurysmal subarachnoid hemorrhage (SAH). Animal models are crucial to studying the disease mechanisms and potential treatments. DCI in rodents was thought to not exist; herein we examine literature and our experience with DCI in rodents.

Methods: Daily behavioral performance was assessed every day from day 1 to up to 7 days post-SAH on mice from 5 different studies that used the endovascular perforation model. Performance was graded using an 8-test sensorimotor neuroscore previously described. The daily neuroscore was then used to identify the incidence and timing of …


A Thorough Examination Of Different Elisa Kits To Determine The Concentration Of S100b Linked To Intracranial Hemorrhage, Anthony Phan Jun 2024

A Thorough Examination Of Different Elisa Kits To Determine The Concentration Of S100b Linked To Intracranial Hemorrhage, Anthony Phan

University Honors Theses

Background: Traumatic Brain Injuries (TBI) and Intracranial Hemorrhages (ICH) are one of the leading causes of death. Faster diagnosis and treatment positively impact patient outcomes. Two protein markers (UCHL-1 and GFAP) were approved by the FDA as an indicator for prediction indicators of an ICH or moderate TBI.

Methods: In this project, the S100 Calcium Binding Protein B (S100B) was measured by performing an enzyme-linked immunoglobulin assay (ELISA) on the placebo arm of the Prehospital Tranexamic Acid Use for Traumatic Brain Injury" clinical trial. The aim of this project is to compare glial fibrillary acidic protein (GFAP) concentrations that were …


Purkinje Cell Dysfunction Causes Disrupted Sleep In Ataxic Mice, Luis E Salazar Leon, Amanda M Brown, Heet Kaku, Roy V Sillitoe Jun 2024

Purkinje Cell Dysfunction Causes Disrupted Sleep In Ataxic Mice, Luis E Salazar Leon, Amanda M Brown, Heet Kaku, Roy V Sillitoe

Duncan NRI Faculty and Staff Publications

Purkinje cell dysfunction disrupts movement and causes disorders such as ataxia. Recent evidence suggests that Purkinje cell dysfunction may also alter sleep regulation. Here, we used an ataxic mouse model generated by silencing Purkinje cell neurotransmission (L7Cre;Vgatfx/fx) to better understand how cerebellar dysfunction impacts sleep physiology. We focused our analysis on sleep architecture and electrocorticography (ECoG) patterns based on their relevance to extracting physiological measurements during sleep. We found that circadian activity was unaltered in the mutant mice, although their sleep parameters and ECoG patterns were modified. The L7Cre;Vgatfx/fx mutant mice had decreased wakefulness and rapid eye movement (REM) sleep, …


Adaptive, Behavioral, And Emotional Outcomes Following Postoperative Pediatric Cerebellar Mutism Syndrome In Survivors Treated For Medulloblastoma, Kimberly P Raghubar, Andrew M Heitzer, Fatema Malbari, Jason Gill, Roy V Sillitoe, Livia Merrill, Johanna Escalante, M Fatih Okcu, Guillermo Aldave, Avner Meoded, Stephen Kralik, Kimberly Davis, Marina Ma, Emily A H Warren, Mark D Mccurdy, Howard L Weiner, William Whitehead, Michael E Scheurer, Lisa Rodriguez, Amy Daigle, Murali Chintagumpala, Lisa S Kahalley Jun 2024

Adaptive, Behavioral, And Emotional Outcomes Following Postoperative Pediatric Cerebellar Mutism Syndrome In Survivors Treated For Medulloblastoma, Kimberly P Raghubar, Andrew M Heitzer, Fatema Malbari, Jason Gill, Roy V Sillitoe, Livia Merrill, Johanna Escalante, M Fatih Okcu, Guillermo Aldave, Avner Meoded, Stephen Kralik, Kimberly Davis, Marina Ma, Emily A H Warren, Mark D Mccurdy, Howard L Weiner, William Whitehead, Michael E Scheurer, Lisa Rodriguez, Amy Daigle, Murali Chintagumpala, Lisa S Kahalley

Faculty, Staff and Students Publications

OBJECTIVE: Patients who experience postoperative pediatric cerebellar mutism syndrome (CMS) during treatment for medulloblastoma have long-term deficits in neurocognitive functioning; however, the consequences on functional or adaptive outcomes are unknown. The purpose of the present study was to compare adaptive, behavioral, and emotional functioning between survivors with and those without a history of CMS.

METHODS: The authors examined outcomes in 45 survivors (15 with CMS and 30 without CMS). Comprehensive neuropsychological evaluations, which included parent-report measures of adaptive, behavioral, and emotional functioning, were completed at a median of 2.90 years following craniospinal irradiation.

RESULTS: Adaptive functioning was significantly worse in …


Sorghum Grain Polyphenolic Extracts Demonstrate Neuroprotective Effects Related To Alzheimer’S Disease In Cellular Assays Sorghum Grain Polyphenolic Extracts Demonstrate Neuroprotective Effects Related To Alzheimer’S Disease In Cellular Assays, Nasim Rezaee, Eugene Hone, Hamid R. Sohrabi, Stuart Johnson, Leizhou Zhong, Prakhar Chatur, Stuart Gunzburg, Ralph N. Martins, W. M.A.D.Binosha Fernando Jun 2024

Sorghum Grain Polyphenolic Extracts Demonstrate Neuroprotective Effects Related To Alzheimer’S Disease In Cellular Assays Sorghum Grain Polyphenolic Extracts Demonstrate Neuroprotective Effects Related To Alzheimer’S Disease In Cellular Assays, Nasim Rezaee, Eugene Hone, Hamid R. Sohrabi, Stuart Johnson, Leizhou Zhong, Prakhar Chatur, Stuart Gunzburg, Ralph N. Martins, W. M.A.D.Binosha Fernando

Research outputs 2022 to 2026

Sorghum grain contains high levels and a diverse profile of polyphenols (PPs), which are antioxidants known to reduce oxidative stress when consumed in the diet. Oxidative stress leading to amyloid-β (Aβ) aggregation, neurotoxicity, and mitochondrial dysfunction is implicated in the pathogenesis of Alzheimer’s disease (AD). Thus, PPs have gained attention as possible therapeutic agents for combating AD. This study aimed to (a) quantify the phenolic compounds (PP) and antioxidant capacities in extracts from six different varieties of sorghum grain and (b) investigate whether these PP extracts exhibit any protective effects on human neuroblastoma (BE(2)-M17) cells against Aβ- and tau-induced toxicity, …


Cognitive And Neuroscientific Perspectives Of Healthy Ageing, Jon B. Prince, Helen L. Davis, Jane Tan, Katrina Muller-Townsend, Shaun Markovic, David M. G. Lewis, Brianne Hastie, Matthew B. Thompson, Peter D. Drummond, Hakuei Fujiyama, Hamid R. Sohrabi Jun 2024

Cognitive And Neuroscientific Perspectives Of Healthy Ageing, Jon B. Prince, Helen L. Davis, Jane Tan, Katrina Muller-Townsend, Shaun Markovic, David M. G. Lewis, Brianne Hastie, Matthew B. Thompson, Peter D. Drummond, Hakuei Fujiyama, Hamid R. Sohrabi

Research outputs 2022 to 2026

With dementia incidence projected to escalate significantly within the next 25 years, the United Nations declared 2021–2030 the Decade of Healthy Ageing, emphasising cognition as a crucial element. As a leading discipline in cognition and ageing research, psychology is well-equipped to offer insights for translational research, clinical practice, and policy-making. In this comprehensive review, we discuss the current state of knowledge on age-related changes in cognition and psychological health. We discuss cognitive changes during ageing, including (a) heterogeneity in the rate, trajectory, and characteristics of decline experienced by older adults, (b) the role of cognitive reserve in age-related cognitive decline, …


Atp1a3 Disease Spectrum Includes Paroxysmal Weakness And Encephalopathy Not Triggered By Fever, Chetan Immanneni, Daniel Calame, Song Jiao, Lisa T Emrick, Miguel Holmgren, Sho T Yano Jun 2024

Atp1a3 Disease Spectrum Includes Paroxysmal Weakness And Encephalopathy Not Triggered By Fever, Chetan Immanneni, Daniel Calame, Song Jiao, Lisa T Emrick, Miguel Holmgren, Sho T Yano

Faculty, Staff and Students Publications

BACKGROUND AND OBJECTIVES: Heterozygous pathogenic variants in ATP1A3, which encodes the catalytic alpha subunit of neuronal Na+/K+-ATPase, cause primarily neurologic disorders with widely variable features that can include episodic movement deficits. One distinctive presentation of ATP1A3-related disease is recurrent fever-triggered encephalopathy. This can occur with generalized weakness and/or ataxia and is described in the literature as relapsing encephalopathy with cerebellar ataxia. This syndrome displays genotype-phenotype correlation with variants at p.R756 causing temperature sensitivity of ATP1A3. We report clinical and in vitro functional evidence for a similar phenotype not triggered by fever but associated with protein loss-of-function.

METHODS: We …


Prevention Of Dementia Using Mobile Phone Applications (Prodemos): A Multinational, Randomised, Controlled Effectiveness–Implementation Trial, Eric P.Moll Van Charante, Marieke P. Hoevenaar-Blom, Manshu Song, Sandrine Andrieu, Linda Barnes, Cindy Birck, Rachael Brooks, Nicola Coley, Esmé Eggink, Jean Georges, Melanie Hafdi, Willem A. Van Gool, Ron Handels, Haifeng Hou, Jihui Lyu, Yixuan Niu, Libin Song, Wenzhi Wang, Youxin Wang, Anders Wimo, Yueyi Yu, Jinxia Zhang, Wei Zhang, Carol Brayne, Wei Wang, Edo Richard Jun 2024

Prevention Of Dementia Using Mobile Phone Applications (Prodemos): A Multinational, Randomised, Controlled Effectiveness–Implementation Trial, Eric P.Moll Van Charante, Marieke P. Hoevenaar-Blom, Manshu Song, Sandrine Andrieu, Linda Barnes, Cindy Birck, Rachael Brooks, Nicola Coley, Esmé Eggink, Jean Georges, Melanie Hafdi, Willem A. Van Gool, Ron Handels, Haifeng Hou, Jihui Lyu, Yixuan Niu, Libin Song, Wenzhi Wang, Youxin Wang, Anders Wimo, Yueyi Yu, Jinxia Zhang, Wei Zhang, Carol Brayne, Wei Wang, Edo Richard

Research outputs 2022 to 2026

Background: The expected increase of dementia prevalence in the coming decades will mainly be in low-income and middle-income countries and in people with low socioeconomic status in high-income countries. This study aims to reduce dementia risk factors in underserved populations at high-risk using a coach-supported mobile health (mHealth) intervention. Methods: This open-label, blinded endpoint, hybrid effectiveness–implementation randomised controlled trial (RCT) investigated whether a coach-supported mHealth intervention can reduce dementia risk in people aged 55–75 years of low socioeconomic status in the UK or from the general population in China with at least two dementia risk factors. The primary effectiveness outcome …


Non-Invasive Brain Stimulation As Treatment For Motor Impairment In People With Parkinson's Disease: Protocol For An Umbrella Review, Dale M. Harris, Steven J. O'Bryan, Christopher Latella Jun 2024

Non-Invasive Brain Stimulation As Treatment For Motor Impairment In People With Parkinson's Disease: Protocol For An Umbrella Review, Dale M. Harris, Steven J. O'Bryan, Christopher Latella

Research outputs 2022 to 2026

Background Parkinson's disease (PD) is a progressive neurodegenerative disorder that predominantly affects movement and currently has no cure. Alongside medication, non-invasive brain stimulation (NIBS) may be used as an adjunct therapy to attenuate the motor symptoms experienced by people with PD. However, there is considerable heterogeneity in the evidence exploring the effects of NIBS for improving aspects of physical function in people with PD. Therefore, this protocol paper will outline the objectives, structure and procedure of a proposed umbrella review which will comprehensively summarise and map the current body evidence on the effectiveness of NIBS for improving physical function in …


Neurorehabilitation With Vagus Nerve Stimulation: A Systematic Review, Radha Korupolu, Alyssa Miller, Andrew Park, Nuray Yozbatiran May 2024

Neurorehabilitation With Vagus Nerve Stimulation: A Systematic Review, Radha Korupolu, Alyssa Miller, Andrew Park, Nuray Yozbatiran

Faculty, Staff and Student Publications

OBJECTIVE: To systematically review vagus nerve stimulation (VNS) studies to present data on the safety and efficacy on motor recovery following stroke, traumatic brain injury (TBI), and spinal cord injury (SCI).

METHODS: Data sources: PubMed, EMBASE, SCOPUS, and Cochrane.

STUDY SELECTION: Clinical trials of VNS in animal models and humans with TBI and SCI were included to evaluate the effects of pairing VNS with rehabilitation therapy on motor recovery.

DATA EXTRACTION: Two reviewers independently assessed articles according to the evaluation criteria and extracted relevant data electronically.

DATA SYNTHESIS: Twenty-nine studies were included; 11 were animal models of stroke, TBI, and …


Glioblastoma Disrupts Cortical Network Activity At Multiple Spatial And Temporal Scales, Jochen Meyer, Kwanha Yu, Estefania Luna-Figueroa, Benjamin Deneen, Jeffrey Noebels May 2024

Glioblastoma Disrupts Cortical Network Activity At Multiple Spatial And Temporal Scales, Jochen Meyer, Kwanha Yu, Estefania Luna-Figueroa, Benjamin Deneen, Jeffrey Noebels

Faculty, Staff and Students Publications

The emergence of glioblastoma in cortical tissue initiates early and persistent neural hyperexcitability with signs ranging from mild cognitive impairment to convulsive seizures. The influence of peritumoral synaptic density, expansion dynamics, and spatial contours of excess glutamate upon higher order neuronal network modularity is unknown. We combined cellular and widefield imaging of calcium and glutamate fluorescent reporters in two glioblastoma mouse models with distinct synaptic microenvironments and infiltration profiles. Functional metrics of neural ensembles are dysregulated during tumor invasion depending on the stage of malignant progression and tumor cell proximity. Neural activity is differentially modulated during periods of accelerated and …


Brain Cell-Type Shifts In Alzheimer’S Disease, Autism, And Schizophrenia Interrogated Using Methylomics And Genetics, Chloe X Yap, Daniel D Vo, Matthew G Heffel, Arjun Bhattacharya, Cindy Wen, Yuanhao Yang, Kathryn E Kemper, Jian Zeng, Zhili Zheng, Zhihong Zhu, Eilis Hannon, Dorothea Seiler Vellame, Alice Franklin, Christa Caggiano, Brie Wamsley, Daniel H Geschwind, Noah Zaitlen, Alexander Gusev, Bogdan Pasaniuc, Jonathan Mill, Chongyuan Luo, Michael J Gandal May 2024

Brain Cell-Type Shifts In Alzheimer’S Disease, Autism, And Schizophrenia Interrogated Using Methylomics And Genetics, Chloe X Yap, Daniel D Vo, Matthew G Heffel, Arjun Bhattacharya, Cindy Wen, Yuanhao Yang, Kathryn E Kemper, Jian Zeng, Zhili Zheng, Zhihong Zhu, Eilis Hannon, Dorothea Seiler Vellame, Alice Franklin, Christa Caggiano, Brie Wamsley, Daniel H Geschwind, Noah Zaitlen, Alexander Gusev, Bogdan Pasaniuc, Jonathan Mill, Chongyuan Luo, Michael J Gandal

Faculty, Staff and Student Publications

Few neuropsychiatric disorders have replicable biomarkers, prompting high-resolution and large-scale molecular studies. However, we still lack consensus on a more foundational question: whether quantitative shifts in cell types-the functional unit of life-contribute to neuropsychiatric disorders. Leveraging advances in human brain single-cell methylomics, we deconvolve seven major cell types using bulk DNA methylation profiling across 1270 postmortem brains, including from individuals diagnosed with Alzheimer's disease, schizophrenia, and autism. We observe and replicate cell-type compositional shifts for Alzheimer's disease (endothelial cell loss), autism (increased microglia), and schizophrenia (decreased oligodendrocytes), and find age- and sex-related changes. Multiple layers of evidence indicate that endothelial …


Incidence And Characteristics Of Cerebellar Atrophy/Volume Loss In Children With Confirmed Diagnosis Of Tuberous Sclerosis Complex, Livja Mertiri, Eugen Boltshauser, Stephen F Kralik, Nilesh K Desai, Maarten H Lequin, Thierry A G M Huisman May 2024

Incidence And Characteristics Of Cerebellar Atrophy/Volume Loss In Children With Confirmed Diagnosis Of Tuberous Sclerosis Complex, Livja Mertiri, Eugen Boltshauser, Stephen F Kralik, Nilesh K Desai, Maarten H Lequin, Thierry A G M Huisman

Faculty, Staff and Students Publications

Objectives: The goal of our study was to determine the incidence of cerebellar atrophy, assess the imaging findings in the posterior fossa and determine the incidence of hippocampal sclerosis in a cohort of pediatric patients with confirmed tuberous sclerosis complex (TSC).

Material and methods: MRI studies of 98 TSC pediatric patients (mean age 7.67 years) were evaluated for cerebellar atrophy, cerebral/cerebellar tubers, white matter lesions, subependymal nodules, subependymal giant cell astrocytomas, ventriculomegaly, and hippocampal sclerosis. Clinical charts were revisited for clinical symptoms suggesting cerebellar involvement, for seizures and treatment for seizures, behavioral disorders and autism.

Results: Cerebral tubers were present …


Generalizing Parkinson’S Disease Detection Using Keystroke Dynamics: A Self-Supervised Approach, Shikha Tripathi, Alejandro Acien, Ashley A Holmes, Teresa Arroyo-Gallego, Luca Giancardo May 2024

Generalizing Parkinson’S Disease Detection Using Keystroke Dynamics: A Self-Supervised Approach, Shikha Tripathi, Alejandro Acien, Ashley A Holmes, Teresa Arroyo-Gallego, Luca Giancardo

Faculty, Staff and Student Publications

Objective: Passive monitoring of touchscreen interactions generates keystroke dynamic signals that can be used to detect and track neurological conditions such as Parkinson's disease (PD) and psychomotor impairment with minimal burden on the user. However, this typically requires datasets with clinically confirmed labels collected in standardized environments, which is challenging, especially for a large subject pool. This study validates the efficacy of a self-supervised learning method in reducing the reliance on labels and evaluates its generalizability.

Materials and methods: We propose a new type of self-supervised loss combining Barlow Twins loss, which attempts to create similar feature representations with reduced …


Feasibility Of Fit24, A Digital Diabetes Prevention Program For Hispanic Adolescents: Qualitative Evaluation Study, Erica G Soltero, Salma M Musaad, Teresia M O'Connor, Debbe Thompson, Keith Norris, Bettina M Beech May 2024

Feasibility Of Fit24, A Digital Diabetes Prevention Program For Hispanic Adolescents: Qualitative Evaluation Study, Erica G Soltero, Salma M Musaad, Teresia M O'Connor, Debbe Thompson, Keith Norris, Bettina M Beech

Faculty, Staff and Students Publications

BACKGROUND: Digital health interventions are promising for reaching and engaging high-risk youth in disease prevention opportunities; however, few digital prevention interventions have been developed for Hispanic youth, limiting our knowledge of these strategies among this population.

OBJECTIVE: This study qualitatively assessed the feasibility and acceptability of Fit24, a 12-week goal-setting intervention that uses a Fitbit watch (Fitbit Inc) and theoretically grounded SMS text messages to promote physical activity and sleep among Hispanic adolescents (aged between 14 and 16 years) with obesity.

METHODS: After completing the intervention, a subsample of youth (N=15) participated in an in-depth interview. We categorized the themes …


Measurement Of And Contributors To Developmental Coordination Impairment, Jeffrey D. Konrad May 2024

Measurement Of And Contributors To Developmental Coordination Impairment, Jeffrey D. Konrad

WUSM Theses and Dissertations – All Programs

Movement drives childhood development. As motor skills improve across development, a child becomes capable of greater interactions with their physical and social environment. Children with motor impairments miss out on these interaction opportunities and their development across a variety of domains can suffer. There is accumulating evidence that poor motor competence relates to an array of developmental outcomes such as educational achievement, reading skills, social development, and emotional regulation. Two developmentally important motor impairments are poor motor competence and hyperactivity which are associated with Autism Spectrum Disorder (ASD), Developmental Coordination Disorder (DCD), and/or Attention Deficit Hyperactivity Disorder (ADHD). Critical to …


Transcriptomic Signature, Bioactivity And Safety Of A Non-Hepatotoxic Analgesic Generating Am404 In The Midbrain Pag Region, Hernan A. Bazan, Surjyadipta Bhattacharjee, Madigan M. Reid, Bokkyoo Jun, Connor Polk, Madeleine Strain, Linsey A. St Pierre, Neehar Desai, Patrick W. Daly, Jessica A. Cucinello-Ragland, Scott Edwards, Javier Recio, Julio Alvarez-Builla, James J. Cai, Nicolas G. Bazan May 2024

Transcriptomic Signature, Bioactivity And Safety Of A Non-Hepatotoxic Analgesic Generating Am404 In The Midbrain Pag Region, Hernan A. Bazan, Surjyadipta Bhattacharjee, Madigan M. Reid, Bokkyoo Jun, Connor Polk, Madeleine Strain, Linsey A. St Pierre, Neehar Desai, Patrick W. Daly, Jessica A. Cucinello-Ragland, Scott Edwards, Javier Recio, Julio Alvarez-Builla, James J. Cai, Nicolas G. Bazan

School of Medicine Faculty Publications

Safe and effective pain management is a critical healthcare and societal need. The potential for acute liver injury from paracetamol (ApAP) overdose; nephrotoxicity and gastrointestinal damage from chronic non-steroidal anti-inflammatory drug (NSAID) use; and opioids’ addiction are unresolved challenges. We developed SRP-001, a non-opioid and non-hepatotoxic small molecule that, unlike ApAP, does not produce the hepatotoxic metabolite N-acetyl-p-benzoquinone-imine (NAPQI) and preserves hepatic tight junction integrity at high doses. CD-1 mice exposed to SRP-001 showed no mortality, unlike a 70% mortality observed with increasing equimolar doses of ApAP within 72 h. SRP-001 and ApAP have comparable antinociceptive effects, including the complete …


Astrocytes Remember Inflammation, Michael R Williamson, Benjamin Deneen May 2024

Astrocytes Remember Inflammation, Michael R Williamson, Benjamin Deneen

Faculty, Staff and Students Publications

Astrocytes respond to all forms of central nervous system maladies. In a recent issue of Nature, Lee et al. demonstrate that astrocytes encode inflammatory stimuli as epigenetic memory, which strengthens responses to subsequent stimuli and exacerbates pathology in disease models.


Nrf2 Regulates Basal Gluathione Production In Astrocytes, Jiali He May 2024

Nrf2 Regulates Basal Gluathione Production In Astrocytes, Jiali He

Theses - ALL

In the central nervous system, astrocytes are the primary source of glutathione (GSH), an important and abundant non-protein thiol antioxidant. GSH biosynthesis takes place in the cytosol and involves two sequential steps, the first catalyzed by glutamate cysteine ligase (GCL) and the subsequent by glutathione synthetase (GSS). The process relies heavily on the availability of cysteine, which is obtained through the action of the glutamate/cystine antiporter, System xc-. This transporter imports cystine into the cells, where it is rapidly reduced to cysteine intracellularly for GSH synthesis. Furthermore, the multidrug resistance protein 1 (Mrp1) facilitates the export of GSH from astrocytes …


Fake Xanax: Designer Emerging Benzodiazepine Epidemic Linked To Morbidity And Mortality A Narrative Review, Alan D. Kaye, Joseph P. Tassin, William C. Upshaw, Camille M. Robichaux, Mark V. Frolov, Mark M. Dupaquier, Julia E. Fox, Jeffrey Sterritt, Jibin Mathew, Sahar Shekoohi, Adam M. Kaye, Amber N. Edinoff May 2024

Fake Xanax: Designer Emerging Benzodiazepine Epidemic Linked To Morbidity And Mortality A Narrative Review, Alan D. Kaye, Joseph P. Tassin, William C. Upshaw, Camille M. Robichaux, Mark V. Frolov, Mark M. Dupaquier, Julia E. Fox, Jeffrey Sterritt, Jibin Mathew, Sahar Shekoohi, Adam M. Kaye, Amber N. Edinoff

School of Dentistry Faculty Publications

Etizolam is a thienodiazepine derivative which produces an anxiolytic effect similar to benzodiazepines such as alprazolam (Xanax). Like classic benzodiazepines, etizolam has a high affinity towards the GABAA receptor, and allosterically potentiates the effects of GABA resulting in neuronal hyperpolarization related to chloride influx. When taken in therapeutic doses, etizolam produces a similar effect to Xanax. Counterfeit Xanax tablets contain variable amounts of etizolam. Tablets with high amounts of etizolam can cause toxicity if ingested, especially when combined with other substances. When toxic symptoms occur in patients, they may include severe sedation, unconsciousness, and depression of the medullary respiratory center. …


Clinical, Genetic, And Cognitive Correlates Of Seizure Occurrences In Phelan-Mcdermid Syndrome, Tess Levy, Jacob Gluckman, Paige M Siper, Danielle Halpern, Jessica Zweifach, Rajna Filip-Dhima, J Lloyd Holder, M Pilar Trelles, Kristina Johnson, Jonathan A Bernstein, Elizabeth Berry-Kravis, Craig M Powell, Latha Valluripalli Soorya, Audrey Thurm, Joseph D Buxbaum, Mustafa Sahin, Alexander Kolevzon, Siddharth Srivastava May 2024

Clinical, Genetic, And Cognitive Correlates Of Seizure Occurrences In Phelan-Mcdermid Syndrome, Tess Levy, Jacob Gluckman, Paige M Siper, Danielle Halpern, Jessica Zweifach, Rajna Filip-Dhima, J Lloyd Holder, M Pilar Trelles, Kristina Johnson, Jonathan A Bernstein, Elizabeth Berry-Kravis, Craig M Powell, Latha Valluripalli Soorya, Audrey Thurm, Joseph D Buxbaum, Mustafa Sahin, Alexander Kolevzon, Siddharth Srivastava

Duncan NRI Faculty and Staff Publications

Background: Phelan-McDermid syndrome (PMS) is a genetic neurodevelopmental disorder caused by SHANK3 haploinsufficiency and is associated with an increased risk for seizures. Previous literature indicates that around one third of individuals with PMS also have epilepsy or seizures, with a wide range of types and ages of onset. Investigating the impact of seizures on intellectual and adaptive functioning for PMS is a primary concern for caregivers and is important to understanding the natural history of this syndrome.

Methods: We report on results from 98 individuals enrolled in a prospective, longitudinal study. We detailed seizure frequency, type, and age of onset, …


Role Of Dunc-13 Isoforms In Alcohol Sensitivity In Drosophila, Makenzie Havard May 2024

Role Of Dunc-13 Isoforms In Alcohol Sensitivity In Drosophila, Makenzie Havard

Honors Theses

Functional alcohol tolerance is an adaptation made by the nervous system to high doses of alcohol, and is seen by a significant reduction in sensitivity to this drug. This tolerance is a significant contributing factor in the progression to Alcohol Use Disorders. A major goal of alcohol research is to understand how alcohol induces this tolerance. Dunc13 is a presynaptic active zone protein essential in synaptic vesicle docking and priming. Alcohol binds to the C1 domain of Dunc13 at physiological concentrations, which inhibits Dunc13 from binding Diacylglycerol. This inhibition is predicted to reduce Dunc13 activity and presynaptic activity. Yet, genetically …


Addressing Stroke Care Disparities Through Patient Education, Christina Annerino May 2024

Addressing Stroke Care Disparities Through Patient Education, Christina Annerino

Honors Capstones

It has been found across current studies and evaluations of stroke care and patient outcomes that there is a disparity in disability and mortality between male and female patients who have experienced stroke. The aforementioned studies did not identify the cause of this disparity, although a number of hypotheses for this phenomenon were provided. This study then conducted a preliminary survey of 130 participants, both men and women, aged 18-80 years old, to evaluate potential barriers to accessing stroke care and receiving treatment effectively. Preliminary survey data demonstrated consistent gaps in knowledge related to stroke risks, stroke symptoms, and when …


Healthy Aging Modulates The Neural Oscillatory Activity Underlying Basic Visual Processing And Verbal Working Memory, Seth D. Springer May 2024

Healthy Aging Modulates The Neural Oscillatory Activity Underlying Basic Visual Processing And Verbal Working Memory, Seth D. Springer

Theses & Dissertations

Worldwide economic and medical improvements have led to profound demographic shifts towards an older overall population. Unfortunately, with older age comes a variety of neurological changes which act to decrease individual quality of life and independence. Since the advent of functional neuroimaging, investigation of age-related changes in neural activity has been of particular interest. However, changes in population-level neural dynamics with age remain poorly characterized. Herein, we utilized magnetoencephalography (MEG), comprehensive neuropsychological assessments, and advanced analytical techniques to investigate spectrally-specific changes in neural oscillatory activity in a healthy aging population. First, we examined age-related deficiencies in visual processing using a …


An Actuarial Prediction Of Adhd Using Neuropsychological Data, Kimberlyn Williams May 2024

An Actuarial Prediction Of Adhd Using Neuropsychological Data, Kimberlyn Williams

Poster Presentations

Attention-Deficit/Hyperactivity Disorder (ADHD) is the most common psychiatric diagnosis in children and a frequent psychiatric diagnosis in adults. ADHD is a clinical diagnosis based on self-reported symptoms which makes accurate diagnosis challenging. Actuarial prediction has been demonstrated to be more accurate than clinical judgment. The current study explored an actuarial approach to predicting ADHD based on a comprehensive battery of neuropsychological tests. This project utilized test data from Meyers Neuropsychological Battery (MNB) to develop a logistic regression model to accurately predict diagnosed ADHD cases (n=65) from normal functioning cases (n=79) with a history of Mild Traumatic Brain Injury (mTBI). Binary …


Cognitive Control In Health And Disease: A Dynamic Approach To Mapping Oscillatory Activity Across The Lifespan, Mikki Schantell May 2024

Cognitive Control In Health And Disease: A Dynamic Approach To Mapping Oscillatory Activity Across The Lifespan, Mikki Schantell

Theses & Dissertations

Cognitive control is critical for flexibly adapting goal-directed behaviors to meet the demands of dynamically changing environments. The neural oscillatory dynamics serving cognitive control undergo changes across the lifespan, both in health and disease, with impairments in cognitive control functions being broadly implicated across a multitude of psychiatric disorders. Despite this, the trajectory of the population-level neural oscillatory dynamics supporting cognitive control across the lifespan remain poorly characterized, presenting challenges in fully understanding perturbations to these systems relative to one’s stage in neuronal maturation. Herein, we used the Eriksen flanker task during magnetoencephalographic (MEG) recording to map the neural oscillatory …


The Effect Of Repetitive Transcranial Magnetic Stimulation On Brain And Cognitive Variables In Patients With Amnestic Mild Cognitive Impairment, Connor J. Phipps May 2024

The Effect Of Repetitive Transcranial Magnetic Stimulation On Brain And Cognitive Variables In Patients With Amnestic Mild Cognitive Impairment, Connor J. Phipps

Theses & Dissertations

Healthy and pathological aging processes can impact human memory. Current interventions for clinical memory impairment offer little opportunity for restoration of memory ability. Fortunately, a novel therapy in the form of repetitive transcranial magnetic stimulation (rTMS) has exhibited promise in this regard. In healthy adults, rTMS of the angular gyrus (AG) has been reported to improve memory. The current study sought to determine the generalizability of these findings to individuals with clinical memory impairment by administering a clinical trial replicating an rTMS protocol reported to improve hippocampal-dependent memory in healthy individuals to individuals with amnestic mild cognitive impairment (aMCI). Individuals …