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Articles 91 - 120 of 152

Full-Text Articles in Neuroscience and Neurobiology

Behavioral Arrest And A Characteristic Slow Waveform Are Hallmark Responses To Selective 5-Ht2a Receptor Activation, April Contreras, Matthew Khumnark, Rochelle M. Hines, Dustin J. Hines Jan 2021

Behavioral Arrest And A Characteristic Slow Waveform Are Hallmark Responses To Selective 5-Ht2a Receptor Activation, April Contreras, Matthew Khumnark, Rochelle M. Hines, Dustin J. Hines

Psychology Faculty Research

© 2021, The Author(s). Perception, emotion, and mood are powerfully modulated by serotonin receptor (5-HTR) agonists including hallucinogens. The 5-HT2AR subtype has been shown to be central to hallucinogen action, yet the precise mechanisms mediating the response to 5-HT2AR activation remain unclear. Hallucinogens induce the head twitch response (HTR) in rodents, which is the most commonly used behavioral readout of hallucinogen pharmacology. While the HTR provides a key behavioral signature, less is known about the meso level changes that are induced by 5-HT2AR activation. In response to administration of the potent and highly selective 5-HT2AR agonist 25I-NBOH in mice, we …

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Prediction Of Alzheimer’S Disease-Specific Phospholipase C Gamma-1 Snv By Deep Learning-Based Approach For High-Throughput Screening, Sung Hyun Kim, Sumin Yang, Key Hwan Lim, Euiseng Ko, Hyun Jun Jang, Mingon Kang, Pann Ghill Suh, Jae Yeol Joo Jan 2021

Prediction Of Alzheimer’S Disease-Specific Phospholipase C Gamma-1 Snv By Deep Learning-Based Approach For High-Throughput Screening, Sung Hyun Kim, Sumin Yang, Key Hwan Lim, Euiseng Ko, Hyun Jun Jang, Mingon Kang, Pann Ghill Suh, Jae Yeol Joo

Computer Science Faculty Research

© 2021 National Academy of Sciences. All rights reserved. Exon splicing triggered by unpredicted genetic mutation can cause translational variations in neurodegenerative disorders. In this study, we discover Alzheimer’s disease (AD)-specific single-nucleotide variants (SNVs) and abnormal exon splicing of phospholipase c gamma-1 (PLCγ1) gene, using genome-wide association study (GWAS) and a deep learning-based exon splicing prediction tool. GWAS revealed that the identified single-nucleotide variations were mainly distributed in the H3K27ac-enriched region of PLCγ1 gene body during brain development in an AD mouse model. A deep learning analysis, trained with human genome sequences, predicted 14 splicing sites in human PLCγ1 gene, …

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Practical Recommendations For Timely, Accurate Diagnosis Of Symptomatic Alzheimer’S Disease (Mci And Dementia) In Primary Care: A Review And Synthesis, J. L. Liss, S. Seleri Assunção, Jeffrey Cummings, A. Atri, D. S. Geldmacher, S. F. Candela, D. P. Devanand, H. M. Fillit, J. Susman, J. Mintzer, T. Bittner, S. A. Brunton, D. R. Kerwin, W. C. Jackson, G. W. Small, G. T. Grossberg, C. K. Clevenger, V. Cotter, R. Stefanacci, A. Wise-Brown, M. N. Sabbagh Jan 2021

Practical Recommendations For Timely, Accurate Diagnosis Of Symptomatic Alzheimer’S Disease (Mci And Dementia) In Primary Care: A Review And Synthesis, J. L. Liss, S. Seleri Assunção, Jeffrey Cummings, A. Atri, D. S. Geldmacher, S. F. Candela, D. P. Devanand, H. M. Fillit, J. Susman, J. Mintzer, T. Bittner, S. A. Brunton, D. R. Kerwin, W. C. Jackson, G. W. Small, G. T. Grossberg, C. K. Clevenger, V. Cotter, R. Stefanacci, A. Wise-Brown, M. N. Sabbagh

School of Medicine Faculty Research

The critical role of primary care clinicians (PCCs) in Alzheimer’s disease (AD) prevention, diagnosis and management must evolve as new treatment paradigms and disease-modifying therapies (DMTs) emerge. Our understanding of AD has grown substantially: no longer conceptualized as a late-in-life syndrome of cognitive and functional impairments, we now recognize that AD pathology builds silently for decades before cognitive impairment is detectable. Clinically, AD first manifests subtly as mild cognitive impairment (MCI) due to AD before progressing to dementia. Emerging optimism for improved outcomes in AD stems from a focus on preventive interventions in midlife and timely, biomarker-confirmed diagnosis at early …

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Alzgps: A Genome-Wide Positioning Systems Platform To Catalyze Multi-Omics For Alzheimer’S Drug Discovery, Yadi Zhou, Jiansong Fang, Lynn M. Bekris, Yeon Heon Kim, Andrew A. Pieper, James B. Leverenz, Jeffrey Cummings, Feixiong Cheng Jan 2021

Alzgps: A Genome-Wide Positioning Systems Platform To Catalyze Multi-Omics For Alzheimer’S Drug Discovery, Yadi Zhou, Jiansong Fang, Lynn M. Bekris, Yeon Heon Kim, Andrew A. Pieper, James B. Leverenz, Jeffrey Cummings, Feixiong Cheng

School of Medicine Faculty Research

Background: Recent DNA/RNA sequencing and other multi-omics technologies have advanced the understanding of the biology and pathophysiology of AD, yet there is still a lack of disease-modifying treatments for AD. A new approach to integration of the genome, transcriptome, proteome, and human interactome in the drug discovery and development process is essential for this endeavor. Methods: In this study, we developed AlzGPS (Genome-wide Positioning Systems platform for Alzheimer’s Drug Discovery, https://alzgps.lerner.ccf.org), a comprehensive systems biology tool to enable searching, visualizing, and analyzing multi-omics, various types of heterogeneous biological networks, and clinical databases for target identification and development of effective prevention …

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A Conformation Variant Of P53 Combined With Machine Learning Identifies Alzheimer Disease In Preclinical And Prodromal Stages, Giulia Abate, Marika Vezzoli, Letizia Polito, Antonio Guaita, Diego Albani, Moira Marizzoni, Emirena Garrafa, Alessandra Marengoni, Gianluigi Forloni, Giovanni B. Frisoni, Jeffrey L. Cummings, Maurizio Memo, Daniela Uberti Dec 2020

A Conformation Variant Of P53 Combined With Machine Learning Identifies Alzheimer Disease In Preclinical And Prodromal Stages, Giulia Abate, Marika Vezzoli, Letizia Polito, Antonio Guaita, Diego Albani, Moira Marizzoni, Emirena Garrafa, Alessandra Marengoni, Gianluigi Forloni, Giovanni B. Frisoni, Jeffrey L. Cummings, Maurizio Memo, Daniela Uberti

School of Medicine Faculty Research

© 2020 by the authors. Li-censee MDPI, Basel, Switzerland. Early diagnosis of Alzheimer’s disease (AD) is a crucial starting point in disease man-agement. Blood-based biomarkers could represent a considerable advantage in providing AD-risk information in primary care settings. Here, we report new data for a relatively unknown blood-based biomarker that holds promise for AD diagnosis. We evaluate a p53-misfolding conformation rec-ognized by the antibody 2D3A8, also named Unfolded p53 (U-p532D3A8+), in 375 plasma samples derived from InveCe.Ab and PharmaCog/E-ADNI longitudinal studies. A machine learning approach is used to combine U-p532D3A8+ plasma levels with Mini-Mental State Examination (MMSE) and apolipoprotein E …

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Spatial Patterns Of Correlation Between Cortical Amyloid And Cortical Thickness In A Tertiary Clinical Population With Memory Deficit, Jagan A. Pillai, Mykol Larvie, Jacqueline Chen, Anna Crawford, Jeffery L. Cummings, Stephen E. Jones Dec 2020

Spatial Patterns Of Correlation Between Cortical Amyloid And Cortical Thickness In A Tertiary Clinical Population With Memory Deficit, Jagan A. Pillai, Mykol Larvie, Jacqueline Chen, Anna Crawford, Jeffery L. Cummings, Stephen E. Jones

School of Medicine Faculty Research

© 2020, The Author(s). To estimate regional Alzheimer disease (AD) pathology burden clinically, analysis methods that enable tracking brain amyloid or tau positron emission tomography (PET) with magnetic resonance imaging (MRI) measures are needed. We therefore developed a robust MRI analysis method to identify brain regions that correlate linearly with regional amyloid burden in congruent PET images. This method was designed to reduce data variance and improve the sensitivity of the detection of cortical thickness–amyloid correlation by using whole brain modeling, nonlinear image coregistration, and partial volume correction. Using this method, a cross-sectional analysis of 75 tertiary memory clinic AD …

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Association Between White Matter Hyperintensities, Cortical Thinning, And Clinical Outcomes In Mild Traumatic Brain Injury, Thomas Helmut Knoblauch Dec 2020

Association Between White Matter Hyperintensities, Cortical Thinning, And Clinical Outcomes In Mild Traumatic Brain Injury, Thomas Helmut Knoblauch

UNLV Theses, Dissertations, Professional Papers, and Capstones

Traumatic Brain Injury (TBI) is a global health challenge, with over 4.6 million confirmed cases annually in North America alone. Mild traumatic brain injuries (mTBIs) are the most common and make up approximately 81% of all TBI diagnoses worldwide [1]. Studies indicate that 10–15% of patients suffer from trauma induced symptoms (i.e. headache, loss of balance, cognitive impairments, fatigue, and mental health/affective disorders) as far as 1 year post injury [2]. Prediction and management of these post-traumatic sequalae is complicated by a lack of symptom associated neuroimaging findings. In spite of a “prominent distribution” of frontotemporal WMHs in pediatric subjects …

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Sex Moderates The Relationship That Number Of Professional Fights Has With Cognition And Brain Volumes, Lauren L. Bennett, Steve J. Stephen, Charles Bernick, Guogen Shan, Sarah J. Banks Oct 2020

Sex Moderates The Relationship That Number Of Professional Fights Has With Cognition And Brain Volumes, Lauren L. Bennett, Steve J. Stephen, Charles Bernick, Guogen Shan, Sarah J. Banks

School of Public Health Faculty Research

Objective: Incidence of concussions and report of symptoms are greater among women across sports. While structural brain changes and cognitive declines are associated with repetitive head impact (RHI), the role of sex is not well-understood. This study aimed to determine if there is a moderating effect of sex on the relationship the number of professional fights has with cognitive functioning and regional brain volumes in a cohort of boxers, mixed martial artists, and martial artists. Methods: A total of 55 women were matched with 55 men based on age, years of education, ethnicity, and fighting style. Cognition was assessed via …

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An Acute Application Of Cerebellar Transcranial Direct Current Stimulation Does Not Improve Motor Performance In Parkinson’S Disease, Lidio Lima De Albuquerque, Milan Pantovic, Mitchel Clingo, Katherine Fischer, Sharon Jalene, Merrill Landers, Zoltan Mari, Brach Poston Oct 2020

An Acute Application Of Cerebellar Transcranial Direct Current Stimulation Does Not Improve Motor Performance In Parkinson’S Disease, Lidio Lima De Albuquerque, Milan Pantovic, Mitchel Clingo, Katherine Fischer, Sharon Jalene, Merrill Landers, Zoltan Mari, Brach Poston

Integrated Health Sciences Faculty Research

Transcranial direct current stimulation of the cerebellum (c-tDCS) improves motor performance in young and old adults. Based on the cerebellar involvement in Parkinson’s disease (PD), c-tDCS could have potential to improve motor function in PD. The purpose was to determine the effects of c-tDCS on motor performance in PD while participants were on medications. The study was a randomized, double-blind, SHAM-controlled, between-subjects design. Twenty-two participants with PD were allocated to either a c-tDCS group or a SHAM group. All participants completed one experimental session and performed two motor tasks with their most affected hand in a Baseline condition (no stimulation) …

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Identification Of De Novo Mutations In Prenatal Neurodevelopment-Associated Genes In Schizophrenia In Two Han Chinese Patient-Sibling Family-Based Cohorts, Shan Jiang, Daizhan Zhou, Yin-Ying Wang, Peilin Jia, Chunling Wan, Xingwang Li, Guang He, Dongmei Cao, Xiaoqian Jiang, Kenneth S. Kendler, Ming Tsuang, Travis Mize, Jain-Shing Wu, Yimei Lu, Lin He, Jingchun Chen, Zhongming Zhao, Xiangning Chen Sep 2020

Identification Of De Novo Mutations In Prenatal Neurodevelopment-Associated Genes In Schizophrenia In Two Han Chinese Patient-Sibling Family-Based Cohorts, Shan Jiang, Daizhan Zhou, Yin-Ying Wang, Peilin Jia, Chunling Wan, Xingwang Li, Guang He, Dongmei Cao, Xiaoqian Jiang, Kenneth S. Kendler, Ming Tsuang, Travis Mize, Jain-Shing Wu, Yimei Lu, Lin He, Jingchun Chen, Zhongming Zhao, Xiangning Chen

School of Medicine Faculty Research

Schizophrenia (SCZ) is a severe psychiatric disorder with a strong genetic component. High heritability of SCZ suggests a major role for transmitted genetic variants. Furthermore, SCZ is also associated with a marked reduction in fecundity, leading to the hypothesis that alleles with large effects on risk might often occur de novo. In this study, we conducted whole-genome sequencing for 23 families from two cohorts with unaffected siblings and parents. Two nonsense de novo mutations (DNMs) in GJC1 and HIST1H2AD were identified in SCZ patients. Ten genes (DPYSL2, NBPF1, SDK1, ZNF595, ZNF718, GCNT2, SNX9, AACS, KCNQ1, and MSI2) were found to …

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Dementia-Related Psychosis And The Potential Role For Pimavanserin, Jeffery L. Cummings, D. P. Devanand, Stephen M. Stahl Aug 2020

Dementia-Related Psychosis And The Potential Role For Pimavanserin, Jeffery L. Cummings, D. P. Devanand, Stephen M. Stahl

School of Medicine Faculty Research

Dementia-related psychosis is prevalent across dementias and typically manifests as delusions and/or hallucinations. The mechanisms underlying psychosis in dementia are unknown; however, neurobiological and pharmacological evidence has implicated multiple signaling pathways and brain regions. Despite differences in dementia pathology, the neurobiology underlying psychosis appears to involve dysregulation of a cortical and limbic pathway involving serotonergic, GABAergic, glutamatergic, and dopaminergic signaling. Thus, an imbalance in cortical and mesolimbic excitatory tone may drive symptoms of psychosis. Delusions and hallucinations may result from (1) hyperactivation of pyramidal neurons within the visual cortex, causing visual hallucinations, and (2) hyperactivation of the mesolimbic pathway, causing …

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The Influence Of Cerebellar Transcranial Direct Current Stimulation On Motor Function In Parkinson’S Disease, Lidio Lima De Albuquerque Aug 2020

The Influence Of Cerebellar Transcranial Direct Current Stimulation On Motor Function In Parkinson’S Disease, Lidio Lima De Albuquerque

UNLV Theses, Dissertations, Professional Papers, and Capstones

Parkinson's disease (PD) is the most common movement disorder and the second most common neurodegenerative disorder. PD is characterized by dopaminergic cell loss in the substantia nigra pars compacta, which leads to a reduction in dopamine in the striatum. These physiological mechanisms lead to a number of motor impairments such as bradykinesia, rigidity, tremor, and postural instability that severely limit the ability of individuals with PD to perform many essential daily living activities. Although current pharmacological, surgical, and physical exercise treatment approaches are valuable they are either only mildly effective, expensive, or associated with a variety of side effects. Therefore, …

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Long-Term Impact Of Mild Traumatic Brain Injuries On Multiple Functional Outcomes And Epigenetics: A Pilot Study With College Students, Hyunhwa Lee, Sungchul Lee, Ipuna Black, Laura Salado, Jonica Estrada, Katrina Isla Jun 2020

Long-Term Impact Of Mild Traumatic Brain Injuries On Multiple Functional Outcomes And Epigenetics: A Pilot Study With College Students, Hyunhwa Lee, Sungchul Lee, Ipuna Black, Laura Salado, Jonica Estrada, Katrina Isla

Nursing Faculty Research

People who suffer a mild traumatic brain injury (mTBI) have heterogeneous symptoms and disease trajectories, which make it difficult to precisely assess long-term complications. This pilot study assessed and compared deficits in cognitive, psychosocial, visual functions, and balance performance between college students with and without histories of mTBI. Global DNA methylation ratio (5-mC%) in blood was also compared as a peripheral epigenetic marker. Twenty-five volunteers participated, including 14 healthy controls (64.3% females; mean age of 22.0) and 11 mTBI cases (27.3% females; mean age of 28.7 years) who self-reported mTBI history (63.6% multiple; 2.5 ± 1.29 injuries) with 7.1 years …

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Comatose Within 6 Weeks, But Still Alive After 3 Years, Creutzfeldt‐Jakob Disease With Unusual Progression, Julia Kathleen Christopher, Brian Khong, Amin Abolfazli, Antonio Liu Apr 2020

Comatose Within 6 Weeks, But Still Alive After 3 Years, Creutzfeldt‐Jakob Disease With Unusual Progression, Julia Kathleen Christopher, Brian Khong, Amin Abolfazli, Antonio Liu

School of Medicine Faculty Research

Creutzfeldt‐Jakob disease (CJD) should still be considered in a patient presenting with rapidly progressive dementia and negative CSF 14‐3‐3 protein and RT‐QulC. Treatable causes of encephalopathy must be ruled out. Neurodegenerative diseases must also be considered.

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Non-Amyloid Approaches To Disease Modification For Alzheimer’S Disease: An Eu/Us Ctad Task Force Report, Serge Gauthier, P. S. Aisen, J. Cummings, M. J. Detke, F. M. Longo, R. Raman, M. Sabbagh, L. Schneider, R. Tanzi, P. Tariot, M. Weiner, J. Touchon, B. Vellas Mar 2020

Non-Amyloid Approaches To Disease Modification For Alzheimer’S Disease: An Eu/Us Ctad Task Force Report, Serge Gauthier, P. S. Aisen, J. Cummings, M. J. Detke, F. M. Longo, R. Raman, M. Sabbagh, L. Schneider, R. Tanzi, P. Tariot, M. Weiner, J. Touchon, B. Vellas

School of Medicine Faculty Research

© 2020, The Author(s). While amyloid-targeting therapies continue to predominate in the Alzheimer’s disease (AD) drug development pipeline, there is increasing recognition that to effectively treat the disease it may be necessary to target other mechanisms and pathways as well. In December 2019, The EU/US CTAD Task Force discussed these alternative approaches to disease modification in AD, focusing on tau-targeting therapies, neurotrophin receptor modulation, anti-microbial strategies, and the innate immune response; as well as vascular approaches, aging, and non-pharmacological approaches such as lifestyle intervention strategies, photobiomodulation and neurostimulation. The Task Force proposed a general strategy to accelerate the development of …

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New Approaches To Symptomatic Treatments For Alzheimer’S Disease, Jeffrey Cummings Jan 2020

New Approaches To Symptomatic Treatments For Alzheimer’S Disease, Jeffrey Cummings

School of Medicine Faculty Research

Background: Successful development of agents that improve cognition and behavior in Alzheimer’s disease (AD) is critical to improving the lives of patients manifesting the symptoms of this progressive disorder. Discussion: There have been no recent approvals of cognitive enhancing agents for AD. There are currently 6 cognitive enhancers in Phase 2 trials and 4 in phase 3. They represent a variety of novel mechanisms. There has been progress in developing new treatments for neuropsychiatric symptoms in AD with advances in treatment of insomnia, psychosis, apathy, and agitation in AD. There are currently 4 AD-related psychotropic agents in Phase 2 trials …

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Alzheimer's Disease Drug Development Pipeline: 2020, Jeffrey Cummings, Garam Lee, Aaron Ritter, Marwan Sabbagh, Kate Zhong Jan 2020

Alzheimer's Disease Drug Development Pipeline: 2020, Jeffrey Cummings, Garam Lee, Aaron Ritter, Marwan Sabbagh, Kate Zhong

School of Medicine Faculty Research

© 2020 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association. Introduction: Alzheimer's disease (AD) is a growing public health concern affecting millions of patients worldwide and costing billions of dollars annually. We review the pipeline of drugs and biologics in clinical trials for the treatment of AD. We use the Common Alzheimer's and Related Dementias Research Ontology (CADRO) to classify treatment targets and mechanisms of action. We review our annual pipeline reports for the past 5 years to provide longitudinal insight into clinical trials and drug development for …

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Open Peer Commentary To “Failure To Demonstrate Efficacy Of Aducanumab: An Analysis Of The Emrge And Engage Trials As Reported By Biogen December 2019”, Marwan Noel Sabbagh, Jeffrey Cummings Jan 2020

Open Peer Commentary To “Failure To Demonstrate Efficacy Of Aducanumab: An Analysis Of The Emrge And Engage Trials As Reported By Biogen December 2019”, Marwan Noel Sabbagh, Jeffrey Cummings

School of Medicine Faculty Research

No abstract provided.

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Cognitively Normal Women With Alzheimer’S Disease Proteinopathy Show Relative Preservation Of Memory But Not Of Hippocampal Volume, Jessica Z.K. Caldwell, Jeffrey L. Cummings, Sarah J. Banks, Sebastian Palmqvist, Oskar Hansson Dec 2019

Cognitively Normal Women With Alzheimer’S Disease Proteinopathy Show Relative Preservation Of Memory But Not Of Hippocampal Volume, Jessica Z.K. Caldwell, Jeffrey L. Cummings, Sarah J. Banks, Sebastian Palmqvist, Oskar Hansson

School of Medicine Faculty Research

Background: We examined interactive effects of sex, diagnosis, and cerebrospinal fluid (CSF) amyloid beta/phosphorylated tau ratio (Aβ/P-tau) on verbal memory and hippocampal volumes. Methods: We assessed 682 participants (350 women) from BioFINDER (250 cognitively normal [CN]; and 432 symptomatic: 186 subjective cognitive decline [SCD], 246 mild cognitive impairment [MCI]). General linear models evaluated effects of Alzheimer’s disease (AD) proteinopathy (CSF Aß/p-tau ratio), diagnosis, and sex on verbal memory (ADAS-cog 10-word recall), semantic fluency (animal naming fluency), visuospatial skills (cube copy), processing speed/attention functions (Symbol Digit Modalities Test and Trail Making Part A), and hippocampal volumes. Results: Amyloid-positive (Aβ/P-tau+) CN women …

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Restructuring Of The Axon Initial Segment In Mouse Models Of Neurodevelopmental Disorders, Rachel Ali Rodriguez Dec 2019

Restructuring Of The Axon Initial Segment In Mouse Models Of Neurodevelopmental Disorders, Rachel Ali Rodriguez

UNLV Theses, Dissertations, Professional Papers, and Capstones

Neurodevelopmental disorders (NDDs) affect more than 36% of children in countries with low- and middle- incomes (Boivin, 2015; McCoy, 2016). Interestingly, these heterogeneous disorders share a high incidence of epileptic seizures, suggesting a shared pathology. Seizures result when neuronal firing activity becomes disturbed and neurons fire excessively or in unregulated patterns. A key site in the control of neuronal firing patterns is the axon initial segment (AIS), where the local density of proteins and the morphology of the AIS in part determine the firing of neurons. We hypothesized that a disruption in the morphology and/or composition of the AIS can …

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Biological And Practical Implications Of Genome-Wide Association Study Of Schizophrenia Using Bayesian Variable Selection, Benazir Rowe, Xiangning Chen, Zuoheng Wang, Jingchun Chen, Amei Amei Nov 2019

Biological And Practical Implications Of Genome-Wide Association Study Of Schizophrenia Using Bayesian Variable Selection, Benazir Rowe, Xiangning Chen, Zuoheng Wang, Jingchun Chen, Amei Amei

School of Medicine Faculty Research

Genome-wide association studies (GWAS) have identified over 100 loci associated with schizophrenia. Most of these studies test genetic variants for association one at a time. In this study, we performed GWAS of the molecular genetics of schizophrenia (MGS) dataset with 5334 subjects using multivariate Bayesian variable selection (BVS) method Posterior Inference via Model Averaging and Subset Selection (piMASS) and compared our results with the previous univariate analysis of the MGS dataset. We showed that piMASS can improve the power of detecting schizophrenia-associated SNPs, potentially leading to new discoveries from existing data without increasing the sample size. We tested SNPs in …

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Clinical Drug Development For Dementia With Lewy Bodies: Past And Present, Garam Lee, Jeffrey Cummings, Boris Decourt, James B. Leverenz, Marwan N. Sabbagh Oct 2019

Clinical Drug Development For Dementia With Lewy Bodies: Past And Present, Garam Lee, Jeffrey Cummings, Boris Decourt, James B. Leverenz, Marwan N. Sabbagh

School of Medicine Faculty Research

Introduction: Dementia with Lewy bodies (DLB) is an under-researched area despite being the second most common type of degenerative dementia after Alzheimer’s disease. It is an area of unmet need with no approved symptomatic or disease-modifying therapies. The pharmacological management of DLB is complex and challenging because early trials of drugs for DLB have resulted in no demonstrable efficacy. Randomized controlled trials (RCTs) in the DLB population have only recently been initiated. Understanding results from previous and current clinical trials in DLB can provide insights for future research and development. Areas covered: We provide an overview of the DLB drug …

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Neural Correlates Of Perceptual Switching While Listening To Bistable Auditory Streaming Stimuli, Nathan C. Higgins, David Frank Little, Breanne D. Yerkes, Karli M. Nave, Abin Kuruvilla-Mathew, M. Elhilai, Joel S. Snyder Sep 2019

Neural Correlates Of Perceptual Switching While Listening To Bistable Auditory Streaming Stimuli, Nathan C. Higgins, David Frank Little, Breanne D. Yerkes, Karli M. Nave, Abin Kuruvilla-Mathew, M. Elhilai, Joel S. Snyder

Psychology Faculty Research

Understanding the neural underpinning of conscious perception remains one of the primary challenges of cognitive neuroscience. Theories based mostly on studies of the visual system differ according to whether the neural activity giving rise to conscious perception occurs in modality-specific sensory cortex or in associative areas, such as the frontal and parietal cortices. Here, we search for modality-specific conscious processing in the auditory cortex using a bistable stream segregation paradigm that presents a constant stimulus without the confounding influence of physical changes to sound properties. ABA_ triplets (i.e., alternating low, A, and high, B, tones, and _ gap) with a …

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Sex Moderates Amyloid And Apolipoprotein Ε4 Effects On Default Mode Network Connectivity At Rest, Jessica Z.K. Caldwell, Xiaowei Zhuang, Mackenzie J. Leavitt, Sarah J. Banks, Jeffery Cummings, Dietmar Cordes Aug 2019

Sex Moderates Amyloid And Apolipoprotein Ε4 Effects On Default Mode Network Connectivity At Rest, Jessica Z.K. Caldwell, Xiaowei Zhuang, Mackenzie J. Leavitt, Sarah J. Banks, Jeffery Cummings, Dietmar Cordes

School of Medicine Faculty Research

Women are more likely to have Alzheimer's disease (AD) and decline more rapidly once diagnosed despite greater verbal memory early in the disease compared to men—an advantage that has been termed “memory reserve.” Resting state functional MRI (fMRI) investigations demonstrate interactions between sex and AD risk factors in default mode network (DMN) connectivity, a network of brain regions showing progressive dysfunction in AD. Separate work suggests connectivity of left prefrontal cortex (PFC) may correlate with more general cognitive reserve in healthy aging. It is unknown whether left prefrontal functional connectivity with anterior and posterior default mode network (aDMN, pDMN) might …

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Souvenaid In The Management Of Mild Cognitive Impairment: An Expert Consensus Opinion, Jeffrey Cummings, Peter Passmore, Bernadette Mcguinness, Vincent Mok, Christopher Chen, Sebastiaan Engelborghs, Michael Woodward, Sagrario Manzano, Guillermo Garcia-Ribas, Stefano Cappa, Paulo Bertolucci, Leung-Wing Chu Aug 2019

Souvenaid In The Management Of Mild Cognitive Impairment: An Expert Consensus Opinion, Jeffrey Cummings, Peter Passmore, Bernadette Mcguinness, Vincent Mok, Christopher Chen, Sebastiaan Engelborghs, Michael Woodward, Sagrario Manzano, Guillermo Garcia-Ribas, Stefano Cappa, Paulo Bertolucci, Leung-Wing Chu

School of Medicine Faculty Research

Background Mild cognitive impairment (MCI) among an aging global population is a growing challenge for healthcare providers and payers. In many cases, MCI is an ominous portent for dementia. Early and accurate diagnosis of MCI provides a window of opportunity to improve the outcomes using a personalized care plan including lifestyle modifications to reduce the impact of modifiable risk factors (for example, blood pressure control and increased physical activity), cognitive training, dietary advice, and nutritional support. Souvenaid is a once-daily drink containing a mixture of precursors and cofactors (long-chain omega-3 fatty acids, uridine, choline, B vitamins, vitamin C, vitamin E, …

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Meta-Analysis Of Cognitive Performance By Novel Object Recognition After Proton And Heavy Ion Exposures, Eliedonna Cacao, Francis A. Cucinotta Aug 2019

Meta-Analysis Of Cognitive Performance By Novel Object Recognition After Proton And Heavy Ion Exposures, Eliedonna Cacao, Francis A. Cucinotta

Health Physics and Diagnostic Sciences Faculty Research

Experimental studies of cognitive detriments in mice and rats after proton and heavy ion exposures have been performed by several laboratories to investigate possible risks to astronauts exposed to cosmic rays in space travel and patients treated for brain cancers with proton and carbon beams in Hadron therapy. However, distinct radiation types and doses, cognitive tests and rodent models have been used by different laboratories, while few studies have considered detailed dose-response characterizations, including estimates of relative biological effectiveness (RBE). Here we report on the first quantitative meta-analysis of the dose response for proton and heavy ion rodent studies of …

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Reduced Gabaergic Signaling At The Axon Initial Segment Decreases Vigilance State Transitioning, Austin John Boren Aug 2019

Reduced Gabaergic Signaling At The Axon Initial Segment Decreases Vigilance State Transitioning, Austin John Boren

UNLV Theses, Dissertations, Professional Papers, and Capstones

Sleep is a highly regulated homeostatic process that is disrupted in an estimated 50-70 million Americans. Regulation of sleep depends upon coordinated signaling of multiple neurotransmitter systems. In particular, inhibitory gamma-aminobutyric acid (GABA) signaling is required to suppress wake-active brain regions in order to initiate and maintain sleep states. GABA type A receptors (GABAARs) are ionotropic receptors with subunit compositions uniquely enriched on subcellular domains of target cells. α2 subunit-containing GABAARs are the primary target of GABA released onto the axon initial segment (AIS), a site critical for phasing the oscillatory activity of cortical cells. α2-containing GABAARs have previously been …

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Identification Of A Core Amino Acid Motif Within The Α Subunit Of Gabaars That Promotes Inhibitory Synaptogenesis And Resilience To Seizures, Anna J. Nathanson, Yihui Zhang, Joshua L. Smalley, Thomas A. Ollerhead, Miguel A. Rodriguez Santos, Peter M. Andrews, Heike J. Wobst, Yvonne E. Moore, Nicholas J. Brandon, Rochelle M. Hines, Paul A. Davies, Stephen J. Moss Jul 2019

Identification Of A Core Amino Acid Motif Within The Α Subunit Of Gabaars That Promotes Inhibitory Synaptogenesis And Resilience To Seizures, Anna J. Nathanson, Yihui Zhang, Joshua L. Smalley, Thomas A. Ollerhead, Miguel A. Rodriguez Santos, Peter M. Andrews, Heike J. Wobst, Yvonne E. Moore, Nicholas J. Brandon, Rochelle M. Hines, Paul A. Davies, Stephen J. Moss

Psychology Faculty Research

The fidelity of inhibitory neurotransmission is dependent on the accumulation of γ-aminobutyric acid type A receptors (GABAARs) at the appropriate synaptic sites. Synaptic GABAARs are constructed from α(1-3), β(1-3), and γ2 subunits, and neurons can target these subtypes to specific synapses. Here, we identify a 15-amino acid inhibitory synapse targeting motif (ISTM) within the α2 subunit that promotes the association between GABAARs and the inhibitory scaffold proteins collybistin and gephyrin. Using mice in which the ISTM has been introduced into the α1 subunit (Gabra1-2 mice), we show that the ISTM is critical for axo-axonic synapse formation, the efficacy of GABAergic …

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Resolving Intravoxel White Matter Structures In The Human Brain Using Regularized Regression And Clustering, Andrea Hart, Brianna Smith, Sean Smith, Elijah Sales, Jacqueline Hernandez-Camargo, Yarlin Mayor Garcia, Felix Zhan, Lori Griswold, Brian Dunkelberger, Michael R. Schwob, Sharang Chaudhry, Justin Zhan, Laxmi Gewali, Paul Oh Jul 2019

Resolving Intravoxel White Matter Structures In The Human Brain Using Regularized Regression And Clustering, Andrea Hart, Brianna Smith, Sean Smith, Elijah Sales, Jacqueline Hernandez-Camargo, Yarlin Mayor Garcia, Felix Zhan, Lori Griswold, Brian Dunkelberger, Michael R. Schwob, Sharang Chaudhry, Justin Zhan, Laxmi Gewali, Paul Oh

Computer Science Faculty Research

The human brain is a complex system of neural tissue that varies significantly between individuals. Although the technology that delineates these neural pathways does not currently exist, medical imaging modalities, such as diffusion magnetic resonance imaging (dMRI), can be leveraged for mathematical identification. The purpose of this work is to develop a novel method employing machine learning techniques to determine intravoxel nerve number and direction from dMRI data. The method was tested on multiple synthetic datasets and showed promising estimation accuracy and robustness for multi-nerve systems under a variety of conditions, including highly noisy data and imprecision in parameter assumptions.

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Molecular Specialization Of Gabaergic Synapses On The Soma And Axon In Cortical And Hippocampal Circuit Function And Dysfunction, April Contreras, Dustin J. Hines, Rochelle M. Hines Jun 2019

Molecular Specialization Of Gabaergic Synapses On The Soma And Axon In Cortical And Hippocampal Circuit Function And Dysfunction, April Contreras, Dustin J. Hines, Rochelle M. Hines

Psychology Faculty Research

The diversity of inhibitory interneurons allows for the coordination and modulation of excitatory principal cell firing. Interneurons that release GABA (γ-aminobutyric acid) onto the soma and axon exert powerful control by virtue of proximity to the site of action potential generation at the axon initial segment (AIS). Here, we review and examine the cellular and molecular regulation of soma and axon targeting GABAergic synapses in the cortex and hippocampus. We also describe their role in controlling network activity in normal and pathological states. Recent studies have demonstrated a specific role for postsynaptic dystroglycan in the formation and maintenance of cholecystokinin …

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