Neurosciences Commons^™

Heightened Risk: Childhood Trauma And Anticipatory Grief Exacerbate The Impact Of Loneliness On Depressive Symptoms And Lps-Stimulated Cytokines In Dementia Caregivers, Kelly N Brice, Jensine Paoletti-Hatcher, E Lydia Wu-Chung, Vincent D Lai, Daniel L Argueta, Michelle A Chen, Itee Mahant, Bryan T Denny, Charles Green, Luis D Medina, Paul Schulz, Jennifer Stinson, Samantha K Henry, Cobi Heijnen, Christopher P Fagundes

Faculty, Staff and Student Publications

Dementia spousal caregivers are at a disproportionate risk for adverse mental and physical health outcomes. Loneliness is associated with depressive symptoms and proinflammatory cytokine production among caregivers. Additionally, childhood trauma, anticipatory grief, and poor sleep quality are all associated with enhanced stress reactivity. This study used a cross-sectional design to investigate whether loneliness is associated with proinflammatory cytokine production and depressive symptoms in caregivers, and whether these relationships are strongest among caregivers who report high levels of childhood trauma, high amounts of anticipatory grief, or poor sleep quality. A sample of 111 dementia spousal caregivers provided blood samples and completed …

Cognitive Performance In Early Neuronal Synuclein Disease With Hyposmia But Without Motor Disability: Association With Dopamine Deficiency And Isolated Rapid Eye Movement Sleep Behavior Disorder, Daniel Weintraub, Anuprita R Nair, Ryan Kurth, Michael C Brumm, Christine Kohnen, Michele K York, Roseanne D Dobkin, Kenneth Marek, Caroline Tanner, Tanya Simuni, Andrew Siderowf, Douglas Galasko, Lana M Chahine, Christopher Coffey, Kalpana Merchant, Kathleen L Poston, Tatiana Foroud, Brit Mollenhauer, Ethan G Brown, Karl Kieburtz, Mark Frasier, Sohini Chowdhury, Roy N Alcalay, Aleksandar Videnovic, Parkinson's Progression Markers Initiative

Faculty, Staff and Students Publications

Objective: To determine the impact of dopamine deficiency and isolated rapid eye movement (REM) sleep behavior disorder (iRBD) on cognitive performance in early neuronal α-synuclein disease (NSD) with hyposmia but without motor disability.

Methods: Using Parkinson's Progression Markers Initiative baseline data, cognitive performance was assessed with a cognitive summary score (CSS) derived from robust healthy control (HC) norms. Performance was examined for participants with hyposmia in early NSD-Integrated Staging System (NSD-ISS), either stage 2A (cerebrospinal fluid α-synuclein seed amplification assay [SAA]+, dopamine transporter scan [DaTscan]-) or 2B (SAA+, DaTscan+).

Results: Participants were stage 2A (n = 101), stage 2B (N …

Current Controversies In Prenatal Diagnosis 2: Conventional Postmortem Examination Remains The Gold Standard For The Anatomical Examination Of Fetal Loss, J Ciaran Hutchinson, Lorraine Potocki, Ignatia B Van Den Veyver

Duncan NRI Faculty and Staff Publications

A comprehensive postmortem examination is an essential component of a work-up after stillbirth. Its findings can support accurate counseling of parents about causes and risk of recurrence. It also supports providers' decisions about most appropriate testing and management plans for future pregnancy to prevent recurrence. Informing parents about fetal autopsy and obtaining their consent is challenging, and conducting a fetal autopsy requires expertise that is, not universally available. Newer non-invasive or minimally invasive methods such as postmortem MRI and targeted biopsies can replace or supplement autopsies, but one must recognize that expertise in these methods is likewise not broadly available. …

A Prospective, Randomized, Controlled Clinical Trial Of High-Frequency Electromagnetic Coupling Powered Permanent Peripheral Nerve Stimulator For The Treatment Of Chronic Craniofacial Pain, Salim M Hayek, Nameer Haider, Ashwin Viswanathan, Mehul Desai, Jeffrey Rosenberg, Niek E Vanquathem

Faculty, Staff and Students Publications

than one-fifth of the US population. While various medications and conservative treatment modalities are available for this condition, many patients have refractory symptoms. These patients suffer from social impairment, reduced quality of life, and increased financial burdens.

Objective: The objective of this study was to examine the clinical outcomes of patients receiving a permanent, high-frequency electromagnetic coupling (HF-EMC) powered peripheral nerve stimulator (PNS) system for the treatment of chronic craniofacial neuropathic pain.

Study design: This study was a multicenter, randomized, controlled clinical trial conducted under an investigational device exemption (IDE).

Setting: This study was conducted in 7 clinical sites in …

A Large-Scale Multi-Centre Study Characterising Atrophy Heterogeneity In Alzheimer's Disease, Vikram Venkatraghavan, Damiano Archetti, Pierrick Bourgeat, Chenyang Jiang, Mara Ten Kate, Anna C. Van Loenhoud, Rik Ossenkoppele, Charlotte E. Teunissen, Elsmarieke Van De Giessen, Yolande A.L. Pijnenburg, Giovanni B. Frisoni, Béla Weiss, Zoltán Vidnyánszky, Tibor Auer, Stanley Durrleman, Alberto Redolfi, Simon M. Laws, Paul Maruff, Neil P. Oxtoby, Andre Altmann, Daniel C. Alexander, Wiesje M. Van Der Flier, Frederik Barkhof, Betty M. Tijms

Research outputs 2022 to 2026

Previous studies identified atrophy-based Alzheimer's disease(AD) subtypes linked to distinct clinical symptoms, but their consistency across subtyping approaches remains unclear. This large-scale study evaluates subtype concordance using two data-driven approaches. In this work, we analyzed data from n=10,011 patients across 10 AD cohorts spanning Europe, the US, and Australia, extracting regional volumes using Freesurfer. To characterize atrophy heterogeneity in the AD continuum, we developed a two-step approach, Snowphlake (Staging NeurOdegeneration With PHenotype informed progression timeLine of biomarKErs), to identify subtypes and atrophy-event sequences within each subtype. Results were compared with SuStaIn (Subtype and Stage Inference), which jointly estimates subtypes and …

Moderate Coffee And Tea Consumption Is Associated With Slower Cognitive Decline, Stephanie R. Rainey-Smith, Kelsey R. Sewell, Belinda M. Brown, Hamid R. Sohrabi, Ralph N. Martins, Samantha L. Gardener

Research outputs 2022 to 2026

Background: Globally, coffee and tea are consumed extensively, potentially providing neuroprotection through anti-inflammatory and antioxidative stress effects. Objective: This study aimed to investigate associations between coffee and tea intake and cognitive function. Methods: In a longitudinal prospective cohort study, dementia-free (n = 8715; age range 60.0–85.2 years) older adults from the UK Biobank self-reported coffee and tea intake over the previous year; ‘never’, ‘moderate’ (1–3 cups/day), or ‘high’ (≥4 cups/day). Participants completed cognitive assessments at ≥2 timepoints (mean of 9.11 years). Results: Those ‘never’ consuming coffee and ‘moderate’ coffee consumers (β = 0.06, p = 0.005; β = 0.07, p <  0.001, respectively), as well as ‘moderate’ tea consumers and ‘high’ tea consumers (β = 0.06, p = 0.009; β = 0.06, p = 0.003, respectively) had slower fluid intelligence decline. Additionally, those ‘never’ consuming coffee and ‘moderate’ coffee consumers had a slower increase in pairs matching errors (β = −0.05, p = 0.022; β = 0.05, p = 0.013) compared to ‘high’ consumers. Conclusions: ‘Moderate’ coffee, and ‘moderate’ and ‘high’ tea intake may be a protective factor against cognitive decline. Randomized controlled trials are required to establish causal relationships leading to evidence-based recommendations regarding benefits of coffee and tea intake.

Risk Of Major Depression In Partners Of People With Alzheimer's Disease: A National Cohort Study, Casey Crump, Jingkai Wei, Barbara G Vickrey, Alexis C Edwards, Paul E Schulz, Weiva Sieh, Jan Sundquist, Kristina Sundquist

Faculty, Staff and Student Publications

Background: Alzheimer's disease (AD) may cause significant psychosocial distress not only in the patient but also their partner. However, long-term risks of major depression in partners of AD patients are largely unknown.

Methods: A national cohort study was conducted of all 145 289 partners of people diagnosed with all-cause dementia, including 57 113 partners of people diagnosed with AD, in Sweden during 1998-2017, and 1 300 561 population-based controls. Cox regression was used to compute hazard ratios (HRs) for subsequent risk of major depression identified from nationwide outpatient and inpatient diagnoses through 2018, adjusting for sociodemographic factors and prior mental …

Conventional Versus Advanced Imaging Selection For Endovascular Treatment Of Basilar Artery Occlusion Strokes, Huanwen Chen, Marco Colasurdo, Hidetoshi Matsukawa, Conor Cunningham, Ilko Maier, Sami Al Kasab, Pascal Jabbour, Joon-Tae Kim, Stacey Quintero Wolfe, Ansaar Rai, Robert M Starke, Marios-Nikos Psychogios, Edgar A Samaniego, Nitin Goyal, Shinichi Yoshimura, Hugo Cuellar, Jonathan A Grossberg, Ali Alawieh, Ali Alaraj, Mohamad Ezzeldin, Daniele G Romano, Omar Tanweer, Justin Mascitelli, Isabel Fragata, Adam Polifka, Fazeel Siddiqui, Joshua Osbun, Roberto Crosa, Charles Matouk, Min S Park, Michael R Levitt, Waleed Brinjikji, Mark Moss, Travis Dumont, Ergun Daglioglu, Richard Williamson, Pedro Navia, Reade De Leacy, Shakeel Chowdhry, David J Altschul, Alejandro M Spiotta, Peter Kan

Faculty, Staff and Students Publications

Introduction: Endovascular thrombectomy (EVT) is an effective treatment for basilar artery occlusion (BAO) stroke in select patients. While there is a growing body of literature suggesting that advanced imaging modalities such as computed tomography perfusion (CTP) and magnetic resonance (MR) may not be necessary for selecting anterior circulation large vessel occlusion stroke patients for EVT, whether advanced imaging may be superior to conventional imaging (non-contrast CT and CT angiography) in identifying good treatment candidates among BAO patients is less clear.

Patients and methods: This was a multicenter retrospective cohort study of BAO EVT patients treated from 2013 to 2022 in …

The 9th Annual Lafora Science Symposium: A Rare Epilepsy Community Makes Progress Towards Clinical Readiness, Meredith I. Williams, Katherine J. Donahue, Pascual Sanz, Souad Messahel, Jose M. Serratosa, Jordi Duran, Roberto Michelucci, Lorenzo Muccioli, Antonio Delgado-Escueta, Viet-Hong Nguyen, Berge A. Minassian, Matthew S. Gentry

Pharmacy Faculty Articles and Research

Lafora disease (LD) is a fatal childhood progressive myoclonus epilepsy and glycogen storage disease that is caused by recessive mutations in either EPM2A or EPM2B. The hallmarks of LD are cytoplasmic, aberrant glycogen-like aggregates, called Lafora bodies (LBs), that drive disease progression. The 9th Annual Lafora Science Symposium was held in San Diego, California and brought together over 70 researchers, clinicians, academic trainees, and friends and family members of patients with LD and 80 attendees joined virtually. This symposium focused primarily on international collaborations for therapeutic development and biomarker identification and strategies for preparing the Lafora community for upcoming …

Heterozygous Variants In Plcg1 Affect Hearing, Vision, Cardiac, And Immune Function, Mengqi Ma, Yiming Zheng, Mingxi Deng, Shenzhao Lu, Xueyang Pan, Xi Luo, Michelle Etoundi, David Li-Kroeger, Kim C Worley, Lindsay C Burrage, Lauren S Blieden, Aimee Allworth, Wei-Liang Chen, Giuseppe Merla, Barbara Mandriani, Catherine E Otten, Pierre Blanc, Jill A Rosenfeld, Debdeep Dutta, Shinya Yamamoto, Michael F Wangler, Ian A Glass, Jingheng Chen, Elizabeth Blue, Paolo Prontera, Jeremie Rosain, Sandrine Marlin, Seema R Lalani, Hugo J Bellen, Undiagnosed Diseases Network

Duncan NRI Faculty and Staff Publications

Phospholipase C isozymes (PLCs) hydrolyze phosphatidylinositol 4,5-bisphosphate (PIP₂) into inositol 1,4,5-trisphosphate (IP₃) and diacylglycerol (DAG), important signaling molecules involved in many cellular processes including Ca²⁺ release from the endoplasmic reticulum (ER). PLCG1 encodes the PLCγ1 isozyme that is broadly expressed. Hyperactive somatic mutations of PLCG1 are observed in multiple cancers, but only one germline variant has been reported. Here, we describe seven individuals with heterozygous missense variants in PLCG1 [p.(Asp1019Gly), p.(His380Arg), p.(Asp1165Gly), and p.(Leu597Phe)] who present with hearing impairment (5/7), ocular pathology (4/7), cardiac septal defects (3/6), and various immunological issues (5/7). To model these …

A Protective Role Of Src-1 Against Aging Associated Cognitive Decline, Hesong Liu, Yongjie Yang, Jonathan C Bean, Yang He, Hailan Liu, Rambabu Majji, Chen Liang, Nan Zhang, Meng Yu, Longlong Tu, Qingzhuo Liu, Yue Deng, Kristine M Conde, Na Yin, Mengjie Wang, Yongxiang Li, Junying Han, Sanika Vattakuzhiyil Jossy, Megan Elyse Burt, Hari Krishna Yalamanchili, Chunmei Wang

Duncan NRI Faculty and Staff Publications

Introduction: Research indicates a strong correlation between obesity and the risk of dementia, both are linked to steroid receptor coactivator-1 (SRC-1), a transcriptional coactivator.

Methods: We used RNA sequencing analysis (RNA-Seq) to investigate the transcriptome of SRC-1-KO mice, and identified S100 calcium-binding protein A6 (S100A6), an AD associated gene, as one target of SRC-1. We tested cognitive behaviors in SRC-1-KO mice and mice with a humanized SRC-1 mutation (SRC-1L1376P), and performed promoter luciferase assays on S100A6.

Results: Loss of SRC-1 caused alterations in gene signatures that are commonly associated with neurodegenerative diseases, including AD, and diminished the neural plasticity of …

Signaling By Intracellular Β2-Adrenergic Receptors Regulates Ampa Receptor Trafficking And Synaptic Plasticity, Boram Lee, Xiaomin Xing, Kyle E. Ireton, Bing Xu, Paul J. Gasser, Johannes W. Hell

Biomedical Sciences Faculty Research and Publications

Signaling by norepinephrine (NE) via adrenergic receptors (ARs) mediates attention, yet the underlying molecular mechanisms are largely unknown. AMPA receptors (AMPARs) form a complex with β2ARs, Gs, adenylyl cyclase, and protein kinase A (PKA) to augment AMPAR phosphorylation and, thereby, surface expression. We show that signaling by intracellular β2ARs is required for these effects and two different forms of long-term potentiation (LTP) that depend on β2AR signaling and phosphorylation of the AMPAR GluA1 subunit on S845. Inhibition of two NE transporters, the organic cation transporter 3 (OCT3) and the plasma membrane monoamine transporter (PMAT), impairs phosphorylation of the AMPAR GluA1 …

Mri-Guided Focused Ultrasound Thalamotomy For Neuropathic Pain In An Adolescent With Cranial Metastases: Illustrative Case, Sarah G Van Winkle, Danika L Paulo, Ashwin Viswanathan, Daniel Curry, Nisha Gadgil

Faculty, Staff and Students Publications

Background: Neuropathic cancer pain (NCP) is a debilitating condition that is often refractory to conventional medical management. MRI-guided focused ultrasound (MRgFUS) central lateral thalamotomy (CLT) is an incisionless neurosurgical option for neuropathic pain palliation, but its use in pediatric patients and those with cranial metastases, a relative contraindication to MRgFUS, remains largely unexamined.

Observations: A 16-year-old male with metastatic rhabdomyosarcoma (RMS) with numerous cranial metastases experienced severe, diffuse, refractory NCP. The patient underwent bilateral CLT with MRgFUS. After the procedure, the patient experienced complete and durable resolution of his neuropathic pain. He only reported occasional somatic pain at sites of …

Current Practices In The Study Of Biomolecular Acondensates: A Community Comment, Simon Alberti, Paolo Arosio, Robert B Best, Steven Boeynaems, Danfeng Cai, Rosana Collepardo-Guevara, Gregory L Dignon, Rumiana Dimova, Shana Elbaum-Garfinkle, Nicolas L Fawzi, Monika Fuxreiter, Amy S Gladfelter, Alf Honigmann, Ankur Jain, Jerelle A Joseph, Tuomas P J Knowles, Keren Lasker, Edward A Lemke, Kresten Lindorff-Larsen, Reinhard Lipowsky, Jeetain Mittal, Samrat Mukhopadhyay, Sua Myong, Rohit V Pappu, Karsten Rippe, Tatyana A Shelkovnikova, Anthony G Vecchiarelli, Susanne Wegmann, Huaiying Zhang, Mingjie Zhang, Chloe Zubieta, Markus Zweckstetter, Dorothee Dormann, Tanja Mittag

Duncan NRI Faculty and Staff Publications

The realization that the cell is abundantly compartmentalized into biomolecular condensates has opened new opportunities for understanding the physics and chemistry underlying many cellular processes, fundamentally changing the study of biology. The term biomolecular condensate refers to non-stoichiometric assemblies that are composed of multiple types of macromolecules in cells, occur through phase transitions, and can be investigated by using concepts from soft matter physics. As such, they are intimately related to aqueous two-phase systems and water-in-water emulsions. Condensates possess tunable emergent properties such as interfaces, interfacial tension, viscoelasticity, network structure, dielectric permittivity, and sometimes interphase pH gradients and electric potentials–. …

High-Grade Glioma With Pleomorphic And Pseudopapillary Features: A Single-Institution Series Of Three Cases, Eric A Goethe, Rasha Alfattal, Subhiksha Srinivasan, Pushan Dasgupta, Vinay Puduvalli, Shiao-Pei Weathers, Leomar Y Ballester, Jeffrey S Weinberg, Sujit Prabhu, Sherise D Ferguson, Maria A Gubbiotti

Faculty, Staff and Students Publications

Introduction: Modern molecular diagnostic techniques such as DNA methylation profiling are leading to the reclassification of several central nervous system malignancies and discovery of novel diagnostic entities, such as high-grade glioma with pleomorphic and pseudopapillary features (HPAP).

Methods: We performed a retrospective chart review of all patients with HPAP confirmed with methylation profiling at a single institution between 2023 and 2025. Demographic, radiographic, surgical, and outcome data were collected.

Results: Three patients were identified: two females and one male with a mean age of 49.7 years (range 25-62). No patients had a prior cancer history. One patient had an incidentally …

Prior Adolescent Oxycodone Exposure Enhances Pain Sensitivity Following Chronic Intermittent Ethanol In Adult Female Mice, Lisa L. Wilson, Lucas Albrechet-Souza, Linh Ha, Nicholas W. Gilpin, Tiffany A. Wills

School of Graduate Studies Faculty Publications

The opioid crisis remains a critical public health concern, with rising rates of overdose and opioid use disorder. While opioids are effective for managing pain, both chronic use and withdrawal are associated with increased pain sensitivity. Although most prior research has focused on adults, opioid use during adolescence is common and linked to a heightened risk for developing alcohol use disorder and other forms of substance misuse. Like opioids, acute alcohol use can be analgesic, but chronic alcohol exposure and withdrawal lead to increased pain sensitivity. However, the interactive effects of adolescent opioid and adult alcohol exposure on pain remain …

Transcriptomic And Epigenomic Profiling Of Immune Cells Responses To Simian Immunodeficiency Virus Infection In The Brain, Xiaoke Xu

Theses & Dissertations

Human immunodeficiency virus type 1 (HIV-1) is an enveloped retrovirus that significantly impairs the human immune system. A common complication of HIV-1 infection is HIV-associated neurocognitive disorder (HAND), which, prior to the introduction of antiretroviral therapy (ART), led to considerable morbidity and mortality due to untreated neuropsychiatric manifestations. Although ART has substantially reduced the incidence of HIV-associated dementia (HAD), approximately 50% of people living with HIV (PLWH) continue to experience milder forms of HAND. The CNS is seeded by HIV during the acute phase of infection. Once in the brain, HIV targets and activates resident immune cells, primarily microglia and …

The Speech-To-Song Illusion Across Development And The Effects Of High-Level Expectations, Rodica R. Constantine

UNLV Theses, Dissertations, Professional Papers, and Capstones

The typical listener can readily categorize auditory stimuli as either speech or song even though these structures share many acoustic similarities. These musical and linguistic categories may nevertheless take time to develop as children acquire language- and music-specific knowledge. In the Speech-to-Song (STS) illusion, multiple repetitions of a natural spoken utterance can give rise to a perceptual switch wherein the stimulus begins to sound song-like to the listener. While the STS illusion has been well-researched in adult listeners, it had yet to be investigated in children. In our study, we examined whether children experience the STS illusion by presenting participants …

Exploring The Processing Of Objects, Settings, And Global Properties In Natural Auditory Scenes, Margaret A. Mcmullin

UNLV Theses, Dissertations, Professional Papers, and Capstones

Our auditory system has a remarkable ability to make sense of complex environments, allowing us to identify what we are hearing and where sounds come from. This process of auditory scene analysis is essential for situational awareness, decision-making, and effective communication in daily life. While much is known about how listeners segregate and identify individual sound sources (e.g., voices), less is understood about how global properties of a scene (e.g., openness, naturalness) contribute to perception. This dissertation examined how object- and setting-level information in natural auditory scenes are processed, and whether they rely on distinct or overlapping mechanisms. In Experiment …

Botulinum Toxin For The Treatment Of Tremors, Steven Bellows, Joseph Jankovic

Faculty, Staff and Students Publications

Tremor, an oscillatory movement disorder, is commonly encountered in clinical practice in the setting of a variety of etiologies, such as essential tremor and Parkinson's disease. Despite its high prevalence, treatment options are somewhat limited. Oral medications are often ineffective or limited by side effects, and other treatments, such as deep brain stimulation, are more invasive and costly. Botulinum toxin (BoNT) injections are a well-established therapy in the treatment of dystonia, but its use in the treatment of tremors has not been fully explored. In this review, we discuss the available randomized controlled trials and open-label evidence for the use …

A Multi-Measurement Study Of The Relation Between Deliberation And Volition, Guillaume P. Pech, Emilie A. Caspar, Elisabeth Pacherie, Axel Cleeremans, Uri Maoz

Psychology Faculty Articles and Research

Historically, voluntary action and volition more generally have been investigated through the lens of meaningless decisions. Importantly, these findings have been used in the debate about key notions like free will and moral responsibility. However, more recent claims have challenged the possibility of generalizing findings from a meaningless context to a more meaningful one. The current study investigates the markers of volition, specifically comparing meaningful and meaningless decisions. In an effort to maximize their monetary gain, 50 participants repeatedly deliberated between two options, making either rewarded choices—hard-deliberation decisions (where the options differed along two dimensions) or easy-deliberation decisions (where the …

Rare Variants In Bmal1 Are Associated With A Neurodevelopmental Syndrome, Vishnu Anand Cuddapah, Dechun Chen, Bumsik Cho, Rebecca Moore, Mohnish Suri, Hana Safraou, Frederic Tran-Mau-Them, Ashley Wilson, Jacqueline Odgis, Atteeq U Rehman, Carol Saunders, Shiva Ganesan, Vaidehi Jobanputra, Stephen W Scherer, Ingo Helbig, Amita Sehgal

Duncan NRI Faculty and Staff Publications

Children with neurodevelopmental disorders exhibit highly penetrant sleep and circadian dysfunction, but the underlying mechanisms are unclear. We asked whether a subset of individuals with neurodevelopmental disorders might have genetic variants in genes known to drive circadian rhythms. Through international collaboration, we identified ten individuals with very rare genetic variants in BMAL1, a core component of the molecular clock. These individuals exhibited overlapping signs and symptoms including developmental delay, autism spectrum disorder, and variably penetrant marfanoid features. We functionally tested the identified BMAL1 variants in cell culture and in vivo and found disrupted BMAL1 function. These findings demonstrate that …

Upregulating Ankhd1 In Ps19 Mice Reduces Tau Phosphorylation And Mitigates Tau Toxicity-Induced Cognitive Deficits, Xiaolin Tian, Nathan Le, Yuhai Zhao, Dina Alawamleh, Andrew Schwartz, Lauren Meyer, Elizabeth Helm, Chunlai Wu

School of Graduate Studies Faculty Publications

Using the fly eye as a model system, we previously demonstrated that upregulation of the fly gene mask protects against FUS- and Tau-induced photoreceptor degeneration. Building upon this finding, we investigated whether the protective role of mask is conserved in mammals. To this end, we generated a transgenic mouse line carrying Cre-inducible ANKHD1, the human homolog of mask. Utilizing the TauP301S-PS19 mouse model for Tau-related dementia, we found that expressing ANKHD1 driven by CamK2a-Cre reduced hyperphosphorylated human Tau in 6-month-old mice. Additionally, ANKHD1 expression was associated with a trend toward reduced gliosis and preservation of the presynaptic marker Synaptophysin, suggesting …

Applications Of Preclinical Magnetic Resonance Imaging In The Treatment Of Traumatic Brain Injury And Understanding Carotid Artery Atherosclerosis, Evan Timothy Curtis

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

Advances in magnetic resonance imaging (MRI) provide the opportunity to investigate research questions that have been left unanswered. In the cases of traumatic brain injury (TBI) and carotid artery atherosclerosis, MRI is a resource for non-invasively viewing the phenomena taking place. Additionally, potential interventions and treatments can be observed without harm to the subject. This dissertation expands the understanding of two preclinical applications of MRI: traumatic brain injury and carotid artery atherosclerosis in mouse models.

TBI is a leading cause of death and disability for individuals between 15–45 years of age and effective pharmaceutical interventions for treating the secondary damage …

Effects Of Sex And Aging In The Response To Global Cerebral Hypoperfusion, Alexis Mcalister

Dissertations and Theses (Open Access)

Introduction

The prevalence of dementia worldwide is projected to double by the year 2030 and triple by 2050. Vascular cognitive impairment and dementia (VCID) encompasses diseases that lead to cognitive decline and dementia due to cerebrovascular disease. VCID is the second most common form of dementia after Alzheimer’s disease, accounting for approximately 15- 40% of all dementia cases. Reductions in cerebral blood flow from intracranial and extracranial atherosclerosis increase VCID risk, even in the absence of overt clinical or imaging evidence of stroke/embolization. The pathology seen in patients with chronic cerebral hypoperfusion, such as inflammation, neuronal loss, white matter abnormalities, …

Digital Pathology In Tau Research: A Comparison Of Qupath And Halo, Angelique D. Gonzalez, Yannick Joel Wadop Ngouongo, Benjamin Danner, Kyra M. Clarke, Matthew B. Dopler, Ali Ghaseminejad-Bandpey, Sahana Babu, Julie Parker-Garza, Cole Corbett, Gladys Maestre

School of Medicine Publications

The application of digital pathology tools has expanded in recent years, but non-neoplastic human brain tissue presents unique challenges due to its complexity. This study evaluated HALO and QuPath tau quantification performance in the hippocampus and mid-frontal gyrus across various tauopathies. Percent positivity emerged as the most reliable measure, showing strong correlations with Braak stages and CERAD scores, outperforming object and optical densities. QuPath demonstrated superior correlations with Braak stages, while HALO excelled in aligning with CERAD scoring. However, HALO’s optical density was less consistent. Paired t-tests revealed significant differences in object and optical densities between platforms, though percent positivity …

Rest-Activity Rhythm Phenotypes In Adults With Epilepsy And Intellectual Disability, Nandani Adhyapak, Grace E Cardenas, Mark A Abboud, Vaishnav Krishnan

Faculty, Staff and Students Publications

Objective: Rest-activity rhythms (RARs) are perturbed in many forms of neuropsychiatric illness. In this study, we applied wrist actigraphy to describe RAR perturbations in intellectually disabled adults with epilepsy ("E + ID"), using a cross-sectional case-control design. We examined whether RAR phenotypes correlated with epilepsy severity, deficits in adaptive function, and/or comorbid psychopathology.

Methods: Caregivers of E + ID subjects provided informed consent during routine ambulatory clinic visits and were asked to complete standardized surveys of overall epilepsy severity (GASE, Global Assessment of Severity of Epilepsy), adaptive function (ABAS-3, Adaptive Behavior Assessment System-3) and psychopathology (ABCL, Adult Behavior Checklist). Caregivers …

Genetic Diversity And Expanded Phenotypes In Dystonia: Insights From Large-Scale Exome Sequencing, Mirja Thomsen, Fabian Ott, Sebastian Loens, Gamze Kilic-Berkmen, Ai Huey Tan, Shen-Yang Lim, Ebba Lohmann, Kaja M Schröder, Lea Ipsen, Lena A Nothacker, Linn Welzel, Alexandra S Rudnik, Frauke Hinrichs, Thorsten Odorfer, Kirsten E Zeuner, Friederike Schumann, Andrea A Kühn, Simone Zittel, Marius Moeller, Robert Pfister, Christoph Kamm, Anthony E Lang, Yi Wen Tay, Ana Luísa De Almeida Marcelino, Marie Vidailhet, Emmanuel Roze, Joel S Perlmutter, Jeanne S Feuerstein, Victor S C Fung, Florence Chang, Richard L Barbano, Steven Bellows, Aparna A Wagle Shukla, Alberto J Espay, Mark S Ledoux, Brian D Berman, Stephen Reich, Andres Deik, Andre Franke, Michael Wittig, Sören Franzenburg, Jens Volkmann, Norbert Brüggemann, H A Jinnah, Tobias Bäumer, Christine Klein, Hauke Busch, Katja Lohmann

Faculty, Staff and Students Publications

Objective: Dystonia is one of the most prevalent movement disorders, characterized by significant clinical and etiological heterogeneity. Despite considerable heritability (~25%), the etiology in most patients remains elusive. Moreover, understanding correlations between clinical manifestations and genetic variants has become increasingly complex.

Methods: Exome sequencing was conducted on 1924 genetically unsolved, mainly late-onset isolated dystonia patients, recruited primarily from two dystonia registries (DysTract and the Dystonia Coalition). Rare variants in genes previously linked to dystonia (n = 406) were examined, confirmed via Sanger sequencing, and analyzed for segregation when possible.

Results: We identified 137 distinct likely pathogenic/pathogenic variants (according to ACMG …

The Synaptic Architecture Of Layer 5 Thick Tufted Excitatory Neurons In Mouse Visual Cortex, Agnes L Bodor, Casey M Schneider-Mizell, Chi Zhang, Leila Elabbady, Alex Mallen, Andi Bergeson, Derrick Brittain, Joann Buchanan, Daniel J Bumbarger, Rachel Dalley, Clare Gamlin, Emily Joyce, Daniel Kapner, Sam Kinn, Gayathri Mahalingam, Sharmishtaa Seshamani, Shelby Suckow, Marc Takeno, Russel Torres, Wenjing Yin, J Alexander Bae, Manuel A Castro, Sven Dorkenwald, Akhilesh Halageri, Zhen Jia, Chris Jordan, Nico Kemnitz, Kisuk Lee, Kai Li, Ran Lu, Thomas Macrina, Eric Mitchell, Shanka Subhra Mondal, Shang Mu, Barak Nehoran, Sergiy Popovych, William Silversmith, Nicholas L Turner, Szi-Chieh Yu, William Wong, Jingpeng Wu, Brendan Celii, Luke Campagnola, Stephanie C Seeman, Tim Jarsky, Naixin Ren, Anton Arkhipov, Jacob Reimer, H Sebastian Seung, R Clay Reid, Forrest Collman, Nuno Maçarico Da Costa

Faculty, Staff and Students Publications

Despite significant progress in characterizing neocortical cell types, a complete understanding of the synaptic connections of individual excitatory cells remains elusive. This study investigates the connectivity of mouse visual cortex thick tufted layer 5 pyramidal cells, also known as extratelencephalic neurons (L5-ETns), using a 1 mm3 publicly available electron microscopy dataset. The analysis reveals that, in their immediate vicinity, L5-ETns primarily establish connections with a group of inhibitory cell types, which, in turn, specifically target the L5-ETns back. The most common excitatory targets of L5-ETns are layer 5 intertelencephalic neurons (L5-ITns) and layer 6 (L6) pyramidal cells, whereas synapses with …

Folliculin Depletion Results In Liver Cell Damage And Cholangiocarcinoma Through Mit/Tfe Activation, Bruno Maria Custode, Francesco Annunziata, Felipe Dos Santos Matos, Valentina Schiano, Veronica Maffia, Milena Lillo, Rita Colonna, Rossella De Cegli, Andrea Ballabio, Nunzia Pastore

Duncan NRI Faculty and Staff Publications

Mutations in the tumor suppressor gene Folliculin (FLCN) are responsible for Birt-Hogg-Dube’ (BHD) syndrome, a rare inherited condition that predisposes affected individuals to skin tumors, pulmonary cysts, and kidney tumors. FLCN regulates key cellular pathways, including TFEB, TFE3, and mTORC1, which are critical for maintaining cell homeostasis. Loss of FLCN leads to both hyperactivation of mTORC1 and constitutive activation of TFEB and TFE3, contributing to tumorigenesis. While previous studies showed that Flcn liver-specific conditional knockout (FlcnLiKO) mice are protected from developing liver fibrosis and damage upon high-fat diet exposure, the potential role of FLCN loss in liver carcinogenesis …