Neurosciences Commons^™

Pathogenic Tau Accelerates Aging-Associated Activation Of Transposable Elements In The Mouse Central Nervous System, Paulino Ramirez, Gabrielle Zuniga, Wenyan Sun, Adrian Beckmann, Elizabeth Ochoa, Sarah L Devos, Bradley Hyman, Gabriel Chiu, Ethan R Roy, Wei Cao, Miranda Orr, Virginie Buggia-Prevot, William J Ray, Bess Frost

Faculty, Staff and Student Publications

Transposable elements comprise almost half of the mammalian genome. A growing body of evidence suggests that transposable element dysregulation accompanies brain aging and neurodegenerative disorders, and that transposable element activation is neurotoxic. Recent studies have identified links between pathogenic forms of tau, a protein that accumulates in Alzheimer's disease and related "tauopathies," and transposable element-induced neurotoxicity. Starting with transcriptomic analyses, we find that age- and tau-induced transposable element activation occurs in the mouse brain. Among transposable elements that are activated at the RNA level in the context of brain aging and tauopathy, we find that the endogenous retrovirus (ERV) class …

Editorial: How Can Wearable Robotic And Sensor Technology Advance Neurorehabilitation?, Shuo-Hsiu Chang, Shih-Chiao Tseng, Hao Su, Gerard E Francisco

Faculty, Staff and Student Publications

No abstract provided.

The Value Of Peer Support In Curbing Moral Injury: A Resident’S Perspective, May W Chen, Jennifer K Lee, Gilbert Vezina, Aylin Tekes, Jamie Perin, Ruoying Li, Alexandra O'Kane, Meaghan Mcgowan, Taeun Chang, Charlamaine Parkinson, Colleen Krein, Tareq Al-Shargabi, Frances J Northington, Ken M Brady, An N Massaro, Rathinaswamy B Govindan

Faculty, Staff and Student Publications

Identifying the hemodynamic range that best supports cerebral perfusion using near infrared spectroscopy (NIRS) autoregulation monitoring is a potential physiologic marker for neonatal hypoxic-ischemic encephalopathy (HIE) during therapeutic hypothermia. However, an optimal autoregulation monitoring algorithm has not been identified for neonatal clinical medicine. We tested whether the hemoglobin volume phase (HVP), hemoglobin volume (HVx), and pressure passivity index (PPI) identify changes in autoregulation that are associated with brain injury on MRI or death. The HVP measures the phase difference between a NIRS metric of cerebral blood volume, the total hemoglobin (THb), and mean arterial blood pressure (MAP) at the frequency …

Complete Corpus Callosotomy Using A Frameless Navigation Probe Through A Minicraniotomy In Children With Medically Refractory Epilepsy: A Case Series And Technical Note, Ahmed Belal, Gretchen Von Allmen, Indira Kommuru, Jeremy Lankford, John C Mosher, Manish Shah, Michael Funke, Michael Watkins, Rajan Patel

Faculty, Staff and Student Publications

BACKGROUND: Medically refractory epilepsy constitutes up to one-third of the epilepsy pediatric patients. Corpus callosotomy (CC) has been used for the treatment of medically refractory epilepsy in children with atonic seizures and generalized tonic-clonic (GTC) seizures. In this case series study, we are describing a novel technique for CC using the frameless navigation probe through a minicraniotomy.

METHODS: Thirteen pediatric patients with the diagnosis of medically refractory epilepsy predominantly GTC with drop attack who underwent extensive Phase I. An L-shape was done, then through a 4 × 3 cm craniotomy, we were able to open the interhemispheric fissure until the …

The Current Status And Shortcomings Of Stereotactic Radiosurgery, Hunter Mehrens, Trang Nguyen, Sharbacha Edward, Shannon Hartzell, Mallory Glenn, Daniela Branco, Nadia Hernandez, Paola Alvarez, Andrea Molineu, Paige Taylor, Stephen Kry

Faculty, Staff and Student Publications

Background: Stereotactic radiosurgery (SRS) is a common treatment for intracranial lesions. This work explores the state of SRS treatment delivery to characterize current treatment accuracy based on treatment parameters.

Methods: NCI clinical trials involving SRS rely on an end-to-end treatment delivery on a patient surrogate (credentialing phantom) from the Imaging and Radiation Oncology Core (IROC) to test their treatment accuracy. The results of 1072 SRS phantom irradiations between 2012 and 2020 were retrospectively analyzed. Univariate analysis and random forest models were used to associate irradiation conditions with phantom performance. The following categories were evaluated in terms of how they predicted …

Investigating The Mitochondrial Protein Mitoneet In C. Elegans Models Of Aging And Alzheimer's Disease, Jacob Ryan Boos

Graduate Theses, Dissertations, and Problem Reports (ETD)

Oxidative stress is an imbalance between reactive oxygen species production and elimination, favoring the former. Reactive oxygen species serve as important signaling molecules for physiological homeostasis. However, when produced in excess, these once important signaling molecules become detrimental, disrupting cellular functions, and ultimately leading to cell death. In aging, reactive oxygen species production is increased, accompanied with reductions in oxidative stress resistance, increasing the risk for developing age-related diseases including cardiovascular disease, cancer, stroke, and neurodegenerative diseases. The outer mitochondrial membrane iron-sulfur cluster containing protein mitoNEET (CISD1; gene CISD1) has shown to be a mediator of mitochondrial function and …

Recurrent Liponeurocytoma: A Case Report And Systematic Review Of The Literature, Darsh S Shah, Himanshu Sharma, Prem Patel, Arya Shetty, Collin William English, J Clay Goodman, Ashwin Viswanathan, Akash J Patel

Duncan NRI Faculty and Staff Publications

Background: Liponeurocytomas are rare neurocytic neoplasms that most often arise in the posterior fossa and affect individuals in the third and fifth decades of life. Most reported cases of this unique tumor in the literature have described a favorable clinical prognosis without recurrence. However, increasing reports of recurrent cases prompted the World Health Organization, in 2016, to recategorize the tumor from Grade I to the less favorable Grade II classification. We conducted a systematic review to identify recurrent cases of this unique tumor and to summarize differences between the primary and recurrent cases of liponeurocytoma.

Methods: A systematic review exploring …

Functional Studies Of Genetic Variants Associated With Human Diseases In Notch Signaling-Related Genes Using Drosophila, Sheng-An Yang, Jose L Salazar, David Li-Kroeger, Shinya Yamamoto

Duncan NRI Faculty and Staff Publications

Rare variants in the many genes related to Notch signaling cause diverse Mendelian diseases that affect myriad organ systems. In addition, genome- and exome-wide association studies have linked common and rare variants in Notch-related genes to common diseases and phenotypic traits. Moreover, somatic mutations in these genes have been observed in many types of cancer, some of which are classified as oncogenic and others as tumor suppressive. While functional characterization of some of these variants has been performed through experimental studies, the number of ‘variants of unknown significance’ identified in patients with diverse conditions keeps increasing as high-throughput sequencing technologies …

Epithelial Morphogenesis In The Drosophila Egg Chamber Requires Parvin And Ilk, Athina Keramidioti, Evgenia Golegou, Eleni Psarra, Nikolaos Paschalidis, Konstantina Kalodimou, Shinya Yamamoto, Christos Delidakis, Katerina M Vakaloglou, Christos G Zervas

Duncan NRI Faculty and Staff Publications

Integrins are the major family of transmembrane proteins that mediate cell-matrix adhesion and have a critical role in epithelial morphogenesis. Integrin function largely depends on the indirect connection of the integrin cytoplasmic tail to the actin cytoskeleton through an intracellular protein network, the integrin adhesome. What is currently unknown is the role of individual integrin adhesome components in epithelia dynamic reorganization. Drosophila egg chamber consists of the oocyte encircled by a monolayer of somatic follicle epithelial cells that undergo specific cell shape changes. Egg chamber morphogenesis depends on a developmental array of cell-cell and cell-matrix signalling events. Recent elegant work …

Emerging Roles Of Alternative Cleavage And Polyadenylation (Apa) In Human Disease, Prakash Dharmalingam, Rajasekaran Mahalingam, Hari Krishna Yalamanchili, Tingting Weng, Harry Karmouty-Quintana, Ashrith Guha, Rajarajan A Thandavarayan

Duncan NRI Faculty and Staff Publications

In the messenger RNA (mRNA) maturation process, the 3'-end of pre-mRNA is cleaved and a poly(A) sequence is added, this is an important determinant of mRNA stability and its cellular functions. More than 60%-70% of human genes have three or more polyadenylation (APA) sites and can be cleaved at different sites, generating mRNA transcripts of varying lengths. This phenomenon is termed as alternative cleavage and polyadenylation (APA) and it plays role in key biological processes like gene regulation, cell proliferation, senescence, and also in various human diseases. Loss of regulatory microRNA binding sites and interactions with RNA-binding proteins leading to …

In Alzheimer-Prone Brain Regions, Metabolism And Risk-Gene Expression Are Strongly Correlated, Fengdan Ye, Quentin Funk, Elijah Rockers, Joshua M Shulman, Joseph C Masdeu, Belen Pascual

Duncan NRI Faculty and Staff Publications

Neuroimaging in the preclinical phase of Alzheimer’s disease provides information crucial to early intervention, particularly in people with a high genetic risk. Metabolic network modularity, recently applied to the study of dementia, is increased in Alzheimer’s disease patients compared with controls, but network modularity in cognitively unimpaired elderly with various risks of developing Alzheimer’s disease needs to be determined. Based on their 5-year cognitive progression, we stratified 117 cognitively normal participants (78.3 ± 4.0 years of age, 52 women) into three age-matched groups, each with a different level of risk for Alzheimer’s disease. From their fluorodeoxyglucose PET we constructed metabolic …

Advancements In The Quest To Map, Monitor, And Manipulate Neural Circuitry, Jessica L Swanson, Pey-Shyuan Chin, Juan M Romero, Snigdha Srivastava, Joshua Ortiz-Guzman, Patrick J Hunt, Benjamin R Arenkiel

Duncan NRI Faculty and Staff Publications

Neural circuits and the cells that comprise them represent the functional units of the brain. Circuits relay and process sensory information, maintain homeostasis, drive behaviors, and facilitate cognitive functions such as learning and memory. Creating a functionally-precise map of the mammalian brain requires anatomically tracing neural circuits, monitoring their activity patterns, and manipulating their activity to infer function. Advancements in cell-type-specific genetic tools allow interrogation of neural circuits with increased precision. This review provides a broad overview of recombination-based and activity-driven genetic targeting approaches, contemporary viral tracing strategies, electrophysiological recording methods, newly developed calcium, and voltage indicators, and neurotransmitter/neuropeptide biosensors …

Comparison Of Treadmill Gait Between A Pediatric-Aged Individual With Syngap1-Related Intellectual Disability And A Fraternal Twin, Charles S Layne, Christopher A Malaya, David R Young, Berhard Suter, Jimmy L Holder

Duncan NRI Faculty and Staff Publications

SYNGAP1-related Intellectual Disability (SYNGAP1-ID) is a rare neurodevelopmental condition characterized by profound intellectual disability, gross motor delays, and behavioral issues. Ataxia and gait difficulties are often observed but have not yet been characterized by laboratory-based kinematic analyses. This investigation identified gait characteristics of an individual with SYNGAP1-ID and compared these with a neurotypical fraternal twin. Lower limb kinematics were collected with a 12-camera motion capture system while both participants walked on a motorized treadmill. Kinematic data were separated into strides, and stride times calculated. Sagittal plane hip, knee, and ankle joints were filtered and temporally normalized …

Evolution Of Genetic Networks For Human Creativity, I Zwir, C Del-Val, M Hintsanen, K M Cloninger, R Romero-Zaliz, A Mesa, J Arnedo, R Salas, G F Poblete, E Raitoharju, O Raitakari, L Keltikangas-Järvinen, G A De Erausquin, I Tattersall, T Lehtimäki, C R Cloninger

Staff and Researcher Publications

The genetic basis for the emergence of creativity in modern humans remains a mystery despite sequencing the genomes of chimpanzees and Neanderthals, our closest hominid relatives. Data-driven methods allowed us to uncover networks of genes distinguishing the three major systems of modern human personality and adaptability: emotional reactivity, self-control, and self-awareness. Now we have identified which of these genes are present in chimpanzees and Neanderthals. We replicated our findings in separate analyses of three high-coverage genomes of Neanderthals. We found that Neanderthals had nearly the same genes for emotional reactivity as chimpanzees, and they were intermediate between modern humans and …

Quantification Of Behavioral Deficits In Developing Mice With Dystonic Behaviors., Meike E Van Der Heijden, Jason S Gill, Alejandro G Rey Hipolito, Luis E Salazar Leon, Roy V Sillitoe

Duncan NRI Faculty and Staff Publications

Converging evidence from structural imaging studies in patients, the function of dystonia-causing genes, and the comorbidity of neuronal and behavioral defects all suggest that pediatric-onset dystonia is a neurodevelopmental disorder. However, to fully appreciate the contribution of altered development to dystonia, a mechanistic understanding of how networks become dysfunctional is required for early-onset dystonia. One current hurdle is that many dystonia animal models are ideally suited for studying adult phenotypes, as the neurodevelopmental features can be subtle or are complicated by broad developmental deficits. Furthermore, most assays that are used to measure dystonia are not suited for developing postnatal mice. …

Faces Of Pain In Dementia: Learnings From A Real-World Study Using A Technology-Enabled Pain Assessment Tool, Mustafa Atee, Kreshnik Hoti, Paola Chivers, Jeffery D. Hughes

Research outputs 2022 to 2026

Pain is common in people living with dementia (PLWD), including those with limited verbal skills. Facial expressions are key behavioral indicators of the pain experience in this group. However, there is a lack of real-world studies to report the prevalence and associations of pain-relevant facial micro-expressions in PLWD. In this observational retrospective study, pain-related facial features were studied in a sample of 3,144 PLWD [mean age 83.3 years (SD = 9.0); 59.0% female] using the Face domain of PainChek®, a point-of-care medical device application. Pain assessments were completed by 389 users from two national dementia-specific care programs and 34 Australian …

Patients’ Experiences Of A Communication Enhanced Environment Model On An Acute/Slow Stream Rehabilitation And A Rehabilitation Ward Following Stroke: A Qualitative Description Approach, Sarah D'Souza, Deborah J. Hersh, Erin Godecke, Natalie Ciccone, Heidi Janssen, Elizabeth Armstrong

Research outputs 2014 to 2021

Background

Patients in hospital following stroke express a desire to continue therapy tasks outside of treatment activities. However, they commonly describe experiences of boredom and inactivity. An enriched environment aims to provide opportunities for physical, cognitive and social activity and informed the development of a Communication Enhanced Environment (CEE) model to promote patient engagement in language activities.

Purpose

Explore patient perceptions of a CEE model, and barriers and facilitators to engagement in the model.

Methods

A qualitative description study from a larger project that implemented a CEE model into acute and rehabilitation private hospital wards in Western Australia. Semi-structured interviews …

Protocol For The Development Of The International Population Registry For Aphasia After Stroke (I-Praise), M. Ali, A. L. Ben Basat, M. Berthier, M. B. Johansson, C. Breitenstein, D. A. Cadilhac, F. Constantinidou, M. Cruice, G. Davila, M. Gandolfi, M. Gil, R. Grima, Erin Godecke, L. Jesus, L. M. Jiminez, M. Kambanaros, T. Kukkonen, A. Laska, I. Mavis, R. Mc Menamin, C. Mendez-Orellana, H. Obrig, P. Ostberg, H. Robson, K. Sage, M. Van De Sandt-Koenderman, K. Sprecht, E. Visch-Brink, E. Wehling, S. Wielaert, S. J. Wallace, L. J. Williams, M. C. Brady

Research outputs 2014 to 2021

Background: We require high-quality information on the current burden, the types of therapy and resources available, methods of delivery, care pathways and long-term outcomes for people with aphasia. Aim: To document and inform international delivery of post-stroke aphasia treatment, to optimise recovery and reintegration of people with aphasia. Methods & Procedures: Multi-centre, prospective, non-randomised, open study, employing blinded outcome assessment, where appropriate, including people with post-stroke aphasia, able to attend for 30 minutes during the initial language assessment, at first contact with a speech and language therapist for assessment of aphasia at participating sites. There is no study-mandated intervention. Assessments …

5-Ht2 Receptor Antagonism Reduces Human Motoneuron Output To Antidromic Activation But Not To Stimulation Of Corticospinal Axons, Jacob R. Thorstensen, Janet L. Taylor, Justin J. Kavanagh

Research outputs 2022 to 2026

The intrinsic electrical properties of motoneurons strongly affect motoneuron excitability to fast-acting excitatory ionotropic inputs. Serotonin (5-HT) is a neurochemical that alters the intrinsic properties of motoneurons, whereby animal models and in vitro experiments indicate that 5-HT increases motoneuron excitability by activating 5-HT2 receptors on the somato-dendritic compartment. In the current study, we examined how antagonism of the 5-HT2 receptor affects motoneuron excitability in humans. We hypothesised that motoneuron excitability would be reduced. The 5-HT2 antagonist cyproheptadine was administered to 10 healthy participants in a double-blinded, placebo-controlled, crossover trial. Electrical cervicomedullary stimulation was used to deliver a synchronised excitatory volley …

Transcranial Magnetic Stimulation To Assess Motor Neurophysiology After Acute Stroke In The United States: Feasibility, Lessons Learned, And Values For Future Research, Yi-Ling Kuo, David J. Lin, Isha Vora, Julie A. Dicarlo, Dylan J. Edwards, Teresa J. Kimberley

Research outputs 2022 to 2026

Transcranial magnetic stimulation (TMS) has been widely applied in both basic and clinical neuroscience since its introduction in 1985 . . .