In-Vitro Validation Of Intratumoral Modulation Therapy For Glioblastoma, 2022 Western University
In-Vitro Validation Of Intratumoral Modulation Therapy For Glioblastoma, Abdulla Elsaleh
Undergraduate Student Research Internships Conference
Intratumoral modulation therapy (IMT) is a novel electrotherapy used to treat brain cancer tumours using electric fields applied directly to the tumours through implanted electrodes. Previous research has validated IMT's effectiveness and provided computer-simulated optimizations for IMT electric fields. This work validates these computer optimizations in-vitro, using a PCB construct to deliver electric fields, and bioluminescence imaging to assess cell viability.
We found electric field strength to correlate with cell viability, and found that rotating (phase-shifted) electric fields did not produce significant improvements in IMT efficacy. Future work will investigate different IMT frequencies and other parameters, while providing biological replicates …
Auditory Sensory Filtering And Development In Children With Autism Spectrum Disorder, 2022 Western University
Auditory Sensory Filtering And Development In Children With Autism Spectrum Disorder, Hiruthika Ravi, Ala Seif, Ryan A. Stevenson
Undergraduate Student Research Internships Conference
Sensory filtering is the process of separating and distilling relevant sensory information from irrelevant, which in turn greatly reduces the quantity of sensory information that is fully processed and leads to significant increases in efficiency. Atypical sensory filtering can result in sensory hypo- or hypersensitivity — atypical sensory filtering and hypo/hypersensitivity have been observed in people with autism. Atypical sensory filtering contributes to canonical symptoms in Autism.
Sensory filtering can be measured in a few different ways, one of which is the Acoustic Startle Response (ASR). ASR is a reflexively produced muscular reaction to sudden auditory stimuli.
Our study aims …
Advancing The Assessment And Treatment Of Signs And Symptoms Of Parkinson Disease, 2022 Washington University School of Medicine in St. Louis
Advancing The Assessment And Treatment Of Signs And Symptoms Of Parkinson Disease, David Scott May
WUSM Theses and Dissertations – All Programs
People with PD often report signs and symptoms that negatively impact quality of life. Among these are balance difficulties, impaired gait, and FOG. New treatment and assessment strategies for these signs and symptoms are needed, as current techniques are limited. While new treatment and assessment strategies continue to emerge, gaps in knowledge persist. Deep brain stimulation (DBS) has been utilized in many people with PD throughout the 21st century, but it is unknown specifically how subthalamic nucleus deep brain stimulation (STN-DBS) affects balance. Alternative treatment strategies, such as a dental mouthpiece, have also been proposed. While dental mouthpieces have shown …
Characterization And Comparison Of Human Glioblastoma Models, 2022 University of Kentucky
Characterization And Comparison Of Human Glioblastoma Models, Julia A. Schulz, Louis T. Rogers, Richard J. Kryscio, Anika M. S. Hartz, Björn Bauer
Sanders-Brown Center on Aging Faculty Publications
Abstract
Glioblastoma (GBM) is one of the deadliest cancers. Treatment options are limited, and median patient survival is only several months. Translation of new therapies is hindered by a lack of GBM models that fully recapitulate disease heterogeneity. Here, we characterize two human GBM models (U87-luc2, U251-RedFLuc). In vitro, both cell lines express similar levels of luciferase and show comparable sensitivity to temozolomide and lapatinib exposure. In vivo, however, the two GBM models recapitulate diferent aspects of the disease. U87-luc2 cells quickly grow into large, well-demarcated tumors; U251-RedFLuc cells form small, highly invasive tumors. Using a new method to assess …
Cognitive Testing For Sport Concussion: The Immediate Post-Concussion Assessment And Cognitive Testing (Impact), 2022 University of Nevada, Las Vegas
Cognitive Testing For Sport Concussion: The Immediate Post-Concussion Assessment And Cognitive Testing (Impact), Julia E. Maietta
UNLV Theses, Dissertations, Professional Papers, and Capstones
Sport concussion is among the most common injuries for an athlete to experience during sport participation. Because of the complex pathophysiological process that affects the brain during and after concussion, symptoms can be heterogeneous in presence and severity. Although most acute symptoms (e.g., headache, slowed processing speed, loss of consciousness, irritability, depression, anxiety) resolve within seven to 10 days for most athletes, there is evidence that higher initial symptom burden and other genetically based differences can lead to longer symptom duration and complicated recovery post-concussion. Because structural changes that commonly occur as a result of concussion (e.g., diffuse axonal injury) …
Synergistic Neuroprotection By A Paf Antagonist Plus A Docosanoid In Experimental Ischemic Stroke: Dose-Response And Therapeutic Window, 2022 LSU Health Sciences Center - New Orleans
Synergistic Neuroprotection By A Paf Antagonist Plus A Docosanoid In Experimental Ischemic Stroke: Dose-Response And Therapeutic Window, Madigan M. Reid, Andre Obenaus, Pranab K. Mukherjee, Larissa Khoutorova, Cassia R. Roque, Nicos A. Petasis, Reinaldo B. Oria, Ludmila Belayev, Nicolas G. Bazan
School of Graduate Studies Faculty Publications
Objective: We tested the hypothesis that blocking pro-inflammatory platelet-activating factor receptor (PAFR) with LAU-0901 (LAU) plus administering a selected docosanoid, aspirin-triggered neuroprotectin D1 (AT-NPD1), which activates cell-survival pathways after middle cerebral artery occlusion (MCAo), would lead to neurological recovery. Dose-response and therapeutic window were investigated. Materials and methods: Male SD rats were subjected to 2 hours of MCAo. Behavior testing (days 1-7) and ex vivo MRI on day 7 were conducted. In dose-response, rats were treated with LAU (45 and 60 mg/kg; IP), AT-NPD1 (111, 222, 333 µg/kg; IV), LAU+AT-NPD1 (LAU at 3 hours and AT-NPD1 at 3.15 hours) or …
Vasopressin Resets The Central Circadian Clock In A Manner Influenced By Sex And Vasoactive Intestinal Polypeptide Signaling, 2022 Marquette University
Vasopressin Resets The Central Circadian Clock In A Manner Influenced By Sex And Vasoactive Intestinal Polypeptide Signaling, Kayla E. Rohr, Thomas Inda, Jennifer A. Evans
Biomedical Sciences Faculty Research and Publications
Background/Aims: Circadian rhythms in behavior and physiology are programmed by the suprachiasmatic nucleus (SCN) of the hypothalamus. A subset of SCN neurons produce the neuropeptide arginine vasopressin (AVP), but it remains unclear whether AVP signaling influences the SCN clock directly.
Methods: Here, we test that AVP signaling acting through V1A and V1B receptors influences molecular rhythms in SCN neurons. V1 receptor agonists were applied ex vivo to PERIOD2::LUCIFERASE SCN slices, allowing for real-time monitoring of changes in molecular clock function.
Results: V1A/B agonists reset the phase of the SCN molecular clock in a time-dependent manner, with larger magnitude responses by …
Editorial: Glia-Mediated Neurotoxicity: Uncovering The Molecular Mechanisms, 2022 Thomas Jefferson University
Editorial: Glia-Mediated Neurotoxicity: Uncovering The Molecular Mechanisms, Amit K Srivastava, Barbara Lukomska, Lorraine Iacovitti
Farber Institute for Neuroscience Faculty Papers
No abstract provided.
Cryo-Em Structure Of The Human Kv3.1 Channel Reveals Gating Control By The Cytoplasmic T1 Domain, 2022 University of Oxford
Cryo-Em Structure Of The Human Kv3.1 Channel Reveals Gating Control By The Cytoplasmic T1 Domain, Gamma Chi, Qiansheng Liang, Akshay Sridhar, John B Cowgill, Kasim Sader, Mazdak Radjainia, Pu Qian, Pablo Castro-Hartmann, Shayla Venkaya, Nanki Kaur Singh, Gavin Mckinley, Alejandra Fernandez-Cid, Shubhashish M M Mukhopadhyay, Nicola A Burgess-Brown, Lucie Delemotte, Manuel Covarrubias, Katharina L Dürr
Department of Neuroscience Faculty Papers
Kv3 channels have distinctive gating kinetics tailored for rapid repolarization in fast-spiking neurons. Malfunction of this process due to genetic variants in the KCNC1 gene causes severe epileptic disorders, yet the structural determinants for the unusual gating properties remain elusive. Here, we present cryo-electron microscopy structures of the human Kv3.1a channel, revealing a unique arrangement of the cytoplasmic tetramerization domain T1 which facilitates interactions with C-terminal axonal targeting motif and key components of the gating machinery. Additional interactions between S1/S2 linker and turret domain strengthen the interface between voltage sensor and pore domain. Supported by molecular dynamics simulations, electrophysiological and …
Brain-Wide Analysis Of The Supraspinal Connectome Reveals Anatomical Correlates To Functional Recovery After Spinal Injury, 2022 Marquette University
Brain-Wide Analysis Of The Supraspinal Connectome Reveals Anatomical Correlates To Functional Recovery After Spinal Injury, Zimei Wang, Adam Romanski, Vatsal Mehra, Yunfang Wang, Matthew Brannigan, Benjamin C. Campbell, Gregory A. Petsko, Pantelis Tsoulfas, Murray G. Blackmore
Biomedical Sciences Faculty Research and Publications
The supraspinal connectome is essential for normal behavior and homeostasis and consists of numerous sensory, motor, and autonomic projections from brain to spinal cord. Study of supraspinal control and its restoration after damage has focused mostly on a handful of major populations that carry motor commands, with only limited consideration of dozens more that provide autonomic or crucial motor modulation. Here, we assemble an experimental workflow to rapidly profile the entire supraspinal mesoconnectome in adult mice and disseminate the output in a web-based resource. Optimized viral labeling, 3D imaging, and registration to a mouse digital neuroanatomical atlas assigned tens of …
An Il1rl1 Genetic Variant Lowers Soluble St2 Levels And The Risk Effects Of Apoe-Ε4 In Female Patients With Alzheimer’S Disease, 2022 The Hong Kong University of Science and Technology, China
An Il1rl1 Genetic Variant Lowers Soluble St2 Levels And The Risk Effects Of Apoe-Ε4 In Female Patients With Alzheimer’S Disease, Yuanbing Jiang, Xiaopu Zhou, Hui Yi Wong, Li Ouyang, Fanny C. F. Ip, Vicky M. N. Chau, Shun-Fat Lau, Wei Wu, Daniel Y. K. Wong, Heukjin Seo, Wing-Yu Fu, Nicole C. H. Lai, Yuewen Chen, Alzheimer’S Disease Neuroimaging Initiative, Charles D. Smith, Gregory A. Jicha, Peter A. Hardy, Partha Sinha, Elizabeth Oates, Gary Conrad
Sanders-Brown Center on Aging Faculty Publications
Changes in the levels of circulating proteins are associated with Alzheimer’s disease (AD), whereas their pathogenic roles in AD are unclear. Here, we identified soluble ST2 (sST2), a decoy receptor of interleukin-33–ST2 signaling, as a new disease-causing factor in AD. Increased circulating sST2 level is associated with more severe pathological changes in female individuals with AD. Genome-wide association analysis and CRISPR–Cas9 genome editing identified rs1921622, a genetic variant in an enhancer element of IL1RL1, which downregulates gene and protein levels of sST2. Mendelian randomization analysis using genetic variants, including rs1921622, demonstrated that decreased sST2 levels lower AD …
Γ-Secretase Promotes Drosophila Postsynaptic Development Through The Cleavage Of A Wnt Receptor, 2022 Thomas Jefferson University
Γ-Secretase Promotes Drosophila Postsynaptic Development Through The Cleavage Of A Wnt Receptor, Lucas J Restrepo, Alison T Depew, Elizabeth R Moese, Stephen R Tymanskyj, Michael J Parisi, Michael A Aimino, Juan Carlos Duhart, Hong Fei, Timothy J Mosca
Farber Institute for Neuroscience Faculty Papers
Developing synapses mature through the recruitment of specific proteins that stabilize presynaptic and postsynaptic structure and function. Wnt ligands signaling via Frizzled (Fz) receptors play many crucial roles in neuronal and synaptic development, but whether and how Wnt and Fz influence synaptic maturation is incompletely understood. Here, we show that Fz2 receptor cleavage via the γ-secretase complex is required for postsynaptic development and maturation. In the absence of γ-secretase, Drosophila neuromuscular synapses fail to recruit postsynaptic scaffolding and cytoskeletal proteins, leading to behavioral deficits. Introducing presenilin mutations linked to familial early-onset Alzheimer's disease into flies leads to synaptic maturation phenotypes …
Biallelic Variants In Wars1 Cause A Highly Variable Neurodevelopmental Syndrome And Implicate A Critical Exon For Normal Auditory Function, 2022 Oklahoma Medical Research Foundation
Biallelic Variants In Wars1 Cause A Highly Variable Neurodevelopmental Syndrome And Implicate A Critical Exon For Normal Auditory Function, Sheng Jia Lin, Barbara Vona, Hillary M. Porter, Mahmoud Izadi, Kevin Huang, Yves Lacassie, Jill A. Rosenfeld, Saadullah Khan, Cassidy Petree, Tayyiba A. Ali, Nazif Muhammad, Sher A. Khan, Noor Muhammad, Pengfei Liu, Marie Louise Haymon, Franz Rüschendorf, Il Keun Kong, Linda Schnapp, Natasha Shur, Lynn Chorich, Lawrence Layman, Thomas Haaf, Ehsan Pourkarimi, Hyung Goo Kim, Gaurav K. Varshney
School of Medicine Faculty Publications
Aminoacyl-tRNA synthetases (ARSs) are essential enzymes for faithful assignment of amino acids to their cognate tRNA. Variants in ARS genes are frequently associated with clinically heterogeneous phenotypes in humans and follow both autosomal dominant or recessive inheritance patterns in many instances. Variants in tryptophanyl-tRNA synthetase 1 (WARS1) cause autosomal dominantly inherited distal hereditary motor neuropathy and Charcot-Marie-Tooth disease. Presently, only one family with biallelic WARS1 variants has been described. We present three affected individuals from two families with biallelic variants (p.Met1? and p.(Asp419Asn)) in WARS1, showing varying severities of developmental delay and intellectual disability. Hearing impairment and microcephaly, as well …
Exogenous Short Chain Fatty Acid Effects In App/Ps1 Mice, 2022 University of Kentucky
Exogenous Short Chain Fatty Acid Effects In App/Ps1 Mice, Diana J. Zajac, Benjamin C. Shaw, David J. Braun, Stefan J. Green, Joshua M. Morganti, Steven Estus
Sanders-Brown Center on Aging Faculty Publications
Elucidating the impact of the gut microbiome on Alzheimer’s Disease (AD) is an area of intense interest. Short chain fatty acids (SCFAs) are major microbiota metabolites that have been implicated as a mediator of gut microbiome effects in the brain. Here, we tested the effects of SCFA-treated water vs. saline-treated water on APPswe/PSEN1dE9 mice maintained under standard laboratory conditions. Mice were treated with SCFAs from five months of age until ten months of age, when they were evaluated for microbiome profile, impaired spatial memory as evaluated with the radial arm water maze, astrocyte activation as measured by Gfap expression and …
Sex Differences In The Genetic Architecture Of Cognitive Resilience To Alzheimer’S Disease, 2022 Vanderbilt University Medical Center
Sex Differences In The Genetic Architecture Of Cognitive Resilience To Alzheimer’S Disease, Jaclyn M. Eissman, Logan Dumitrescu, Emily R. Mahoney, Alexandra N. Smith, Shubhabrata Mukherjee, Michael L. Lee, Phoebe Scollard, Seo Eun Choi, William S. Bush, Corinne D. Engelman, Qiongshi Lu, David W. Fardo, Emily H. Trittschuh, Jesse Mez, Catherine C. Kaczorowski, Hector Hernandez Saucedo, Keith F. Widaman, Rachel F. Buckley, Michael J. Properzi, Elizabeth C. Mormino, Hyun Sik Yang, Theresa M. Harrison, Trey Hedden, Kwangsik Nho, Shea J. Andrews, Douglas Tommet, Niran Hadad, R. Elizabeth Sanders, Douglas M. Ruderfer, Katherine A. Gifford, Xiaoyuan Zhong, Neha S. Raghavan, Badri Vardarajan, Margaret A. Pericak-Vance, Lindsay A. Farrer, Li San Wang, Carlos Cruchaga, Gerard D. Schellenberg, Nancy J. Cox, Jonathan L. Haines, C. Dirk Keene, Andrew J. Saykin, Eric B. Larson, Reisa A. Sperling, Richard Mayeux, Michael L. Cuccaro, David A. Bennett, Julie A. Schneider, Paul K. Crane, Angela L. Jefferson, Timothy J. Hohman
Sanders-Brown Center on Aging Faculty Publications
Approximately 30% of elderly adults are cognitively unimpaired at time of death despite the presence of Alzheimer's disease neuropathology at autopsy. Studying individuals who are resilient to the cognitive consequences of Alzheimer's disease neuropathology may uncover novel therapeutic targets to treat Alzheimer's disease. It is well established that there are sex differences in response to Alzheimer's disease pathology, and growing evidence suggests that genetic factors may contribute to these differences. Taken together, we sought to elucidate sex-specific genetic drivers of resilience.
We extended our recent large scale genomic analysis of resilience in which we harmonized cognitive data across four cohorts …
Enlarged Perivascular Spaces Are Negatively Associated With Montreal Cognitive Assessment Scores In Older Adults, 2022 University of Kentucky
Enlarged Perivascular Spaces Are Negatively Associated With Montreal Cognitive Assessment Scores In Older Adults, Timothy J. Libecap, Valentinos Zachariou, Christopher E. Bauer, Donna M. Wilcock, Gregory A. Jicha, Flavius D. Raslau, Brian T. Gold
Sanders-Brown Center on Aging Faculty Publications
Emerging evidence suggests that enlarged perivascular spaces (ePVS) may be a clinically significant neuroimaging marker of global cognitive function related to cerebral small vessel disease (cSVD). We tested this possibility by assessing the relationship between ePVS and both a standardized measure of global cognitive function, the Montreal Cognitive Assessment (MoCA), and an established marker of cSVD, white matter hyperintensity volume (WMH) volume. One hundred and eleven community-dwelling older adults (56–86) underwent neuroimaging and MoCA testing. Quantification of region-specific ePVS burden was performed using a previously validated visual rating method and WMH volumes were computed using the standard ADNI pipeline. Separate …
Impact Of The Covid-19 Pandemic On Daily Life, Mood, And Behavior Of Adults With Down Syndrome, 2022 University of Wisconsin-Madison
Impact Of The Covid-19 Pandemic On Daily Life, Mood, And Behavior Of Adults With Down Syndrome, Sigan L. Hartley, Victoria Fleming, Brianna Piro-Gambetti, Annie Cohen, Beau M. Ances, Michael A. Yassa, Adam M. Brickman, Benjamin L. Handen, Elizabeth Head, Mark Mapstone, Bradley T. Christian, Ira T. Lott, Eric Doran, Shahid Zaman, Sharon Krinsky-Mchale, Frederick A. Schmitt, Christy L. Hom, Nicole Schupf
Sanders-Brown Center on Aging Faculty Publications
Background: The Down syndrome population has been disproportionately affected by Coronavirus 2019 (COVID-19) in terms of experiencing severe illness and death. Societal efforts to curb the spread of COVID-19 may also have taken a heavy toll on the daily lives of individuals with Down syndrome.
Objective/hypothesis: The goal of the study was to understand how the COVID-19 pandemic has altered daily life (including residence, employment, and participation in adult disability day programs) and influenced the mood and behavior of adults with Down syndrome.
Methods: Between September 2020 and February 2021, caregivers of 171 adults with Down syndrome (aged …
Concurrent Exposure To (Acute Intermittent) Hypoxia And Hypercapnia: A Promising Therapeutic Cocktail For Neuroplasticity?, 2022 Edith Cowan University
Concurrent Exposure To (Acute Intermittent) Hypoxia And Hypercapnia: A Promising Therapeutic Cocktail For Neuroplasticity?, Ricardo N. O. Mesquita
Research outputs 2022 to 2026
Pioneering experiments revealed that intermittent stimulation of afferent neurons from the carotid bodies elicits long-lasting increased activity of respiratory nerves, a phenomenon known as respiratory long-term facilitation (LTF). Initially observed with episodic electrical stimulation of the carotid sinus nerve, this phenomenon was then extensively demonstrated in rodent experiments via protocols of brief, episodic exposures to periods of hypoxia (i.e. acute intermittent hypoxia; AIH). Then, the realization that AIH could be used as a therapeutic modality to induce neuroplasticity and restore both respiratory and non-respiratory motor function in rats with spinal cord injuries (SCI) motivated translation to human studies. AIH has …
Using Noise For The Better: The Effects Of Transcranial Random Noise Stimulation On The Brain And Behavior, 2022 Edith Cowan University
Using Noise For The Better: The Effects Of Transcranial Random Noise Stimulation On The Brain And Behavior, Onno Van Der Groen, Weronika Potok, Nicole Wenderoth, Grace Edwards, Jason B. Mattingley, Dylan Edwards
Research outputs 2022 to 2026
NEUROSCI BIOBEHAV REV X (X) XXX-XXX 2021.- Transcranial random noise stimulation (tRNS) is a non-invasive electrical brain stimulation method that is increasingly employed in studies of human brain function and behavior, in health and disease. tRNS is effective in modulating perception acutely and can improve learning. By contrast, its effectiveness for modulating higher cognitive processes is variable. Prolonged stimulation with tRNS, either as one longer application, or multiple shorter applications, may engage plasticity mechanisms that can result in long-term benefits. Here we provide an overview of the current understanding of the effects of tRNS on the brain and behavior and …
The Role Of Microglia In Neuroinflammation Of The Spinal Cord After Peripheral Nerve Injury, 2022 Wright State University
The Role Of Microglia In Neuroinflammation Of The Spinal Cord After Peripheral Nerve Injury, Tana S. Pottorf, Travis M. Rotterman, William M. Mccallum, Zoë A. Haley-Johnson, Francisco J. Alvarez
Neuroscience, Cell Biology & Physiology Faculty Publications
Peripheral nerve injuries induce a pronounced immune reaction within the spinal cord, largely governed by microglia activation in both the dorsal and ventral horns. The mechanisms of activation and response of microglia are diverse depending on the location within the spinal cord, type, severity, and proximity of injury, as well as the age and species of the organism. Thanks to recent advancements in neuro-immune research techniques, such as single-cell transcriptomics, novel genetic mouse models, and live imaging, a vast amount of literature has come to light regarding the mechanisms of microglial activation and alluding to the function …