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Nervous System Diseases Commons

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Articles 1 - 30 of 73

Full-Text Articles in Nervous System Diseases

Apigenin Alleviates Autistic-Like Stereotyped Repetitive Behaviors And Mitigates Brain Oxidative Stress In Mice, Petrilla Jayaprakash, Dmytro Isaev, Keun-Hang Susan Yang, Rami Beiram, Murat Oz, Bassem Sadek Apr 2024

Apigenin Alleviates Autistic-Like Stereotyped Repetitive Behaviors And Mitigates Brain Oxidative Stress In Mice, Petrilla Jayaprakash, Dmytro Isaev, Keun-Hang Susan Yang, Rami Beiram, Murat Oz, Bassem Sadek

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Studying the involvement of nicotinic acetylcholine receptors (nAChRs), specifically α7-nAChRs, in neuropsychiatric brain disorders such as autism spectrum disorder (ASD) has gained a growing interest. The flavonoid apigenin (APG) has been confirmed in its pharmacological action as a positive allosteric modulator of α7-nAChRs. However, there is no research describing the pharmacological potential of APG in ASD. The aim of this study was to evaluate the effects of the subchronic systemic treatment of APG (10–30 mg/kg) on ASD-like repetitive and compulsive-like behaviors and oxidative stress status in the hippocampus and cerebellum in BTBR mice, utilizing the reference drug aripiprazole (ARP, 1 …


Modulation Of Hippocampal Protein Expression By A Brain Penetrant Biologic Tnf-Α Inhibitor In The 3xtg Alzheimer’S Disease Mice, Nataraj Jagadeesan, G. Chuli Roules, Devaraj V. Chandrashekar, Joshua Yang, Sanjana Kolluru, Rachita K. Sumbria Mar 2024

Modulation Of Hippocampal Protein Expression By A Brain Penetrant Biologic Tnf-Α Inhibitor In The 3xtg Alzheimer’S Disease Mice, Nataraj Jagadeesan, G. Chuli Roules, Devaraj V. Chandrashekar, Joshua Yang, Sanjana Kolluru, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Background

Biologic TNF-α inhibitors (bTNFIs) can block cerebral TNF-α in Alzheimer’s disease (AD) if these macromolecules can cross the blood–brain barrier (BBB). Thus, a model bTNFI, the extracellular domain of type II TNF-α receptor (TNFR), which can bind to and sequester TNF-α, was fused with a mouse transferrin receptor antibody (TfRMAb) to enable brain delivery via BBB TfR-mediated transcytosis. Previously, we found TfRMAb-TNFR to be protective in a mouse model of amyloidosis (APP/PS1) and tauopathy (PS19), and herein we investigated its effects in mice that combine both amyloidosis and tauopathy (3xTg-AD).

Methods

Eight-month-old female 3xTg-AD mice were injected intraperitoneally with …


Oxidative Stress And Ion Channels In Neurodegenerative Diseases, Razan Orfali, Adnan Z. Alwatban, Rawan S. Orfali, Liz Lau, Noble Chea, Abdullah M. Alotaibi, Young-Woo Nam, Miao Zhang Jan 2024

Oxidative Stress And Ion Channels In Neurodegenerative Diseases, Razan Orfali, Adnan Z. Alwatban, Rawan S. Orfali, Liz Lau, Noble Chea, Abdullah M. Alotaibi, Young-Woo Nam, Miao Zhang

Pharmacy Faculty Articles and Research

Numerous neurodegenerative diseases result from altered ion channel function and mutations. The intracellular redox status can significantly alter the gating characteristics of ion channels. Abundant neurodegenerative diseases associated with oxidative stress have been documented, including Parkinson’s, Alzheimer’s, spinocerebellar ataxia, amyotrophic lateral sclerosis, and Huntington’s disease. Reactive oxygen and nitrogen species compounds trigger posttranslational alterations that target specific sites within the subunits responsible for channel assembly. These alterations include the adjustment of cysteine residues through redox reactions induced by reactive oxygen species (ROS), nitration, and S-nitrosylation assisted by nitric oxide of tyrosine residues through peroxynitrite. Several ion channels have been directly …


Multi-Site Identification And Generalization Of Clusters Of Walking Behaviors In Individuals With Chronic Stroke And Neurotypical Controls, Natalia Sánchez, Nicolas Schweighofer, Sara J. Mulroy, Ryan T. Roemmich, Trisha M. Keshar, Gelsy Torres-Oviedo, Beth E. Fisher, James M. Finley, Carolee J. Winstein Nov 2023

Multi-Site Identification And Generalization Of Clusters Of Walking Behaviors In Individuals With Chronic Stroke And Neurotypical Controls, Natalia Sánchez, Nicolas Schweighofer, Sara J. Mulroy, Ryan T. Roemmich, Trisha M. Keshar, Gelsy Torres-Oviedo, Beth E. Fisher, James M. Finley, Carolee J. Winstein

Physical Therapy Faculty Articles and Research

Background

Walking patterns in stroke survivors are highly heterogeneous, which poses a challenge in systematizing treatment prescriptions for walking rehabilitation interventions.

Objectives

We used bilateral spatiotemporal and force data during walking to create a multi-site research sample to: (1) identify clusters of walking behaviors in people post-stroke and neurotypical controls and (2) determine the generalizability of these walking clusters across different research sites. We hypothesized that participants post-stroke will have different walking impairments resulting in different clusters of walking behaviors, which are also different from control participants.

Methods

We gathered data from 81 post-stroke participants across 4 research sites and …


Erythrocyte–Brain Endothelial Interactions Induce Microglial Responses And Cerebral Microhemorrhages In Vivo, Hai Zhang, Rachita K. Sumbria, Rudy Chang, Jiahong Sun, David H. Cribbs, Todd C. Holmes, Mark J. Fisher, Xiangmin Xu Nov 2023

Erythrocyte–Brain Endothelial Interactions Induce Microglial Responses And Cerebral Microhemorrhages In Vivo, Hai Zhang, Rachita K. Sumbria, Rudy Chang, Jiahong Sun, David H. Cribbs, Todd C. Holmes, Mark J. Fisher, Xiangmin Xu

Pharmacy Faculty Articles and Research

Background

Cerebral microhemorrhages (CMH) are associated with stroke, cognitive decline, and normal aging. Our previous study shows that the interaction between oxidatively stressed red blood cells (RBC) and cerebral endothelium may underlie CMH development. However, the real-time examination of altered RBC–brain endothelial interactions in vivo, and their relationship with clearance of stalled RBC, microglial responses, and CMH development, has not been reported.

Methods

RBC were oxidatively stressed using tert-butylhydroperoxide (t-BHP), fluorescently labeled and injected into adult Tie2-GFP mice. In vivo two-photon imaging and ex vivo confocal microscopy were used to evaluate the temporal profile of RBC–brain endothelial interactions associated with …


Tolfenamic Acid Derivatives: A New Class Of Transcriptional Modulators With Potential Therapeutic Applications For Alzheimer’S Disease And Related Disorders, Juanetta Hill, Karim E. Shalaby, Syed W. Bihaqi, Bothaina H. Alansi, Benjamin Barlock, Keykavous Parang, Richard Thompson, Khalid Ourarhni, Nasser H. Zawia Oct 2023

Tolfenamic Acid Derivatives: A New Class Of Transcriptional Modulators With Potential Therapeutic Applications For Alzheimer’S Disease And Related Disorders, Juanetta Hill, Karim E. Shalaby, Syed W. Bihaqi, Bothaina H. Alansi, Benjamin Barlock, Keykavous Parang, Richard Thompson, Khalid Ourarhni, Nasser H. Zawia

Pharmacy Faculty Articles and Research

The field of Alzheimer’s disease (AD) has witnessed recent breakthroughs in the development of disease-modifying biologics and diagnostic markers. While immunotherapeutic interventions have provided much-awaited solutions, nucleic acid-based tools represent other avenues of intervention; however, these approaches are costly and invasive, and they have serious side effects. Previously, we have shown in AD animal models that tolfenamic acid (TA) can lower the expression of AD-related genes and their products and subsequently reduce pathological burden and improve cognition. Using TA as a scaffold and the zinc finger domain of SP1 as a pharmacophore, we developed safer and more potent brain-penetrating analogs …


Alcohol As A Modifiable Risk Factor For Alzheimer’S Disease—Evidence From Experimental Studies, Devaraj V. Chandrashekar, Ross A. Steinberg, Derick Han, Rachita K. Sumbria May 2023

Alcohol As A Modifiable Risk Factor For Alzheimer’S Disease—Evidence From Experimental Studies, Devaraj V. Chandrashekar, Ross A. Steinberg, Derick Han, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by cognitive impairment and memory loss. Epidemiological evidence suggests that heavy alcohol consumption aggravates AD pathology, whereas low alcohol intake may be protective. However, these observations have been inconsistent, and because of methodological discrepancies, the findings remain controversial. Alcohol-feeding studies in AD mice support the notion that high alcohol intake promotes AD, while also hinting that low alcohol doses may be protective against AD. Chronic alcohol feeding to AD mice that delivers alcohol doses sufficient to cause liver injury largely promotes and accelerates AD pathology. The mechanisms by which alcohol can …


Identifying The Neural Correlates Of Anticipatory Postural Control: A Novel Fmri Paradigm, Jo Armour Smith, Rongwen Tain, Kelli G. Sharp, Laura M. Glynn, Linda R. Van Dillen, Korinne Henslee, Jesse V. Jacobs, Steven C. Cramer May 2023

Identifying The Neural Correlates Of Anticipatory Postural Control: A Novel Fmri Paradigm, Jo Armour Smith, Rongwen Tain, Kelli G. Sharp, Laura M. Glynn, Linda R. Van Dillen, Korinne Henslee, Jesse V. Jacobs, Steven C. Cramer

Physical Therapy Faculty Articles and Research

Altered postural control in the trunk/hip musculature is a characteristic of multiple neurological and musculoskeletal conditions. Previously it was not possible to determine if altered cortical and subcortical sensorimotor brain activation underlies impairments in postural control. This study used a novel fMRI-compatible paradigm to identify the brain activation associated with postural control in the trunk and hip musculature. BOLD fMRI imaging was conducted as participants performed two versions of a lower limb task involving lifting the left leg to touch the foot to a target. For the supported leg raise (SLR) the leg is raised from the knee while the …


Mindfulness Meditation As A Complementary Therapy For Chronic Migraines, Isaac Min, Manjari Murali May 2023

Mindfulness Meditation As A Complementary Therapy For Chronic Migraines, Isaac Min, Manjari Murali

Student Scholar Symposium Abstracts and Posters

Migraine headaches, the most common neurological disease across all age groups, affect over one billion individuals worldwide, with symptoms ranging from moderate to severe. Migraines differ in intensity and are accompanied by secondary symptoms, such as neck pain, nausea, and vomiting. Current efforts in treating migraines focus on preventative drug therapy to reduce the frequency of migraine attacks. Although mindfulness-based approaches such as MBSR may serve as an alternative method of reducing the severity of migraine attacks, studies investigating the efficacy of MBSR are limited.

A meta-analysis provides insights into the pathogenesis of migraines through the identification of three genes …


The Effects Of A Blood–Brain Barrier Penetrating Erythropoietin In A Mouse Model Of Tauopathy, Joshua Yang, Weijun Ou, Nataraj Jagadeesan, Juste Simanauskaite, Jiahong Sun, Demi M. Castellanos, David H. Cribbs, Rachita K. Sumbria Apr 2023

The Effects Of A Blood–Brain Barrier Penetrating Erythropoietin In A Mouse Model Of Tauopathy, Joshua Yang, Weijun Ou, Nataraj Jagadeesan, Juste Simanauskaite, Jiahong Sun, Demi M. Castellanos, David H. Cribbs, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Erythropoietin (EPO), a hematopoietic neurotrophin, is a potential therapeutic for Alzheimer’s disease (AD) but has limited blood–brain barrier (BBB) permeability. EPO fused to a chimeric transferrin receptor monoclonal antibody (cTfRMAb) enters the brain via TfR-mediated transcytosis across the BBB. We previously showed that cTfRMAb-EPO is protective in a mouse model of amyloidosis, but its effects on tauopathy are not known. Given that amyloid and tau pathology are characteristics of AD, the effects of cTfRMAb-EPO were studied in a tauopathy mouse model (PS19). Six-month-old PS19 mice were injected intraperitoneally with either saline (PS19-Saline; n = 9) or cTfRMAb-EPO (PS19-cTfRMAb-EPO, 10 mg/kg; …


Brain Volume, Energy Balance, And Cardiovascular Health In Two Nonindustrial South American Populations, Hillard Kaplan, Paul L. Hooper, Margaret Gatz, Wendy J. Mack, E. Meng Law, Helena C. Chui, M. Linda Sutherland, James D. Sutherland, Christopher J. Rowan, L. Samuel Wann, Adel H. Allam, Randall C. Thompson, David E. Michalik, Guido Lombardi, Michael I. Miyamoto, Daniel Eid Rodriguez, Juan Copajira Adrian, Raul Quispe Gutierrez, Bret A. Beheim, Daniel K. Cummings, Edmond Seabright, Sarah Alami, Angela R. Garcia, Kenneth Buetow, Gregory S. Thomas, Caleb E. Finch, Jonathan Stieglitz, Benjamin C. Trumble, Michael D. Gurven, Andrei Irimia Mar 2023

Brain Volume, Energy Balance, And Cardiovascular Health In Two Nonindustrial South American Populations, Hillard Kaplan, Paul L. Hooper, Margaret Gatz, Wendy J. Mack, E. Meng Law, Helena C. Chui, M. Linda Sutherland, James D. Sutherland, Christopher J. Rowan, L. Samuel Wann, Adel H. Allam, Randall C. Thompson, David E. Michalik, Guido Lombardi, Michael I. Miyamoto, Daniel Eid Rodriguez, Juan Copajira Adrian, Raul Quispe Gutierrez, Bret A. Beheim, Daniel K. Cummings, Edmond Seabright, Sarah Alami, Angela R. Garcia, Kenneth Buetow, Gregory S. Thomas, Caleb E. Finch, Jonathan Stieglitz, Benjamin C. Trumble, Michael D. Gurven, Andrei Irimia

ESI Publications

Little is known about brain aging or dementia in nonindustrialized environments that are similar to how humans lived throughout evolutionary history. This paper examines brain volume (BV) in middle and old age among two indigenous South American populations, the Tsimane and Moseten, whose lifestyles and environments diverge from those in high-income nations. With a sample of 1,165 individuals aged 40 to 94, we analyze population differences in cross-sectional rates of decline in BV with age. We also assess the relationships of BV with energy biomarkers and arterial disease and compare them against findings in industrialized contexts. The analyses test three …


Varied Performance Of Picture Description Task As A Screening Tool Across Mci Subtypes, Joan A. Mefford, Zilong Zhao, Leah Heilier, Man Xu, Guifeng Zhou, Rachel Mace, Kelly L. Sloane, Shannon M. Sheppard, Shenly Glenn Mar 2023

Varied Performance Of Picture Description Task As A Screening Tool Across Mci Subtypes, Joan A. Mefford, Zilong Zhao, Leah Heilier, Man Xu, Guifeng Zhou, Rachel Mace, Kelly L. Sloane, Shannon M. Sheppard, Shenly Glenn

Communication Sciences and Disorders Faculty Articles and Research

A picture description task is a component of Miro Health’s platform for self-administration of neurobehavioral assessments. Picture description has been used as a screening tool for identification of individuals with Alzheimer’s disease and mild cognitive impairment (MCI), but currently requires in-person administration and scoring by someone with access to and familiarity with a scoring rubric. The Miro Health implementation allows broader use of this assessment through self-administration and automated processing, analysis, and scoring to deliver clinically useful quantifications of the users’ speech production, vocal characteristics, and language. Picture description responses were collected from 62 healthy controls (HC), and 33 participants …


Chronic Kidney Disease Promotes Cerebral Microhemorrhage Formation, Chuo Fang, Wei Ling Lau, Jiahong Sun, Rudy Chang, Adrian Vallejo, Donghy Lee, Jihua Liu, Han Liu, Yu-Han Hung, Yitong Zhao, Annlia Paganini-Hill, Rachita K. Sumbria, David H. Cribbs, Mark J. Fisher Feb 2023

Chronic Kidney Disease Promotes Cerebral Microhemorrhage Formation, Chuo Fang, Wei Ling Lau, Jiahong Sun, Rudy Chang, Adrian Vallejo, Donghy Lee, Jihua Liu, Han Liu, Yu-Han Hung, Yitong Zhao, Annlia Paganini-Hill, Rachita K. Sumbria, David H. Cribbs, Mark J. Fisher

Pharmacy Faculty Articles and Research

Background

Chronic kidney disease (CKD) is increasingly recognized as a stroke risk factor, but its exact relationship with cerebrovascular disease is not well-understood. We investigated the development of cerebral small vessel disease using in vivo and in vitro models of CKD.

Methods

CKD was produced in aged C57BL/6J mice using an adenine-induced tubulointerstitial nephritis model. We analyzed brain histology using Prussian blue staining to examine formation of cerebral microhemorrhage (CMH), the hemorrhagic component of small vessel disease and the neuropathological substrate of MRI-demonstrable cerebral microbleeds. In cell culture studies, we examined effects of serum from healthy or CKD patients and …


Identifying Voice-Based Digital Biomarkers Of Parkinson's Disease, Rachelle Beshay, Madison Gill, Michael Shiraishi, Rahul Soangra Nov 2022

Identifying Voice-Based Digital Biomarkers Of Parkinson's Disease, Rachelle Beshay, Madison Gill, Michael Shiraishi, Rahul Soangra

Student Scholar Symposium Abstracts and Posters

Introduction: Parkinson's disease is a disorder in the central nervous system that causes tremors, abnormal gait and balance, and muscle rigidity due to loss of function in parts of the brain. Traditionally, Parkinson's is identified by the physical symptoms seen in a patient's gait and motor skills, but irregular speech patterns (hypokinetic dysarthria) is one of the first symptoms to be derived from the disease. Objective: The goal of this ongoing study is to use Mel Frequency Centrum Coefficients (MFCC), to diagnose Parkinson's in the early stages by identifying hypokinetic dysarthria. MFCC's process speech recognition patterns and produce …


Effects Of Transcranial Direct Current Stimulation On Adults With Post-Acute Covid-19 Syndrome, Isaac Min, Aaron Schurger Nov 2022

Effects Of Transcranial Direct Current Stimulation On Adults With Post-Acute Covid-19 Syndrome, Isaac Min, Aaron Schurger

Student Scholar Symposium Abstracts and Posters

Since its detection in December 2019, coronavirus disease 2019 (COVID-19), the viral disease caused by the SARS-CoV-2 novel coronavirus, has had prominent effects on human health and mortality. Studies in previous infections of SARS-CoV and MERS-CoV have found evidence of persistent symptoms in recovered patients, such as lethargy and shortness of breath. Similar residual symptoms have also been seen in recovered COVID-19 patients beyond four weeks of the initial onset of symptoms — collectively termed post-acute COVID-19 syndrome (PACS). These symptoms include deficits in working memory. Preliminary studies done in the United States and Europe have shown a significant portion …


Understanding Parkinson’S Disease Through Gait Initiation And Center Of Pressure, Mira Ananthanarayanan, Kiara Salceda, Michael Shiraishi, Rahul Soangra Nov 2022

Understanding Parkinson’S Disease Through Gait Initiation And Center Of Pressure, Mira Ananthanarayanan, Kiara Salceda, Michael Shiraishi, Rahul Soangra

Student Scholar Symposium Abstracts and Posters

Parkinson's disease is a neurological disorder that causes tremors and freezing of gait in diagnosed patients. Freezing of gait can be difficult to identify and intervene without laboratory based instruments data collection. Force plates have been proven to show viable results in identifying gait events such as heel contact and toe off. The complete gait cycle consists of a right-heel strike, right heel-to-toe shift, simultaneous right-toe off/left heel strike, left heel-to-toe shift, and a simultaneous left-toe off/right heel strike. This study will investigate center of pressure trajectories when initiating gait between healthy and Parkinson's participants. It is predicted that the …


Efficacy And Safety Of A Brain-Penetrant Biologic Tnf-Α Inhibitor In Aged App/Ps1 Mice, Weijun Ou, Yuu Ohno, Joshua Yang, Devaraj V. Chandrashekar, Tamara Abdullah, Jiahong Sun, Riley Murphy, Chuli Roules, Nataraj Jagadeesan, David H. Cribbs, Rachita K. Sumbria Oct 2022

Efficacy And Safety Of A Brain-Penetrant Biologic Tnf-Α Inhibitor In Aged App/Ps1 Mice, Weijun Ou, Yuu Ohno, Joshua Yang, Devaraj V. Chandrashekar, Tamara Abdullah, Jiahong Sun, Riley Murphy, Chuli Roules, Nataraj Jagadeesan, David H. Cribbs, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Tumor necrosis factor alpha (TNF-α) plays a vital role in Alzheimer’s disease (AD) pathology, and TNF-α inhibitors (TNFIs) modulate AD pathology. We fused the TNF-α receptor (TNFR), a biologic TNFI that sequesters TNF-α, to a transferrin receptor antibody (TfRMAb) to deliver the TNFI into the brain across the blood–brain barrier (BBB). TfRMAb-TNFR was protective in 6-month-old transgenic APP/PS1 mice in our previous work. However, the effects and safety following delayed chronic TfRMAb-TNFR treatment are unknown. Herein, we initiated the treatment when the male APP/PS1 mice were 10.7 months old (delayed treatment). Mice were injected intraperitoneally with saline, TfRMAb-TNFR, etanercept (non-BBB-penetrating …


Modulation Of Hepatic Amyloid Precursor Protein And Lipoprotein Receptor-Related Protein 1 By Chronic Alcohol Intake: Potential Link Between Liver Steatosis And Amyloid-Β, Jerome Garcia, Rudy Chang, Ross A. Steinberg, Aldo Arce, Joshua Yang, Peter Van Der Eb, Tamara Abdullah, Devaraj V. Chandrashekar, Syndey M. Eck, Pablo Meza, Zhang-Xu Liu, Enrique Cadenas, David H. Cribbs, Neil Kaplowitz, Rachita K. Sumbria, Derick Han Sep 2022

Modulation Of Hepatic Amyloid Precursor Protein And Lipoprotein Receptor-Related Protein 1 By Chronic Alcohol Intake: Potential Link Between Liver Steatosis And Amyloid-Β, Jerome Garcia, Rudy Chang, Ross A. Steinberg, Aldo Arce, Joshua Yang, Peter Van Der Eb, Tamara Abdullah, Devaraj V. Chandrashekar, Syndey M. Eck, Pablo Meza, Zhang-Xu Liu, Enrique Cadenas, David H. Cribbs, Neil Kaplowitz, Rachita K. Sumbria, Derick Han

Pharmacy Faculty Articles and Research

Heavy alcohol consumption is a known risk factor for various forms of dementia and the development of Alzheimer’s disease (AD). In this work, we investigated how intragastric alcohol feeding may alter the liver-to-brain axis to induce and/or promote AD pathology. Four weeks of intragastric alcohol feeding to mice, which causes significant fatty liver (steatosis) and liver injury, caused no changes in AD pathology markers in the brain [amyloid precursor protein (APP), presenilin], except for a decrease in microglial cell number in the cortex of the brain. Interestingly, the decline in microglial numbers correlated with serum alanine transaminase (ALT) levels, suggesting …


Full- Versus Sub-Regional Quantification Of Amyloid-Beta Load On Mouse Brain Sections, Yuu Ohno, Riley Murphy, Matthew Choi, Weijun Ou, Rachita K. Sumbria May 2022

Full- Versus Sub-Regional Quantification Of Amyloid-Beta Load On Mouse Brain Sections, Yuu Ohno, Riley Murphy, Matthew Choi, Weijun Ou, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Extracellular accumulation of amyloid-beta (Aβ) plaques is one of the major pathological hallmarks of Alzheimer's disease (AD), and is the target of the only FDA-approved disease-modifying treatment for AD. Accordingly, the use of transgenic mouse models that overexpress the amyloid precursor protein and thereby accumulate cerebral Aβ plaques are widely used to model human AD in mice. Therefore, immunoassays, including enzyme-linked immunosorbent assay (ELISA) and immunostaining, commonly measure the Aβ load in brain tissues derived from AD transgenic mice. Though the methods for Aβ detection and quantification have been well established and documented, the impact of the size of the …


Author Correction: Short Amylin Receptor Antagonist Peptides Improve Memory Deficits In Alzheimer’S Disease Mouse Model, Rania Soudy, Ryoichi Kimura, Aarti Patel, Wen Fu, Kamaljit Kaur, David Westaway, Jing Yang, Jack Jhamandas Apr 2022

Author Correction: Short Amylin Receptor Antagonist Peptides Improve Memory Deficits In Alzheimer’S Disease Mouse Model, Rania Soudy, Ryoichi Kimura, Aarti Patel, Wen Fu, Kamaljit Kaur, David Westaway, Jing Yang, Jack Jhamandas

Pharmacy Faculty Articles and Research

Correction to: Scientific Reports https://doi.org/10.1038/s41598-019-47255-9, published online 29 July 2019

The original Article contained an error in Figure 1A where the control trace for both the HEK-AMY3 and HEKWT cells was duplicated...

The original Article has been corrected.


A Pdk-1 Allosteric Agonist Neutralizes Insulin Signaling Derangements And Beta-Amyloid Toxicity In Neuronal Cells And In Vitro, Henry Querfurth, John Marshall, Keykavous Parang, Mengia S. Rioult-Pedotti, Rakesh Tiwari, Bumsup Kwon, Steve Reisinger, Han-Kyu Lee Jan 2022

A Pdk-1 Allosteric Agonist Neutralizes Insulin Signaling Derangements And Beta-Amyloid Toxicity In Neuronal Cells And In Vitro, Henry Querfurth, John Marshall, Keykavous Parang, Mengia S. Rioult-Pedotti, Rakesh Tiwari, Bumsup Kwon, Steve Reisinger, Han-Kyu Lee

Pharmacy Faculty Articles and Research

The Alzheimer’s brain is affected by multiple pathophysiological processes, which include a unique, organ-specific form of insulin resistance that begins early in its course. An additional complexity arises from the four-fold risk of Alzheimer’s Disease (AD) in type 2 diabetics, however there is no definitive proof of causation. Several strategies to improve brain insulin signaling have been proposed and some have been clinically tested. We report findings on a small allosteric molecule that reverses several indices of insulin insensitivity in both cell culture and in vitro models of AD that emphasize the intracellular accumulation of β-amyloid (Aβi). PS48, a chlorophenyl …


The Company Prosodic Deficits Keep Following Right Hemisphere Stroke: A Systematic Review, Shannon M. Sheppard, Melissa D. Stockbridge, Lynsey M. Keator, Laura L. Murray, Margaret Lehman Blake Jan 2022

The Company Prosodic Deficits Keep Following Right Hemisphere Stroke: A Systematic Review, Shannon M. Sheppard, Melissa D. Stockbridge, Lynsey M. Keator, Laura L. Murray, Margaret Lehman Blake

Communication Sciences and Disorders Faculty Articles and Research

Objectives:

The aim of this systematic review was to identify the presence and nature of relationships between specific forms of aprosodia (i.e., expressive and receptive emotional and linguistic prosodic deficits) and other cognitive-communication deficits and disorders in individuals with right hemisphere damage (RHD) due to stroke.

Methods:

One hundred and ninety articles from 1970 to February 2020 investigating receptive and expressive prosody in patients with relatively focal right hemisphere brain damage were identified via database searches.

Results:

Fourteen articles were identified that met inclusion criteria, passed quality reviews, and included sufficient information about prosody and potential co-occurring …


Biologic Tnf-Α Inhibitors Reduce Microgliosis, Neuronal Loss, And Tau Phosphorylation In A Transgenic Mouse Model Of Tauopathy, Weijun Ou, Joshua Yang, Juste Simanauskaite, Matthew Choi, Demi M. Castellanos, Rudy Chang, Jiahong Sun, Nataraj Jagadeesan, Karen D. Parfitt, David H. Cribbs, Rachita K. Sumbria Dec 2021

Biologic Tnf-Α Inhibitors Reduce Microgliosis, Neuronal Loss, And Tau Phosphorylation In A Transgenic Mouse Model Of Tauopathy, Weijun Ou, Joshua Yang, Juste Simanauskaite, Matthew Choi, Demi M. Castellanos, Rudy Chang, Jiahong Sun, Nataraj Jagadeesan, Karen D. Parfitt, David H. Cribbs, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Background

Tumor necrosis factor-α (TNF-α) plays a central role in Alzheimer’s disease (AD) pathology, making biologic TNF-α inhibitors (TNFIs), including etanercept, viable therapeutics for AD. The protective effects of biologic TNFIs on AD hallmark pathology (Aβ deposition and tau pathology) have been demonstrated. However, the effects of biologic TNFIs on Aβ-independent tau pathology have not been reported. Existing biologic TNFIs do not cross the blood–brain barrier (BBB), therefore we engineered a BBB-penetrating biologic TNFI by fusing the extracellular domain of the type-II human TNF-α receptor (TNFR) to a transferrin receptor antibody (TfRMAb) that ferries the TNFR into the brain via …


Novel Biomarkers Of Ciliary Extracellular Vesicles Interact With Ciliopathy And Alzheimer’S Associated Proteins, Ashraf M. Mohieldin, Amal Alachkar, John R. Yates Iii, Surya M. Nauli Dec 2021

Novel Biomarkers Of Ciliary Extracellular Vesicles Interact With Ciliopathy And Alzheimer’S Associated Proteins, Ashraf M. Mohieldin, Amal Alachkar, John R. Yates Iii, Surya M. Nauli

Pharmacy Faculty Articles and Research

Ciliary extracellular vesicles (ciEVs), released from primary cilia, contain functional proteins that play an important role in cilia structure and functions. We have recently shown that ciEVs and cytosolic extracellular vesicles (cyEVs) have unique and distinct biomarkers. While ciEV biomarkers have shown some interactions with known ciliary proteins, little is known about the interaction of ciEV proteins with proteins involved in ciliopathy and neurodegenerative disorders. Here, we reveal for the first time the protein-protein interaction (PPI) between the top five ciEVs biomarkers with ciliopathy and Alzheimer disease (AD) proteins. These results support the growing evidence of the critical physiological roles …


Functional Seizures: The Patient’S Perspective Of A Diagnostic And Treatment Odyssey, Heather J. Andrini, Sydni L. Au Hoy, Ashley M. Okhovat, Juliana Lockman, Gregory R. Goldsmith Nov 2021

Functional Seizures: The Patient’S Perspective Of A Diagnostic And Treatment Odyssey, Heather J. Andrini, Sydni L. Au Hoy, Ashley M. Okhovat, Juliana Lockman, Gregory R. Goldsmith

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Functional seizures can be challenging to properly diagnose, often leading to delays in treatment. The etiology of functional seizures is multifactorial, with psychological factors identified in many, but not all cases. Misdiagnosis may occur due to clinical features mimicking other medical conditions. Once a correct diagnosis is reached, delivery of definitive, evidence-based treatment may be challenging due to limited availability of specialized resources. Research shows psychological education and cognitive behavioral therapy (CBT) have the greatest efficacy. However, individual differences, including acceptance of the diagnosis, therapeutic alliance, duration of symptoms, comorbidities, and access to care may influence outcomes. There is a …


The Concentration Of Brain Homogenates With The Amicon Ultra Centrifugal Filters, Joshua Yang, Rachita K. Sumbria Nov 2021

The Concentration Of Brain Homogenates With The Amicon Ultra Centrifugal Filters, Joshua Yang, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Accurately measuring the brain concentration of a neurotherapeutic is critical in determining its pharmacokinetic profile in vivo. Biologics are potential therapeutics for neurologic diseases and biologics fused to an antibody targeting a transcytosis receptor at the Blood-Brain Barrier, designated as antibody-biologic fusion proteins, are Blood-Brain Barrier penetrating neurotherapeutics. The use of sandwich immunosorbent assays to measure concentrations of antibody-biologic fusion proteins in brain homogenates has become increasingly popular. The raw brain homogenate contains many proteins and other macromolecules that can cause a matrix effect, potentially interfering with the limit of detection of such assays and reduce the overall sample …


Kinematic Assessment Of Turning And Walking Tasks Among Stroke Survivors By Employing Wearable Sensors And Pressure Platform, Masoud Abdollahi, Pranav Madhav Kuber, Christopher Hoang, Michael Shiraishi, Rahul Soangra, Ehsan Rashedi Nov 2021

Kinematic Assessment Of Turning And Walking Tasks Among Stroke Survivors By Employing Wearable Sensors And Pressure Platform, Masoud Abdollahi, Pranav Madhav Kuber, Christopher Hoang, Michael Shiraishi, Rahul Soangra, Ehsan Rashedi

Physical Therapy Faculty Articles and Research

Stroke survivors often experience reduced movement capabilities due to alterations in their neuromusculoskeletal systems. Modern sensor technologies and motion analyses can facilitate the determination of these changes. Our work aims to assess the potential of using wearable motion sensors to analyze the movement of stroke survivors and identifying the affected functions. We recruited 10 participants (5 stroke survivors, 5 healthy individuals) and conducted a controlled laboratory evaluation for two of the most common daily activities: turning and walking. Among the extracted kinematic parameters, range of trunk and sacrum lateral bending in turning were significantly larger in stroke survivors (p-value<0.02). However, no statistical difference in mean angular velocity and range of motion for trunk/sacrum/shank flexion-extension were obtained in the turning task. Our results also indicated that during walking, while there was no difference in swing time, double support portion of gait among the stroke group was significantly larger (p-value = 0.001). Outcomes of this investigation may help in designing new rehabilitation programs for stroke and other neurological disorders and/or in improving the efficacy of such programs.Clinical Relevance— This study may provide a better insight on the detailed functional differences between stroke survivors and healthy individuals which in turn could be used to develop a more efficient rehabilitation program for stroke community.


Self-Paced Treadmills Do Not Allow For Valid Observation Of Linear And Nonlinear Gait Variability Outcomes In Patients With Parkinson’S Disease, Maryam Rohafza, Rahul Soangra, Jo Armour Smith, Niklas König Ignasiak Oct 2021

Self-Paced Treadmills Do Not Allow For Valid Observation Of Linear And Nonlinear Gait Variability Outcomes In Patients With Parkinson’S Disease, Maryam Rohafza, Rahul Soangra, Jo Armour Smith, Niklas König Ignasiak

Physical Therapy Faculty Articles and Research

Background

Due to the imposed constant belt speed, motorized treadmills are known to affect linear and nonlinear gait variability outcomes. This is particularly true of patients with Parkinson’s Disease where the treadmill can act as an external pacemaker. Self-paced treadmills update the belt speed in response to the subject's walking speed and might, therefore, be a useful tool for measurement of gait variability in this patient population. This study aimed to compare gait variability during walking at self-paced and constant treadmill speeds with overground walking in individuals with PD and individuals with unimpaired gait.

Methods

Thirteen patients with Parkinson’s Disease …


Dysfunctional Tissue Correlates Of Unrelated Naming Errors In Acute Left Hemisphere Stroke, Erin L. Meier, Shannon M. Sheppard, Emily B. Goldberg, Catherine R. Kelly, Alexandra Walker, Delaney M. Ubellacker, Emilia Vitti, Kristina Ruch, Argye E. Hillis Sep 2021

Dysfunctional Tissue Correlates Of Unrelated Naming Errors In Acute Left Hemisphere Stroke, Erin L. Meier, Shannon M. Sheppard, Emily B. Goldberg, Catherine R. Kelly, Alexandra Walker, Delaney M. Ubellacker, Emilia Vitti, Kristina Ruch, Argye E. Hillis

Communication Sciences and Disorders Faculty Articles and Research

Most naming error lesion-symptom mapping (LSM) studies have focused on semantic and/or phonological errors. Anomic individuals also produce unrelated word errors, which may be linked to semantic or modality-independent lexical deficits. To investigate the neural underpinnings of rarely-studied unrelated errors, we conducted LSM analyses in 100 individuals hospitalised with a left hemisphere stroke who completed imaging protocols and language assessments. We used least absolute shrinkage and selection operator regression to capture relationships between naming errors and dysfunctional brain tissue metrics (regional damage or hypoperfusion in vascular territories) in two groups: participants with and without impaired single-word auditory comprehension. Hypoperfusion—particularly within …


Does Subthalamic Deep Brain Stimulation Impact Asymmetry And Dyscoordination Of Gait In Parkinson’S Disease?, Deepak K. Ravi, Christian R. Baumann, Elena Bernasconi, Michelle Gwerder, Niklas K. Ignasiak, Mechtild Uhl, Lennart Stieglitz, William R. Taylor, Navrag B. Singh Sep 2021

Does Subthalamic Deep Brain Stimulation Impact Asymmetry And Dyscoordination Of Gait In Parkinson’S Disease?, Deepak K. Ravi, Christian R. Baumann, Elena Bernasconi, Michelle Gwerder, Niklas K. Ignasiak, Mechtild Uhl, Lennart Stieglitz, William R. Taylor, Navrag B. Singh

Physical Therapy Faculty Articles and Research

Background. Subthalamic deep brain stimulation (STN-DBS) is an effective treatment for selected Parkinson’s disease (PD) patients. Gait characteristics are often altered after surgery, but quantitative therapeutic effects are poorly described. Objective. The goal of this study was to systematically investigate modifications in asymmetry and dyscoordination of gait 6 months postoperatively in patients with PD and compare the outcomes with preoperative baseline and to asymptomatic controls without PD. Methods. A convenience sample of thirty-two patients with PD (19 with postural instability and gait disorder (PIGD) type and 13 with tremor dominant disease) and 51 asymptomatic controls participated. Parkinson patients …