Nervous System Diseases Commons^™

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 …

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 …

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 …

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

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.

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 …

Scoping Review: The Empowerment Of Alzheimer’S Disease Caregivers With Mhealth Applications, Eunhee Kim, Andrius Baskys, Anandi V. Law, Moom R. Roosan, Yan Li, Don Roosan

Pharmacy Faculty Articles and Research

Alzheimer’s Disease (AD) is one of the most prevalent neurodegenerative chronic diseases. As it progresses, patients become increasingly dependent, and their caregivers are burdened with the increasing demand for managing their care. Mobile health (mHealth) technology, such as smartphone applications, can support the need of these caregivers. This paper examines the published academic literature of mHealth applications that support the caregivers of AD patients. Following the PRISMA for scoping reviews, we searched published literature in five electronic databases between January 2014 and January 2021. Twelve articles were included in the final review. Six themes emerged based on the functionalities provided …

The Mechanism Of Β-N-Methylamino-L-Alanine Inhibition Of Trna Aminoacylation And Its Impact On Misincorporation, Nien-Ching Han, Tammy J. Bullwinkle, Kaeli F. Loeb, Kym F. Faull, Kyle Mohler, Jesse Rinehart, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

β-N-methylamino-l-alanine (BMAA) is a nonproteinogenic amino acid that has been associated with neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD). BMAA has been found in human protein extracts; however, the mechanism by which it enters the proteome is still unclear. It has been suggested that BMAA is misincorporated at serine codons during protein synthesis, but direct evidence of its cotranslational incorporation is currently lacking. Here, using LC-MS–purified BMAA and several biochemical assays, we sought to determine whether any aminoacyl-tRNA synthetase (aaRS) utilizes BMAA as a substrate for aminoacylation. Despite BMAA's previously predicted misincorporation at serine …

Diagnosing And Managing Post-Stroke Aphasia, Shannon M. Sheppard, Rajani Sebastian

Communication Sciences and Disorders Faculty Articles and Research

Introduction: Aphasia is a debilitating language disorder and even mild forms of aphasia can negatively affect functional outcomes, mood, quality of life, social participation, and the ability to return to work. Language deficits after post-stroke aphasia are heterogeneous.

Areas covered: The first part of this manuscript reviews the traditional syndrome-based classification approach as well as recent advances in aphasia classification that incorporate automatic speech recognition for aphasia classification. The second part of this manuscript reviews the behavioral approaches to aphasia treatment and recent advances such as noninvasive brain stimulation techniques and pharmacotherapy options to augment the effectiveness of …

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

Recent evidence supports involvement of amylin and the amylin receptor in the pathogenesis of Alzheimer’s disease (AD). We have previously shown that amylin receptor antagonist, AC253, improves spatial memory in AD mouse models. Herein, we generated and screened a peptide library and identified two short sequence amylin peptides (12–14 aa) that are proteolytically stable, brain penetrant when administered intraperitoneally, neuroprotective against Aβ toxicity and restore diminished levels of hippocampal long term potentiation in AD mice. Systemic administration of the peptides for five weeks in aged 5XFAD mice improved spatial memory, reduced amyloid plaque burden, and neuroinflammation. The common residue SQELHRLQTY …

Systematic Literature Review Of Quetiapine For The Treatment Of Psychosis In Patients With Parkinsonism, Jack J. Chen, Henry Hua, Lilian Massihi, Ivan Portillo, Azita Alipour, William Ondo, Khashayar Dashtipour

Library Articles and Research

Objective:

The purpose of this article was to determine the efficacy and tolerability of quetiapine compared with placebo or other interventions for psychosis in parkinsonism.

Methods:

Participants with a diagnosis of parkinsonism participated in randomized controlled trials (RCTs) investigating the efficacy and tolerability of quetiapine for psychotic symptoms within a defined follow-up period. The authors conducted searches on PubMed, Cochrane Controlled Register of Trials, and EMBASE for articles published from January 1991 to October 2017. Study methodology and patient- and treatment-level data were independently extracted and summarized by using descriptive statistics. Studies underwent quality assessment for risk of bias.

Results: …

Variant Intestinal-Cell Kinase In Juvenile Myoclonic Epilepsy, J. N. Bailey, L. De Nijs, D. Bai, T. Suzuki, H. Miyamoto, M. Tanaka, C. Patterson, Y.-C. Lin, M. T. Medina, M. E. Alonso, J. M. Serratosa, R. M. Durón, Viet-Hong Nguyen, J. E. Wight, I. E. Martínez‑Juárez, A. Ochoa, A. Jara-Prado, L. Guilhoto, Y. Molina, E. M. Yacubian, M. López‑Ruiz, Y. Inoue, S. Kaneko, S. Hirose, M. Osawa, H. Oguni, S. Fujimoto, T. M. Grisar, J. M. Stern, K. Yamakawa, B. Lakaye, A. V. Delgado-Escueta

Pharmacy Faculty Articles and Research

BACKGROUND

In juvenile myoclonic epilepsy, data are limited on the genetic basis of networks promoting convulsions with diffuse polyspikes on electroencephalography (EEG) and the subtle microscopic brain dysplasia called microdysgenesis.

METHODS

Using Sanger sequencing, we sequenced the exomes of six members of a large family affected with juvenile myoclonic epilepsy and confirmed cosegregation in all 37 family members. We screened an additional 310 patients with this disorder for variants on DNA melting-curve analysis and targeted real-time DNA sequencing of the gene encoding intestinal-cell kinase (ICK). We calculated Bayesian logarithm of the odds (LOD) scores for cosegregating variants, odds …

Repeat-Associated Non-Aug (Ran) Translation And Other Molecular Mechanisms In Fragile X Tremor Ataxia Syndrome, M. Rebecca Glineburg, Peter K. Todd, Nicolas Charlet-Berguerand, Chantal Sellier

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset inherited neurodegenerative disorder characterized by progressive intention tremor, gait ataxia and dementia associated with mild brain atrophy. The cause of FXTAS is a premutation expansion, of 55 to 200 CGG repeats localized within the 5′UTR of FMR1. These repeats are transcribed in the sense and antisense directions into mutants RNAs, which have increased expression in FXTAS. Furthermore, CGG sense and CCG antisense expanded repeats are translated into novel proteins despite their localization in putatively non-coding regions of the transcript. Here we focus on two proposed disease mechanisms for FXTAS: 1) RNA …

Ran Translation At C9orf72-Associated Repeat Expansions Is Selectively Enhanced By The Integrated Stress Response, Katelyn M. Green, M. Rebecca Glineburg, Michael G. Kearse, Brittany N. Flores, Alexander E. Linsalata, Stephen J. Fedak, Aaron C. Goldstrohm, Sami J. Barmada, Peter K. Todd

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Repeat-associated non-AUG (RAN) translation allows for unconventional initiation at disease-causing repeat expansions. As RAN translation contributes to pathogenesis in multiple neurodegenerative disorders, determining its mechanistic underpinnings may inform therapeutic development. Here we analyze RAN translation at G₄C₂ repeat expansions that cause C9orf72-associated amyotrophic lateral sclerosis and frontotemporal dementia (C9RAN) and at CGG repeats that cause fragile X-associated tremor/ataxia syndrome. We find that C9RAN translation initiates through a cap- and eIF4A-dependent mechanism that utilizes a CUG start codon. C9RAN and CGG RAN are both selectively enhanced by integrated stress response (ISR) activation. ISR-enhanced RAN translation requires an …

Structural Insights Into The Potency Of Sk Channel Positive Modulators, Young-Woo Nam, Razan Orfali, Tingting Liu, Kunqian Yu, Meng Cui, Heike Wulff, Miao Zhang

Pharmacy Faculty Articles and Research

Small-conductance Ca2+-activated K+ (SK) channels play essential roles in the regulation of cellular excitability and have been implicated in neurological and cardiovascular diseases through both animal model studies and human genetic association studies. Over the past two decades, positive modulators of SK channels such as NS309 and 1-EBIO have been developed. Our previous structural studies have identified the binding pocket of 1-EBIO and NS309 that is located at the interface between the channel and calmodulin. In this study, we took advantage of four compounds with potencies varying over three orders of magnitude, including 1-EBIO, NS309, SKS-11 (6-bromo-5-methyl-1H-indole-2,3-dione-3-oxime) and …

Alzheimer’S Disease: Dawn Of A New Era?, Farideh Amirrad, Emira Bousoik, Kiumars Shamloo, Hassan Al-Shiyab, Viet-Hong Nguyen, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

Alzheimer’s disease (AD) is an irreversible neurodegenerative disease characterized by a progressive decline in cognition and memory, leading to significant impairment in daily activities and ultimately death. It is the most common cause of dementia, the prevalence of which increases with age; however, age is not the only predisposing factor. The pathology of this cognitive impairing disease is still not completely understood, which has limited the development of valid therapeutic options. Recent years have witnessed a wide range of novel approaches to combat this disease, so that they greatly increased our understanding of the disease and of the unique drug …

Cyclic Ac253, A Novel Amylin Receptor Antagonist, Improves Cognitive Deficits In A Mouse Model Of Alzheimer’S Disease, Rania Soudy, Aarti Patel, Wen Fu, Kamaljit Kaur, David Mactavish, David Westaway, Rachel Davey, Jeffrey Zajac, Jack Jhamandas

Pharmacy Faculty Articles and Research

Introduction: Amylin receptor serves as a portal for the expression of deleterious effects of amyloid b-protein (Ab), a key pathologic hallmark of Alzheimer’s disease. Previously, we showed that AC253, an amylin receptor antagonist, is neuroprotective against Ab toxicity in vitro and abrogates Ab-induced impairment of hippocampal long-term potentiation.

Methods: Amyloid precursor protein–overexpressing TgCRND8 mice received intracerebroventricularly AC253 for 5 months. New cyclized peptide cAC253 was synthesized and administered intraperitoneally three times a week for 10 weeks in the same mouse model. Cognitive functions were monitored, and pathologic changes were quantified biochemically and immunohistochemically.

Results: AC253, when administered …

Can Gait Signatures Provide Quantitative Measures For Aiding Clinical Decision-Making? A Systematic Meta-Analysis Of Gait Variability Behavior In Patients With Parkinson’S Disease, Niklas König Ignasiak

Physical Therapy Faculty Articles and Research

A disturbed, inconsistent walking pattern is a common feature of patients with Parkinson's disease (PwPD). Such extreme variability in both temporal and spatial parameters of gait has been associated with unstable walking and an elevated prevalence of falls. However, despite their ability to discretise healthy from pathological function, normative variability values for key gait parameters are still missing. Furthermore, an understanding of each parameter's response to pathology, as well as the inter-parameter relationships, has received little attention. The aim of this systematic literature review and meta-analysis was therefore to define threshold levels for pathological gait variability as well as to …

Revealing The Quality Of Movement: A Meta-Analysis Review To Quantify The Thresholds To Pathological Variability During Standing And Walking, Niklas König Ignasiak

Physical Therapy Faculty Articles and Research

Neuromotor processes are inherently noisy, which results in variability during movement and fluctu-ations in motor control. Although controversial, low levels of variability are traditionally considered healthy, while increased levels are thought to be pathological. This systematic review and meta-analysisof the literature investigates the thresholds between healthy and pathological task variability.

After examining 13,195 publications, 109 studies were included. Results from over 3000 healthy sub-jects and 2775 patients revealed an overall positive effect size of pathology on variability of 0.59 forwalking and 0.80 for sway. For the coefficient of variation of stride time (ST) and sway area (SA), upperthresholds of 2.6% …

Connectivity Measures Are Robust Biomarkers Of Cortical Function And Plasticity After Stroke, Jennifer Wu, Erin Burke Quinlan, Lucy Dodakian, Alison Mckenzie, Nikhita Kathuria, Robert J. Zhou, Renee Augsburger, Jill See, Vu H. Lee, Ramesh Srinivasan, Steven C. Cramer

Physical Therapy Faculty Articles and Research

Valid biomarkers of motor system function after stroke could improve clinical decision-making. Electroencephalography-based measures are safe, inexpensive, and accessible in complex medical settings and so are attractive candidates. This study examined specific electroencephalography cortical connectivity measures as biomarkers by assessing their relationship with motor deficits across 28 days of intensive therapy. Resting-state connectivity measures were acquired four times using dense array (256 leads) electroencephalography in 12 hemiparetic patients (7.3 ± 4.0 months post-stroke, age 26–75 years, six male/six female) across 28 days of intensive therapy targeting arm motor deficits. Structural magnetic resonance imaging measured corticospinal tract injury and infarct volume. …