Nervous System Diseases Commons^™

The Mitochondria Is The Source Of Hepatic Amyloid Precursor Protein And Peripheral Amyloid Beta: Implications Of Alcohol-Induced Liver Steatosis In Alzheimer's Disease, Josephine Chu, Ross A. Steinberg, Brian Carson, Devaraj Venkatapura Chandrashekar, Rachita K. Sumbria, Derick Han

Pharmacy Faculty Articles and Research

Background

Alcohol-induced liver injury occurs in the pericentral region of the liver and can induce mitochondrial remodeling and exacerbate Alzheimer's Disease (AD) progression. Subpopulations of mitochondria: general mitochondria (GM), peridroplet mitochondria (PDM) and endoplasmic reticulum(ER)-bound mitochondria (ERM) maintain cellular homeostasis via energy synthesis, lipid homeostasis, and regulation of intracellular calcium. Hepatic amyloid precursor protein (APP) is a source of peripheral amyloid beta (aB) and affects AD pathology in the brain. Understanding the localization and expression of hepatic APP in mitochondrial subpopulations are critical to understanding aB metabolism and may play a role in identifying a potential mechanism for metabolic dysfunction. …

Bcl-2 Regulation As Seen In Alzheimer's Disease, Whitley Whitehead, Joseph Marek, Jack Lowry, Parker Shirley

Student Scholar Symposium

Alzheimer’s Disease (AD) is a degenerative and destructive disorder causing progressive impairment and loss of the nerve cells, eventually leading to further impairments of cognitive functions. Calcium ions (Ca2+) are vital for cell signaling and muscle contraction. The Bcl-2 protein family helps regulate cell death by controlling the release of Ca2+ from the ER. Bcl-2 can also block pro-apoptotic proteins from puncturing the mitochondria and causing intrinsic apoptosis. In AD, the presence of amyloid-beta plaques and neurofibrillary tangles downregulates Bcl-2 production. The loss of Bcl-2 leads to mitochondrial damage, heightened calcium levels, and oxidative stress. Although there is no cure …

Transient Neuromonitoring Changes And Delayed Vertebrobasilar Infarction Following Anterior Cervical Discectomy And Fusion: Illustrative Case, Jacob M. Chaisson, Jack A. Leoni, Ellery A. Hayden, Gabriel C. Tender, Amit K. Bhandutia

School of Medicine Faculty Publications

BACKGROUND: Anterior cervical discectomy and fusion (ACDF) is a common spinal procedure with a well-established safety profile. While direct vertebral artery injury is rare and typically recognized intraoperatively, delayed posterior circulation stroke is an even less common but major complication. In patients with risk factors for vascular disease, vascular stress from surgical manipulation may predispose them to thromboembolic events that are not immediately apparent. Transient intraoperative neuromonitoring (IONM) changes may represent early, underrecognized indicators of such vascular compromise. OBSERVATIONS: The authors present the case of a 61-year-old male who underwent elective three-level ACDF for degenerative cervical myelopathy. During cage placement, …

Comprehensive Analysis Platform To Understand, Remedy, And Eliminate Amyotrophic Lateral Sclerosis (Capture Als): Study Protocol For A Canadian Multicenter, Multimodal, Longitudinal Observational Study, Natalie Saunders, Claire Magnussen, Hyungmo Kang, Mathieu Blais, Harpreet Bhinder, Gerald Pfeffer, Shelagh K. Genuis, Liziane Bouvier, Tanushka Anand, Tania M. Bubela

Office of the Provost

Background: The marked heterogeneity of Amyotrophic Lateral Sclerosis (ALS) combined with a lack of biomarkers are key contributing factors to the lack of disease-modifying treatments. The Comprehensive Analysis Platform to Understand Remedy and Eliminate ALS (CAPTURE ALS) is a Canadian platform designed to create the most comprehensive picture of people living with ALS with the objective of facilitating ALS research initiatives worldwide.
Objectives: The main aims of CAPTURE ALS include: (1) to characterize ALS and healthy controls with biosamples and data in order to provide the most comprehensive picture of individuals living with ALS to date; (2) to create a …

Longitudinal Pharmacokinetic And Safety Studies Of An Antibody-Erythropoietin Fusion Protein For Alzheimer's Disease, Rudy Chang, Devaraj Venkatapura Chandrashekar, G. Chuli Roules, Nataraj Jagadeesan, Emi Iwasaki, Adenike Oyegbesan, Hayk Davtyan, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Erythropoietin (EPO) shows promise for Alzheimer's disease (AD) but has poor brain penetration, necessitating high doses that cause hematopoietic side effects. To improve brain delivery, EPO was fused to a transferrin receptor monoclonal antibody (TfRMAb), and this study evaluated the pharmacokinetics (PK), safety, and efficacy of repeated TfRMAb-EPO dosing in mice to further its preclinical development. C57BL/6J male mice (10 weeks old, n = 4–5/dose) received subcutaneous (SQ) low (1 mg/kg), mid (3 and 6 mg/kg), or high (20 mg/kg) TfRMAb-EPO doses for 4 weeks. The 1 mg/kg dose showed no adverse effects and resulted in sustained brain and plasma …

Overview Of Huntington's Disease And Emerging Treatment Strategies: A Narrative Review, Alexis J. Vega, Gabriel V. Hernandez, Pearse A. O'Malley, Connor J. Robin, Amanda N. Parra, Giustino Varrassi, Sahar Shekoohi, Alan D. Kaye

School of Medicine Faculty Publications

Huntington's disease (HD) is an autosomal dominant, progressive neurodegenerative disorder caused by a cytosine-adenine-guanine trinucleotide repeat expansion in the huntingtin (HTT) gene. The symptoms of HD include severe motor dysfunction, cognitive issues, and emotional dysregulation. These combined issues are not only debilitating but also lead to depression/anxiety, increased suicide rates, and caregiver burnout. Our narrative review summarizes several recent studies examining the efficacy and differences among emerging treatment strategies for HD. A systematic search of peer-reviewed literature was conducted, focusing on recent studies that describe molecular genetic manipulation of the HTT gene/huntingtin protein. The results of our narrative review reveal …

The Mechanism Of Action Of Remote Electrical Neuromodulation (Ren) In Treating Migraine And Potentially Other Idiopathic Pain Conditions, Marius Birlea, Christopher L. Robinson, Eden Mama, Alit Stark-Inbar, Alon Ironi, Daniel Atashsokhan, Thomas Berk

College of Nursing Faculty Papers & Presentations

Purpose of Review

This review provides evidence for the mechanism of action (MOA) of Remote Electrical Neuromodulation (REN), a non-pharmacological therapeutic technology for treating migraine and other symptoms manifested by certain idiopathic pain diseases. It discusses the main physiological and anatomical aspects associated with conditioned pain modulation (CPM), and how REN is applied for the treatment of migraine pain and other symptoms.

Recent Findings

The REN wearable device (Nerivio®) is FDA cleared for acute and preventive treatment of migraine in patients aged 8 years and above, and CE marked in patients aged 12 and above. In brief, the REN MOA …

Dietary Fiber Modulates Gut Microbiota And Lipid Metabolism Ameliorating Alzheimer's Pathology In 5xfad Mice, Yuhai Zhao, Christopher M. Taylor, Walter J. Lukiw, Nicolas G. Bazan

School of Graduate Studies Faculty Publications

The gut-brain axis plays a critical role in maintaining neuronal integrity and influencing the progression of Alzheimer's disease (AD). Here, we investigated how commonly consumed dietary fibers modulate gut microbiota, lipid metabolism, and AD pathology in 5xFAD mice. Male mice were fed either fiber-free (FF) or fiber-plus (FP; 1% cellulose, 2% pectin, 2% inulin) diets for five months, followed by integrated analyses of gut microbiota (16 S rRNA sequencing), fecal lipid metabolites (LC-MS/MS), and neuropathological and behavioral outcomes. FP diets markedly altered microbial composition, characterized by increases in Muribaculaceae, Ileibacterium, and Lachnospiraceae NK4A136 group and reductions in Faecalibaculum and Coriobacteriaceae …

Diurnal Behavioral Outcomes And Bbb Integrity In Adult Male Shr And Wky Rats, Pallavi Shrivastava, Oluchukwu D. Biose, Riya Dahal, Abdallah Jwayyed, Rukayat A. Raji, Huijing Xia, Eric Lazartigues, Ifechukwude J. Biose

School of Graduate Studies Faculty Publications

Day and night neurobehavioral tests were performed for Spontaneously Hypertensive rats (SHR) and Wistar Kyoto rats (WKY) to establish an optimal testing window. Also, blood–brain barrier (BBB) integrity in brain areas related to cognition was measured to determine strain-specific differences. Six months old male SHR and WKY were randomly divided into day (i.e., 9–11 a.m.) and nighttime (i.e., 7–9 p.m.) testing regimen. Neurobehavioral tests included: Y-maze spontaneous alternation, open field, novel object recognition (NOR), and tail suspension test (TST). BBB integrity was measured in the cortex, hippocampus and striatum. WKY showed higher recognition memory at night compared to SHR and …

Effect Of Neuroinflammation On Exploratory Behavior In Mice, Gage Pompa, Ariana Mitic, Yader Gomez, Lilian Hagos, Orlando Montiel

Undergraduate Research Symposium Posters

Introduction: Mice have been observed in both laboratory and field settings to exhibit a tendency to remain near corners and walls. This trait is known as positive thigmotaxis. Thigmotaxis has been recognized as a fundamental aspect of rodent behavior and used extensively as an anxiety index in mice. Although this characteristic has been recognized as a fundamental aspect of rodent behavior, thigmotaxis has been extensively studied in rectangular and circular environments. However, there is a notable lack of understanding of how alternative geometric configurations can influence this behavior.

Methods and Approach: Using a grid overlaid on the environment the mice …

Extensive Spinal Epidural Abscess Evacuated With Unilateral Interlaminar Approach (With Operative Video): Illustrative Case, George A. Crabill, Jack A. Leoni, Kaleb Derouen, Jamieson Glasser, Wesley Shoap, Gabriel Tender

School of Medicine Faculty Publications

BACKGROUND: The authors present the case of a patient with an extensive lumbosacral spinal epidural abscess (SEA) that was successfully evacuated in its entirety with a unilateral interlaminar approach. This is an alternative to wide bony decompression at multiple segments. The surgical approach described decompresses the neural elements while maintaining spinal integrity. OBSERVATIONS: Partial removal of the ligamentum flavum can provide an interlaminar corridor that is sufficient to evacuate extensive SEAs in select patients. LESSONS: This case illustrates a surgical approach that successfully evacuates extensive lumbosacral SEA while respecting spinal integrity. https://thejns.org/doi/abs/10.3171/CASE25646.

Intercellular Signaling And Synaptic Deconstruction Uncovered By Single-Cell And Spatial Transcriptomics In An Ad Tauopathy Model, Jeff X. Ji, Brian L. Giles, Surjyadipta Bhattacharjee, Marie-Audrey I. Kautzmann, Alasdair P. Masson, Sonia Do Carmo, A Claudio Cuello, Nicolas G. Bazan

School of Medicine Faculty Publications

Alzheimer's disease (AD) is the leading cause of dementia in elderly individuals worldwide; however, all mechanisms leading to disease onset and progression are not well understood. Here, we report brain single-cell multiome and spatial transcriptomics in a transgenic rat model of human-like tauopathy. We have identified new markers of tau-driven AD pathology and provided single-cell evidence for genes implicated in AD. Our findings reveal how tau hyperphosphorylation and aging alter ligand-receptor communication, transcription factor regulatory networks, and specific cellular networks. Notably, we found intriguing changes in cell communication involving glutamatergic transmission and Netrin signaling as a taupathy consequence. Overall, this …

Promising Effects Of Car T-Cell Therapy In Refractory Stiff Person Syndrome And A Hopeful Future For All Neuroautoimmunities, Marinos Dalakas

Department of Neurology Faculty Papers

Chimeric antigen receptor (CAR) T cells are genetically modified T cells expressing CARs, initially developed to recognize tumor antigens and kill cancer cells that evade T-cell recognition. Because of their impressive success in hemato-oncologic malignancies, CAR T cells are being repurposed with redesigned constructs for safety and sustained efficacy to target refractory systemic autoimmune or neurologic diseases. The CD19 CAR T cells-targeting those CD19-positive, antibody-secreting, long-lived plasma cells, and plasmablasts-are now extensively explored in refractory neuroautoimmunities with promising benefits based on case series in patients with myasthenia gravis (MG), stiff person syndrome (SPS), neuromyelitis, myositis, and multiple sclerosis; some patients …

Repetitive Head Impacts: Definitional Challenges, Clinical Implications, And Research Directions, Amanda Rabinowitz, Allie Tracey, Yevgeniya Sergeyenko

Department of Rehabilitation Medicine Faculty Papers

Purpose of Review: Repetitive head impacts (RHI)—repeated head trauma that may or may not result in clinically identified injury—are a growing public health concern due to links with neurodegenerative disease and long-term dysfunction. This review aimed to synthesize current knowledge of RHI and evaluate methodological challenges that limit conclusions about its clinical consequences. Recent Findings: Emerging studies highlight associations between RHI and cognitive, emotional, and functional outcomes across vulnerable populations including athletes, military personnel, and survivors of intimate partner violence. However, definitional ambiguity, difficulties in measuring exposure, and population-specific confounds continue to hinder progress. Clinical approaches emphasize individualized assessment and …

Editorial: Bridging Inflammation, Oxidative Stress, And Metabolic Dysfunction In Brain Disorders, Ansab Akhtar

School of Medicine Faculty Publications

We present this Special Issue of Brain Sciences, titled "Role of Inflammation, Oxidative Stress, and Metabolic Dysfunction in Neurodevelopmental and Neurodegenerative Diseases: Pharmacological Targets and Therapeutic Interventions", which brings together research and review articles that explore the molecular crosstalk between neuroinflammatory, oxidative stress, and metabolic pathways underlying both neurodegenerative and neurodevelopmental disorders [...].

Botulinum Toxin In Stiff Person Syndrome: How Useful Is It In Helping Muscle Stiffness And Spasms?, Marinos Dalakas

Department of Neurology Faculty Papers

No abstract provided.

Rebound Bursting Selectively Enables Fast Dynamics In Dopamine Midbrain Neurons Projecting To The Dorsolateral Striatum, Strahinja Stojanovic, Christopher J. Knowlton, Richard Egger-Mackrodt, Johanna Mankel, Josef Shin, Stephan Lammel, Carmen C. Canavier, Jochen Roeper

School of Graduate Studies Faculty Publications

Dopamine (DA) midbrain neurons are involved in a wide array of key brain functions including movement control and reward-based learning. They are also critical for major brain disorders such as Parkinson's disease or schizophrenia. DA neurons projecting to distinct striatal territories are diverse with regard to their molecular makeup and cellular physiology, which are likely to contribute to the observed differences in temporal DA dynamics. Among these regions, the dorsolateral striatum (DLS) displays the fastest DA dynamics, which might control the moment-to-moment vigor and variability of voluntary movements. However, the underlying mechanisms for these DLS-specific fast DA fluctuations are unresolved. …

Comprehensive Descriptive Analysis Of Large Alzheimer's Disease Patient Cohorts, Ehsan Yaghmaei, Attallah Dillard, Mohammadreza Rezaei, Ahmad Razaei, Albert Pierce, Hongxia Lu, Eric Adams, Nikolay Todorov, Louis Ehwerhemuepha, Jianwei Zheng, Seyed Ahmad Sajjadi, Mohsen Bazargan, Cyril Rakovski

Mathematics, Physics, and Computer Science Faculty Articles and Research

Background

Objective

Methods

Cerebellar Dysfunction In Glaucoma Patients, Anisha Kasi, Ji Won Bang, Vivek Trivedi, Jeannie Au, Ian Conner, Gadi Wollstein, Joel Schuman, Rakie Cham, Kevin Chan

Wills Eye Hospital Papers

Glaucoma patients often have higher injurious fall rates compared to healthy older adults. However, little is known about the underlying neural mechanisms. Recent evidence shows cerebral changes beyond the visual pathway of glaucoma patients, yet it remains unclear whether the cerebellum, which plays an important role in balance and motor control, is involved in glaucoma. In this study, we sought to investigate cerebellar functional connectivity changes in glaucoma by comparing 32 glaucoma subjects and 10 age-matched healthy control subjects who underwent resting-state functional magnetic resonance imaging at 3 Tesla with eyes closed. After conducting both regions-of-interest and seed-to-voxel analyses, we …

Twenty Minutes Of Corsi Block Tapping Task Training Does Not Improve Mental Rotation In Adults With Stroke, Sarah A. Kettlety, Giuliet L. Kibler, Andrew Hooyman, Christina K. Holl, Sydney Y. Schaefer, Kristan A. Leech

Physical Therapy Faculty Articles and Research

Background: Visuospatial function is commonly impaired post-stroke and is associated with motor learning and recovery. A single, twenty-minute Corsi Block Tapping Task (CBTT) training session improved visuospatial function in young neurotypical adults; however, it is unclear whether this training would improve visuospatial function in adults with stroke.

Objective: To understand if a single, twenty-minute CBTT training session improved visuospatial function in adults with stroke compared to a no-training control group of adults with stroke.

Methods: Participants post-stroke were assigned to one of two groups. The training group completed twenty minutes of computerized CBTT training. The control group completed a survey …