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Perivascular Waste Metabolites Clearance In Central Nervous System (Cns), Yiming Cheng 2019 New Jersey Institute of Technology

Perivascular Waste Metabolites Clearance In Central Nervous System (Cns), Yiming Cheng

Dissertations

Efficient clearance of interstitial waste metabolites is essential for normal brain homeostasis. Such effective clearance is hampered by the lack of a lymphatic system in the brain, and the cerebrospinal fluid (CSF) is unable to clear large size waste metabolites in the brain. Here, a novel idea that brain arterial endothelium and smooth muscle cells reactivity regulates the clearance of these water-insoluble large size waste metabolites through the perivascular dynamic exchange, and that low dose ethanol promotes this perivascular clearance is proposed.

In Aim 1, the biodistribution of a large size waste metabolite (Amyloid-β protein mimic) in rat perivascular space ...


Cognitively Normal Women With Alzheimer’S Disease Proteinopathy Show Relative Preservation Of Memory But Not Of Hippocampal Volume, Jessica Z.K. Caldwell, Jeffrey L. Cummings, Sarah J. Banks, Sebastian Palmqvist, Oskar Hansson 2019 Cleveland Clinic Lou Ruvo Center for Brain Health

Cognitively Normal Women With Alzheimer’S Disease Proteinopathy Show Relative Preservation Of Memory But Not Of Hippocampal Volume, Jessica Z.K. Caldwell, Jeffrey L. Cummings, Sarah J. Banks, Sebastian Palmqvist, Oskar Hansson

School of Medicine Faculty Publications

Background: We examined interactive effects of sex, diagnosis, and cerebrospinal fluid (CSF) amyloid beta/phosphorylated tau ratio (Aβ/P-tau) on verbal memory and hippocampal volumes. Methods: We assessed 682 participants (350 women) from BioFINDER (250 cognitively normal [CN]; and 432 symptomatic: 186 subjective cognitive decline [SCD], 246 mild cognitive impairment [MCI]). General linear models evaluated effects of Alzheimer’s disease (AD) proteinopathy (CSF Aß/p-tau ratio), diagnosis, and sex on verbal memory (ADAS-cog 10-word recall), semantic fluency (animal naming fluency), visuospatial skills (cube copy), processing speed/attention functions (Symbol Digit Modalities Test and Trail Making Part A), and hippocampal volumes ...


Intralingual And Intrapleural Aav Gene Therapy Prolongs Survival In A Sod1 Als Mouse Model, Allison M. Keeler, Marina Zieger, Carson Semple, Logan Pucci, Alessandra Veinbachs, Robert H. Brown Jr., Christian Mueller, Mai K. Elmallah 2019 University of Massachusetts Medical School

Intralingual And Intrapleural Aav Gene Therapy Prolongs Survival In A Sod1 Als Mouse Model, Allison M. Keeler, Marina Zieger, Carson Semple, Logan Pucci, Alessandra Veinbachs, Robert H. Brown Jr., Christian Mueller, Mai K. Elmallah

Pediatric Publications

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that results in death from respiratory failure. No cure exists for this devastating disease, but therapy that directly targets the respiratory system has the potential to prolong survival and improve quality of life in some cases of ALS. The objective of this study was to enhance breathing and prolong survival by suppressing superoxide dismutase 1 (SOD1) expression in respiratory motor neurons using adeno-associated virus (AAV) expressing an artificial microRNA targeting the SOD1 gene. AAV-miR(SOD1) was injected in the tongue and intrapleural space of SOD1(G93A) mice, and repetitive respiratory and ...


Characterization Of The Effect Of Exercise Dose And Integrative Nonpharmacological Therapies In The Treatment Of Chronic Pain, Anna M. Polaski 2019 Duquesne University

Characterization Of The Effect Of Exercise Dose And Integrative Nonpharmacological Therapies In The Treatment Of Chronic Pain, Anna M. Polaski

Electronic Theses and Dissertations

Chronic pain includes debilitating conditions affecting large populations of people throughout the world. These diseases are further complicated by comorbid psychological disorders which make chronic pain conditions difficult to treat. Nonpharmacological treatment options have more recently become an important mainstay of effective therapies and are currently being used to supplement or replace traditional pharmacological treatment methods. Exercise-based therapies in particular are of interest due to their demonstrated success in reducing pain symptoms as well as improving psychological outcomes. Dose is an important factor in being able to effectively prescribe treatments in the context of specific exercise interventions and specific pain ...


Nanomedicine-Driven Neuropathic Pain Relief In Rat Model Is Associated With Macrophage Polarity And Mast Cell Activation, Muzamil Saleem 2019 Duquesne University

Nanomedicine-Driven Neuropathic Pain Relief In Rat Model Is Associated With Macrophage Polarity And Mast Cell Activation, Muzamil Saleem

Electronic Theses and Dissertations

We explored the immune neuropathology underlying multi-day relief from neuropathic pain in a rat model initiated at the sciatic nerve by using a nanoemulsion-based nanomedicine as a biological probe. The nanomedicine is theranostic: both therapeutic (containing celecoxib drug) and diagnostic (containing near-infrared fluorescent (NIRF) dye) and is small enough to be phagocytosed by circulating monocytes. A model of neuropathic pain is initiated by tying four 1mm spaced knots around the sciatic nerve with chromic gut suture, which results in neuroinflammation, and a resultant pain-like behavior manifests. We show that pain-like behavior reaches a plateau of maximum hypersensitivity 8 days post-surgery ...


Towards A Unified Disease Mechanism For Trna Synthetase-Mediated Peripheral Neuropathy, Emily L. Spaulding 2019 The Jackson Laboratory

Towards A Unified Disease Mechanism For Trna Synthetase-Mediated Peripheral Neuropathy, Emily L. Spaulding

Electronic Theses and Dissertations

Charcot-Marie-Tooth disease (CMT) is a debilitating inherited peripheral neuropathy resulting in progressive distal muscle atrophy and loss of sensation. CMT is genetically heterogeneous, with mutations in over 80 different genes leading to demyelinating or axonal forms. There are genetically similar subgroups, including the largest protein family implicated in the disease, the tRNA synthetases (ARSs). ARSs are responsible for aminoacylation of tRNAs during translation and are therefore ubiquitously expressed and essential proteins. Dominant mutations in at least five ARSs cause axonal forms of CMT. How mutations in ARSs cause CMT is unclear, however, the similar clinical presentation of patients suggests shared ...


Combining Multi-Omics And Drug Perturbation Profiles To Identify Novel Treatments That Improve Disease Phenotypes In Spinal Muscular Atrophy, Katharina Meijboom, Viola Volpato, Jimena Monzón-Sandoval, Joseph M. Hoolachan, Suzan M. Hammond, Frank Abendroth, Olivier Gerrit de Jong, Gareth Hazell, Nina Ahlskog, Matthew J.A. Wood, Caleb Webber, Melissa Bowerman 2019 University of Massachusetts Medical School

Combining Multi-Omics And Drug Perturbation Profiles To Identify Novel Treatments That Improve Disease Phenotypes In Spinal Muscular Atrophy, Katharina Meijboom, Viola Volpato, Jimena Monzón-Sandoval, Joseph M. Hoolachan, Suzan M. Hammond, Frank Abendroth, Olivier Gerrit De Jong, Gareth Hazell, Nina Ahlskog, Matthew J.A. Wood, Caleb Webber, Melissa Bowerman

University of Massachusetts Medical School Faculty Publications

Spinal muscular atrophy (SMA) is a neuromuscular disorder caused by loss of survival motor neuron (SMN) protein. While SMN restoration therapies are beneficial, they are not a cure. We aimed to identify novel treatments to alleviate muscle pathology combining transcriptomics, proteomics and perturbational datasets. This revealed potential drug candidates for repurposing in SMA. One of the lead candidates, harmine, was further investigated in cell and animal models, improving multiple disease phenotypes, including SMN expression and lifespan. Our work highlights the potential of multiple, parallel data driven approaches for development of novel treatments for use in combination with SMN restoration therapies.


Genetic Taster Status As A Mediator Of Neural Activity And Swallowing Mechanics In Healthy Adults, Angela M. Dietsch, Ross M. Westemeyer, William G. Pearson Jr., Douglas H. Schultz 2019 University of Nebraska–Lincoln

Genetic Taster Status As A Mediator Of Neural Activity And Swallowing Mechanics In Healthy Adults, Angela M. Dietsch, Ross M. Westemeyer, William G. Pearson Jr., Douglas H. Schultz

Center for Brain, Biology and Behavior: Papers & Publications

As part of a larger study examining relationships between taste properties and swallowing, we assessed the influence of genetic taster status (GTS) on measures of brain activity and swallowing physiology during taste stimulation in healthy men and women. Twenty-one participants underwent videofluoroscopic swallowing study (VFSS) and functional magnetic resonance imaging (fMRI) during trials of high-intensity taste stimuli. The precisely formulated mixtures included sour, sweet-sour, lemon, and orange taste profiles and unflavored controls. Swallowing physiology was characterized via computational analysis of swallowing mechanics plus other kinematic and temporal measures, all extracted from VFSS recordings. Whole-brain analysis of fMRI data assessed blood ...


Assessing The Morphology Of Vesicles In Inhibitory Symmetric Synapses In Safety And Fear Conditions In The Rat Lateral Amygdala, Valerie Kress 2019 University of Connecticut

Assessing The Morphology Of Vesicles In Inhibitory Symmetric Synapses In Safety And Fear Conditions In The Rat Lateral Amygdala, Valerie Kress

Honors Scholar Theses

There is a significant lack of research on vesicle morphology in inhibitory synapses in the rat lateral amygdala. Published research focuses heavily on excitatory synapses in different parts of the rat brain and even this research rarely focuses on the different vesicle types in axons. It is reported that in these axons, synaptic vesicles traditionally contain neurotransmitters while small dense core vesicles contain active zone proteins and large dense core vesicles contain neuropeptides. This study aims to find correlations between vesicle morphology, location, contents, and potential function of each of the different types of vesicle in inhibitory axons.

After reviewing ...


A Microfluidic Platform To Investigate The Mechanism By Which Gdnf Overexpression In Schwann Cells Causes Neuronal Axon Entrapment, Ze Zhong Wang 2019 Washington University in St. Louis

A Microfluidic Platform To Investigate The Mechanism By Which Gdnf Overexpression In Schwann Cells Causes Neuronal Axon Entrapment, Ze Zhong Wang

Engineering and Applied Science Theses & Dissertations

Twenty million Americans suffer from peripheral nerve injury (PNI) caused by trauma and medical disorders, with approximately $150 billion spent in annual health-care dollars in the United States. Even with proper surgical reconstruction, less than 50% of the patients achieve satisfactory functional recovery. The gold standard surgical repair for long gaps (>3cm) is the autologous nerve graft, despite its disadvantages such as donor site morbidity, risk of infection, and increased cost. Alternative methods, such as acellular nerve grafts (ANA), are ineffective for large lesion gaps because of the lack of cells and regeneration factors. Recent efforts have been focused on ...


Genomic Contributors To Individual Differences In Reward-Related Neural Activity, Lindsay Jane Michalski 2019 Washington University in St. Louis

Genomic Contributors To Individual Differences In Reward-Related Neural Activity, Lindsay Jane Michalski

Arts & Sciences Electronic Theses and Dissertations

Aberrant reward-related behavior, including impulsive and risk-taking behaviors, is a common feature of externalizing psychopathology (e.g., attention deficit hyperactivity disorder, antisocial personality disorder, and substance-use disorders). Through imaging studies, these behaviors have been linked to dysregulated reactivity within a diffuse reward-related corticostriatal neural network, including the striatum, frontal regions (namely orbital, ventromedial, and dorsolateral cortices), the insula, and the hippocampus. Because variability in risk-taking behavior and related psychopathology is moderately-to-largely heritable (i.e., with estimates ranging from 40 – 80%), a genetically-informed approach is well-positioned to provide valuable insight into the etiology of reward-related neural and behavioral phenotypes that characterize ...


The Role Of Adult Hippocampal Neurogenesis In Depression-Relevant Reward-Related Behaviours, Katrina Zmavc 2019 The University of Western Ontario

The Role Of Adult Hippocampal Neurogenesis In Depression-Relevant Reward-Related Behaviours, Katrina Zmavc

Electronic Thesis and Dissertation Repository

The variability in the symptomatology of depressive disorders and antidepressant treatment response has led to an increased interest in the molecular, cellular, and circuit mechanisms of many aspects of affect. Evidence suggests a reduction in adult hippocampal neurogenesis (AHN) is associated with an increase in depression-like behaviour, though much of this evidence has been from studies using aversive tests (e.g., forced swim test). Here, I used touchscreen operant chambers, which allow for non-aversive and translational testing, to test the hypothesis that AHN plays a contributing role in emotion regulation. A panel of three touchscreen tests were chosen to assess ...


Alzheimer's And Amyloid Beta: Amyloidogenicity And Tauopathy Via Dyshomeostatic Interactions Of Amyloid Beta, Jordan Tillinghast 2019 Liberty University

Alzheimer's And Amyloid Beta: Amyloidogenicity And Tauopathy Via Dyshomeostatic Interactions Of Amyloid Beta, Jordan Tillinghast

Senior Honors Theses

This paper reviews functions of Amyloid-β (Aβ) in healthy individuals compared to the consequences of aberrant Aβ in Alzheimer’s disease (AD). As extraneuronal Aβ accumulation and plaque formation are characteristics of AD, it is reasonable to infer a pivotal role for Aβ in AD pathogenesis. Establishing progress of the disease as well as the mechanism of neurodegeneration from AD have proven difficult (Selkoe, 1994). This thesis provides evidence suggesting the pathogenesis of AD is due to dysfunctional neuronal processes involving Aβ’s synaptic malfunction, abnormal interaction with tau, and disruption of neuronal homeostasis. Significant evidence demonstrates that AD symptoms ...


The Dolphin Brain - A Digital Presentation, Laura Taylor, Cally Gurley, Samia Pratt, David Mokler 2019 University of New England

The Dolphin Brain - A Digital Presentation, Laura Taylor, Cally Gurley, Samia Pratt, David Mokler

Biomedical Sciences Faculty Projects

This digital presentation has been reproduced from the 2019 University of New England Ketchum Gallery exhibition of original artwork, scientific data, and materials from the Peter J. Morgane Research Collection on the Cetacean Brain, 1962-2004.


Effects Of Mercury On The Dopamine Transporter Cell Surface Expression In Pc12 Cells, Christina Hui 2019 CUNY John Jay College

Effects Of Mercury On The Dopamine Transporter Cell Surface Expression In Pc12 Cells, Christina Hui

Student Theses

Environmental factors, such as heavy metal exposures, have been suggested to have an impact not only on neurodegenerative disease, such as Parkinson’s disease, but also on psychostimulants abuse and their toxicity. In this study, two questions were addressed: 1) effects of mercuric chloride on parkinsonian toxicant 1-methyl-4-phenylpyridinium (MPP+) induced cytotoxicity and 2) effects of mercuric chloride on cell surface dopamine transporter. Pheochromocytorma cells (PC12) were treated with various concentrations of mercuric chloride (0.02~2.0 ppm) for 4 hours with and without 0.1 mM MPP+. Significant potentiation of toxicity was observed when there was co-treatment with 0 ...


Computational Neuroscience, Michelle Greene, NS/PY 357 Students 2019 Bates College

Computational Neuroscience, Michelle Greene, Ns/Py 357 Students

Open Educational Resources

In Fall 2019, the Computational Neuroscience class at Bates College collaborated to begin an open textbook. Eight students across three majors collaborated to present the content they were learning to students who were similar to themselves. This project serves both pedagogical and social goals. By writing for fellow students, we leveraged the power of teaching for learning. By bringing together students of diverse academic backgrounds, we leveraged the power of peer instruction. Finally, by writing in the open, students not only brought their best work forward, but are working to contribute to an open knowledge environment that democratizes information. This ...


The Feedback-Related Negativity Is A Time-Dependent Brain Mechanism That Facilitates Aversive Learning: Implications For The Reinforcement Learning Frn Hypothesis, Eric Rawls 2019 University of Arkansas, Fayetteville

The Feedback-Related Negativity Is A Time-Dependent Brain Mechanism That Facilitates Aversive Learning: Implications For The Reinforcement Learning Frn Hypothesis, Eric Rawls

Theses and Dissertations

Organisms encode rewarding and aversive experiences through reinforcement learning, capitalizing on prediction errors (PEs), which adapt action strategies over time. Computational theories are explicit that PE signals should update action weights continuously over the course of a behavioral task, an important time-dependent variation that is eschewed in traditional neuroscience studies that average over large numbers of trials. I examined variation in reaction times and feedback-locked cortical activity over time as a function of PE to critically examine theories indicating that PE signals drive time-dependent learning. We recorded EEG while participants completed a novel reinforcement task that varied prediction error on ...


Functional Dissociations Revealed By Representational Similarity Analysis Of Color-Word Stroop, Michael Freund 2019 Washington University in St. Louis

Functional Dissociations Revealed By Representational Similarity Analysis Of Color-Word Stroop, Michael Freund

Arts & Sciences Electronic Theses and Dissertations

The color-word Stroop task is often used in cognitive neuroscience as a common platform for both theoretical and experimental approaches to cognitive control. Yet traditionally, there has been tension between these two approaches. Theoretical models of Stroop have focused on representation: for example, how distributed and overlapping representations of the two stimulus dimensions (color, word) are prioritized, and how conflict between these dimen- sions is represented and used to regulate control. In contrast, neuroimaging experiments have primarily focused on ‘univariately’ (uniformly) mapping the effects of conflict to par- ticular brain regions. This focus on univariate changes in brain activity limits ...


Understanding Object Motion Encoding In The Mammalian Retina., Victor Julian DePiero 2019 University of Louisville

Understanding Object Motion Encoding In The Mammalian Retina., Victor Julian Depiero

Electronic Theses and Dissertations

Phototransduction, transmission of visual information down the optic nerve incurs delays on the order of 50 – 100ms. This implies that the neuronal representation of a moving object should lag behind the object’s actual position. However, studies have demonstrated that the visual system compensates for neuronal delays using a predictive mechanism called phase advancing, which shifts the population response toward the leading edge of a moving object’s retinal image. To understand how this compensation is achieved in the retina, I investigated cellular and synaptic mechanisms that drive phase advancing. I used three approaches, each testing phase advancing at a ...


Functional Analysis In The Home Setting Of An Older Adult With Neurocognitive Disorder, Emily Norton 2019 Western Michigan University

Functional Analysis In The Home Setting Of An Older Adult With Neurocognitive Disorder, Emily Norton

Master's Theses

Currently within the behavioral gerontology literature there are no published studies that include a functional assessment in the home setting. The primary goal of the present study was to address this gap by conducting a functional analysis on a challenging behavior of an older adult with neurocognitive disorder in the home. This study occurred in two phases. During phase one, researchers conducted an antecedent functional analysis on the bizarre speech of an 81-year-old female with suspected dementia across four conditions (television on, no interactions initiated; television on, interactions initiated; television off, no interactions initiated; television off, interactions initiated). Results from ...


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