Neurosciences Commons^™

Crispr-Krispr: A Method To Identify On-Target And Random Insertion Of Donor Dnas And Their Characterization In Knock-In Mice, Masayuki Tanaka, Keiko Yokoyama, Hideki Hayashi, Sanae Isaki, Kanae Kitatani, Ting Wang, Hisako Kawata, Hideyuki Matsuzawa, Channabasavaiah B. Gurumurthy, Hiromi Miura, Masato Ohtsuka

Journal Articles: Pharmacology & Experimental Neuroscience

CRISPR tools can generate knockout and knock-in animal models easily, but the models can contain off-target genomic lesions or random insertions of donor DNAs. Simpler methods to identify off-target lesions and random insertions, using tail or earpiece DNA, are unavailable. We develop CRISPR-KRISPR (CRISPR-Knock-ins and Random Inserts Searching PRotocol), a method to identify both off-target lesions and random insertions. CRISPR-KRISPR uses as little as 3.4 μg of genomic DNA; thus, it can be easily incorporated as an additional step to genotype founder animals for further breeding.

Ecdysoneless Overexpression Drives Mammary Tumorigenesis Through Upregulation Of C-Myc And Glucose Metabolism, Bhopal C. Mohapatra, Sameer Mirza, Aditya Bele, Channabasavaiah B. Gurumurthy, Mohsin Raza, Irfana Saleem, Matthew D. Storck, Aniruddha Sarkar, Sai Sundeep Kollala, Surendra K. Shukla, Siddesh Southekal, Kay-Uwe Wagner, Fang Qiu, Subodh M. Lele, Mansour A. Alsaleem, Emad A. Rakha, Chittibabu Guda, Pankaj K. Singh, Robert D. Cardiff, Hamid Band, Vimla Band

Journal Articles: Pharmacology & Experimental Neuroscience

Ecdysoneless (ECD) protein is essential for embryogenesis, cell-cycle progression, and cellular stress mitigation with an emerging role in mRNA biogenesis. We have previously shown that ECD protein as well as its mRNA are overexpressed in breast cancer and ECD overexpression predicts shorter survival in patients with breast cancer. However, the genetic evidence for an oncogenic role of ECD has not been established. Here, we generated transgenic mice with mammary epithelium-targeted overexpression of an inducible human ECD transgene (ECDTg). Significantly, ECDTg mice develop mammary hyperplasia, preneoplastic lesions, and heterogeneous tumors with occasional lung metastasis. ECDTg tumors exhibit epithelial to mesenchymal transition …

Efficacy Of Prebiotic Dietary Intervention To Mitigate Risks For Dementia Via The Gut-Brain Axis, Lucille M. Yanckello

Theses and Dissertations--Pharmacology and Nutritional Sciences

Alzheimer’s disease (AD) is the most common form of dementia with various risk factors including age, environmental factors such as brain injury and genetic factors, such as the E4 allele of the Apolipoprotein gene. Presence of the APOE4 allele increases AD risk by two- to four- fold. Recent studies have shown that mild traumatic brain injury (mTBI), even without loss of consciousness, increases risk of dementia diagnosis by more than two-fold in military personnel and is also a significant environmental risk factor for developing dementia in the general population. The gut-brain axis (GBA) or bi-directional communication between the brain and …

The Role Of Socioeconomic Status In Cognition And Brain Health Across The Lifespan, Erica Chung

Honors Theses

Disparities in cognition are inevitable throughout the lifespan due to socioeconomic gaps. Individuals of lower socioeconomic status (SES) may have fewer access to environmental resources, especially with regard to education, than individuals of higher socioeconomic status. Differences in available resources from a young age may affect brain development, leading to detriments in cognition and behavior, further impacting socioeconomic success in adulthood. In the present study, we modeled the development of the dorsolateral prefrontal cortex (DLPFC) and changes in cognitive function throughout the life trajectory in the Nathan Kline Institute for Psychiatric Research Rockland Sample. The DLPFC volume was predicted to …

The Anorexic Effect Of Dl-Fenfluramine Is Dependent On Animals' Habituation To Different Food Types, Sun Shin Yi, Sujean Choi

Biomedical Sciences Faculty Research and Publications

Background: As rates of obesity and diabetes have increased dramatically over the past few decades, the use of anti-obesity drugs has now become a routine therapeutic measure. However, the pharmacological effects of chronic use of these drugs in humans frequently lead to reduced efficacy in reducing appetite and body weight through as-yet-unidentified mechanisms. An example of this can be found in animal studies where the appetite suppressant DL-fenfluramine (FEN) is chronically administered and its tolerance develops in animals and humans. The appetite effects of FEN are typically measured in several animal studies by the feeding changes in a balanced standard …

A Study Of Limited Bedding And Nesting On Maternal Behavior For Postpartum Depression, Emma Brezoczky

CMC Senior Theses

Postpartum depression (PPD) affects up to 20% of mothers in the US and can detrimentally affect both the mother and psychosocial development of the child (Pearlstein et al, 2009). So far, research on PPD is limited and the underlying neuropathology remains unclear. Low socioeconomic status is one risk factor that increases the risk of PPD tenfold (Goyal et al, 2010). The low resource limited bedding and nesting (LBN) paradigm used for rodents has the potential to model this risk factor. LBN has not previously been studied with PPD, but observations of disrupted maternal behaviors and depressive phenotypes makes it a …

Effects Of The Selective Gsk3b Inhibitor, Tideglusib, On Ethanol Consumption, Anxiety-Like Behavior, Taste Preference, And Downstream Proteins, Sam Gottlieb, Douglas Bledsoe, Jessica L. Maltman, Alanna Morgan, Jennifer T. Wolstenholme, Michael F. Miles

Graduate Research Posters

Background: We have shown modulations in glycogen synthase kinase 3 beta (GSK3B) abundance or activity regulate ethanol consumption, suggesting potential as a therapeutic target for alcohol use disorder (AUD). Here we report the GSK3B inhibitor tideglusib’s actions on ethanol consumption, basal behaviors, and modulation of GSK3B targets.

Methods: C57BL/6J males and females received i.g. 200mg/kg tideglusib, except drinking-in-the-dark (males;100mg/kg i.p.). Drinking-in-the-dark (DID): Mice given 20% ethanol 4-hours, 4-days/week x 3 weeks and then i.p. tideglusib or vehicle x 4 days in a Latin Square design with ethanol consumption measured daily. Light/Dark Box: Mice gavaged with tideglusib or vehicle …

Mental Disorders, The Positivity Effect, And Questions Of Identity And Responsibility, Liam Jones

Pitzer Senior Theses

In order to judge how behavior caused by the positivity effect should be considered, comparisons were made between the positivity effect and two mental disorders. These disorders, Tourette’s syndrome and psychopathy, were selected due to their extreme differences in what Strawsonian attitudes they inspire and how they are perceived relative to disordered patients’ will. Disorder-affected behavior of Tourette’s patients inspires the objective attitude and is seen as a condition affecting an individual’s will, while disorder-affected behavior of psychopaths inspires the interpersonal attitude and is seen as a character trait. Relevant distinctions between psychopathy and Tourette’s syndrome were found to include …

The Effect Of Young Blood Anti-Aging Treatment On Protein Markers Of Age And Huntington Disease, Sujena H. Koilpillai

Honors Undergraduate Theses

Huntington disease (HD) is a neurodegenerative disorder caused by expansion of a polyglutamine tract within the huntingtin (HTT) protein, forming mutant HTT (mtHTT). HD patients suffer from psychiatric, behavioral, cognitive, and motor abnormalities, with death typically occurring 15-20 years after symptom onset. Currently, there are no treatments able to slow disease progression or delay onset. HD is a disease of aging. Despite the mtHTT protein being produced throughout life, symptoms do not typically appear until adulthood. Furthermore, many cellular effects of normal aging are also seen in HD, including altered intercellular communication and loss of proteostasis. Recently, our lab found …

Investigating The Effects Of In-Vivo Therapeutics Hypoxia Treatment Paradigms In Neurite Outgrowth Patterns, Jae Hyun Yoo

Theses and Dissertations--Medical Sciences

Spinal cord injury, specifically in the cervical C3-C4 region of the cervical spine, contributes to impaired breathing and a diminished quality of life. Therefore it is important to find effective and safe therapeutics to restore breathing function. Indeed, there are a myriad of research being performed in addition to valuable collaboration amongst different institutions. As such, inspired by a previous experiment, we decided to test our hypothesis that an enriching environment consisting of different hypoxic environments - sustained and intermittent hypoxia alongside normoxia - would result in neurite outgrowth. Moreover, we hypothesized that sustained hypoxia would result in the greatest …

Mammalian Target Of Rapamycin Cell Signaling Pathway In Phosphatase And Tensin Homolog Induced Kinase 1 Knockout Rat Model Of Familial Parkinson's Disease, Martha Helena Mortell

Theses and Dissertations--Medical Sciences

More than 10 million people are living with Parkinson’s disease (PD), one million of which are people in the United States. PD is the second most common age-related neurodegenerative disorder, after Alzheimer’s disease, and is characterized by the accumulation of a-synuclein aggregates and the degeneration of dopaminergic neurons. The loss of endogenous dopamine in PD brain accounts for the motor decline presented clinically in PD patients. Etiological factors of PD include oxidative damage and inflammation, although the detailed mechanisms remain unknown. Risk factors for PD include gender, age, environmental factors, and gene mutations.

The current thesis research employed phosphatase and …

Evaluating The Microbiome To Boost Recovery From Stroke: The Embrs Study, Tyler Hammond

Theses and Dissertations--Neuroscience

Accumulating evidence suggests that gut microbes modulate brain plasticity via the bidirectional gut-brain axis and may play a role in stroke rehabilitation. A severely imbalanced microbial community has been shown to occur following stroke, causing a systemic flood of neuro- and immunomodulatory substances due to increased gut permeability and decreased gut motility. Here we measure post-stroke increased gut dysbiosis and how it correlates with gut permeability and subsequent cognitive impairment.

We recruited 12 participants with acute stroke, 12 healthy control participants, and 18 participants who had risk factors for stroke, but had not had a stroke. We measured the gut …

Evaluating The Role Of Mmp9 In Hyperhomocysteinemia Induced Cerebrovascular Pathology, Alexandria Linton

Theses and Dissertations--Neuroscience

Vascular contributions to cognitive impairment and dementia (VCID) is one of the leading causes of dementia, along with Alzheimer’s disease (AD), and often manifests as a comorbidity of AD. Elevated plasma homocysteine, known as hyperhomocysteinemia (HHcy), is a risk factor for VCID; however, the mechanism underlying the connection between HHcy and development of VCID pathology remains elusive. Understanding this mechanism would reveal novel therapeutic targets with the potential to be disease modifying, which are a critical need for a disease that lacks any approved treatment. Previous studies from our lab have strongly associated neuroinflammation and blood brain barrier (BBB) dysregulation …

Uncovering The Role Of Apoe4 On Alzheimer’S Disease-Related Neuroinflammation, Courtney Marie Kloske

Theses and Dissertations--Physiology

Alzheimer’s disease (AD) is the most common neurodegenerative disease and is characterized by two hallmark pathologies: amyloid-beta plaques (Ab plaques) and hyperphosphorylated, aggregated tau tangles. These pathologies are typically accompanied by the presence of neuroinflammation which is primarily mediated by microglia. Interestingly, several genetic risk factors that increase the risk of AD also have direct impacts on neuroinflammation. Of interest, Apolipoprotein E (ApoE) is the largest genetic risk factor for AD. ApoE has three isoforms- E4 confers an increased risk for AD, E3 is considered the “control” phenotype, and E2 is protective against AD. E4 plays a role in virtually …

Evaluating The Relationship Between Plasma Biomarkers And Dementia Using Hierarchical Clustering Analysis And Linear Modeling, Zachary Winder

Theses and Dissertations--Physiology

Dementia is a disorder characterized by a significant decline from baseline in one or more cognitive domains that interferes with independence. Prevalence of dementia worldwide is estimated at 50 million people, with that number expected to triple by 2030, coming with a cost of roughly $2 trillion. Clinically, dementia is diagnosed using cognitive evaluations, with varying domains affected and to different degrees depending on the underlying pathology and stage of disease. Alzheimer’s disease (AD) and vascular contributions to cognitive impairment and dementia (VCID) are the two leading causes of dementia, and both have pathologies which can be visualized using MRI. …

Chronic Low Back Pain In Veterans And The Role Of Yoga: An Overview Of Randomized Controlled Trials, Suresh Kumar Thanneeru, Roshan Chanchlani, Pramod K. Sharma, Sudarsan Agarwal, Nalla Srinivas, M Sukumar, Amit Agrawal

Manipal Journal of Medical Sciences

Introduction One of the most debilitating diseases in elderly is the chronic low back pain (cLBP) which is most often nonspecific and involves using unrelenting medication and physical therapy. Yoga practice has been explored to treat this condition and was shown good results. This systematic review was done to emphasis the role of Yoga in management of cLBP. Objectives To evaluate the effectiveness of Yoga in pain relief and improvement in disability for veterans suffering from cLBP. Methods A systematic search was conducted on PubMed, Scopus, ScienceDirect, and Cochrane to identify studies on usage of Yoga in the treatment of …

Identifying Key Elements To Assess Patient’S Acceptability Of Neurorehabilitation In Stroke Survivors–A Delphi Method, Manonita Ghosh, Kaoru Nosaka, Lisa Whitehead, Kazunori Nosaka

Research outputs 2014 to 2021

Purpose: Assessing patient acceptability of treatment is a clinical concern. No guidance exists to determine the best way to measure acceptability in stroke neurorehabilitation. This study identifies key elements to measure patient’s acceptance of stroke neurorehabilitation by establishing expert consensus.

>Materials and methods: A four-phase Delphi method with a three-round electronic-based survey was conducted. Experts were considered as stroke survivors or their caregivers and professionals in stroke neurorehabilitation. A twenty-five-item list was sourced from a literature review and discussion with a consumer panel (n = 22). In Round-1 (n = 118) and Round-2 (n = 80), experts …

Influences Of Disrupted Circadian Rhythms On Stroke Outcome, Jennifer A. Liu

Graduate Theses, Dissertations, and Problem Reports (ETD)

The circadian system is composed of a subset of temporal oscillators that function through a transcriptional and post-translational molecular and functional negative feedback loop cycling approximately every 24 hours. The central clock located in the suprachiasmatic nucleus is responsible for entrainment using light as the key timekeeper (zeitgeber); it is responsible for synchronizing and optimizing physiological behavior and function to the environment. Exogenous information, such as day length and light-dark cycles, provide critical temporal cues for adjusting to environmental conditions. Proper alignment to natural light dark cycles and circadian rhythms is optimal for vital health, fitness, and survival in organisms. …

Patients’ Experiences Of A Communication Enhanced Environment Model On An Acute/Slow Stream Rehabilitation And A Rehabilitation Ward Following Stroke: A Qualitative Description Approach, Sarah D'Souza, Deborah J. Hersh, Erin Godecke, Natalie Ciccone, Heidi Janssen, Elizabeth Armstrong

Research outputs 2014 to 2021

Background

Patients in hospital following stroke express a desire to continue therapy tasks outside of treatment activities. However, they commonly describe experiences of boredom and inactivity. An enriched environment aims to provide opportunities for physical, cognitive and social activity and informed the development of a Communication Enhanced Environment (CEE) model to promote patient engagement in language activities.

Purpose

Explore patient perceptions of a CEE model, and barriers and facilitators to engagement in the model.

Methods

A qualitative description study from a larger project that implemented a CEE model into acute and rehabilitation private hospital wards in Western Australia. Semi-structured interviews …

Protocol For The Development Of The International Population Registry For Aphasia After Stroke (I-Praise), M. Ali, A. L. Ben Basat, M. Berthier, M. B. Johansson, C. Breitenstein, D. A. Cadilhac, F. Constantinidou, M. Cruice, G. Davila, M. Gandolfi, M. Gil, R. Grima, Erin Godecke, L. Jesus, L. M. Jiminez, M. Kambanaros, T. Kukkonen, A. Laska, I. Mavis, R. Mc Menamin, C. Mendez-Orellana, H. Obrig, P. Ostberg, H. Robson, K. Sage, M. Van De Sandt-Koenderman, K. Sprecht, E. Visch-Brink, E. Wehling, S. Wielaert, S. J. Wallace, L. J. Williams, M. C. Brady

Research outputs 2014 to 2021

Background: We require high-quality information on the current burden, the types of therapy and resources available, methods of delivery, care pathways and long-term outcomes for people with aphasia. Aim: To document and inform international delivery of post-stroke aphasia treatment, to optimise recovery and reintegration of people with aphasia. Methods & Procedures: Multi-centre, prospective, non-randomised, open study, employing blinded outcome assessment, where appropriate, including people with post-stroke aphasia, able to attend for 30 minutes during the initial language assessment, at first contact with a speech and language therapist for assessment of aphasia at participating sites. There is no study-mandated intervention. Assessments …

Autonomous And Non-Autonomous Requirements For The C-Jun N-Terminal Kinase Signaling Pathway In Early Forebrain Development, Jessica G. Cunningham

Graduate Theses, Dissertations, and Problem Reports (ETD)

The cerebral cortex is responsible for a wide variety of high-level functions including cognition, sensory perception, fine motor control, and the orchestration of body movements. The cortex is comprised of cortical excitatory neurons and inhibitory interneurons, which are arranged in a highly organized fashion into different layers and regions. These two types of cells operate in a delicate balance between excitation and inhibition, which is critical for proper cortical circuitry. In order for the cortex to execute its numerous functions, it must both send and receive input to other brain regions through axonal connections. The organization within the cortex and …

Theta Burst Brain Stimulation In Painful Diabetic Neuropathy Patients: Investigating Neural Mechanisms, Bhushan Thakkar

Theses and Dissertations

Chronic pain (CP) is a significant contributor to disability and disease burden globally. In 2019, approximately 50.2 million adults (20.4% of the US population) experienced chronic pain, contributing to $560-635 billion in direct medical costs. In addition, the worldwide prevalence of diabetes mellitus has reached epidemic proportions and is set to increase to 629 million by 2045. Almost 50% of patients with diabetes present with diabetic neuropathy (DN), and one in five patients with diabetes presents with painful DN (pDN) which is the most common cause of neuropathic pain (NP) in the US. Symptomatic treatment is the mainstay of management …

Defining Patient Cohorts For Guiding Clinical Trials And Treatment In Lafora Disease: A Model For The Rare Disease Community, Katherine Janae Donohue

Theses and Dissertations--Molecular and Cellular Biochemistry

In the US, approximately 8000 rare diseases have been identified. Combined, rare diseases impact more than 30 million people in the U.S. alone, with 75% of those being children. However, research, funding, and therapeutic development for the rare disease community remains challenging because of the incredible diversity – not only between diseases, but often even within a single disease.

LD is an ultra-rare childhood dementia and epilepsy caused by mutations in one of two driver genes: EPM2A, which encodes for the glycogen phosphatase laforin, and EPM2B/NHLRC1, which encodes the E3 ubiquitin ligase malin. Children with LD …

Multi-Center, Single-Blind Randomized Controlled Trial Comparing Functional Electrical Stimulation Therapy To Conventional Therapy In Incomplete Tetraplegia, Kim D Anderson, Radha Korupolu, Kristin E Musselman, Jacqueline Pierce, James R Wilson, Nuray Yozbatiran, Naaz Desai, Milos R Popovic, Lehana Thabane

Faculty, Staff and Student Publications

BACKGROUND: Loss of upper extremity function after tetraplegia results in significant disability. Emerging evidence from pilot studies suggests that functional electrical stimulation (FES) therapy may enhance recovery of upper extremity function after tetraplegia. The aim of this trial was to determine the effectiveness of FES therapy delivered by the Myndmove stimulator in people with tetraplegia.

METHODS: A multi-center

RESULTS: Between June 2019 to August 2021, 51 participants were randomized to FES (

CONCLUSION: Forty sessions of FES therapy delivered by the MyndMove stimulator are as effective as conventional therapy in producing meaningful functional improvements that persist after therapy is completed. …

Early Life Stress Inoculation Effects On Adult Behaviors, Oreoluwa Ibukunolupo Akinbo

Graduate Research Theses & Dissertations

Chronic and acute stressors are implicated in mental illnesses such as depression, anxiety and posttraumatic disorder. These adulthood disorders may be influenced by stressor exposure during early life. However, controlled mild stressors are linked to the building of resiliency towards later intense stressors. Previously, rodent models have been used to investigate the resilience-promoting effects of early life stress inoculation protocols. For example, the presentation of mild stressors (such as an experimenter handling a rodent for brief periods of time) or exposure to environmental enrichment (such as a presenting a variety of items and activities in the home cage of a …

Investigating The Influence Of Stress On Motivational Dysfunction In Male And Female Rodents, Emily Laine Errante

Graduate Research Theses & Dissertations

Motivational dysfunction is present in a variety of disorders, including major depressive disorder, schizophrenia, and Parkinsonism and can negatively impact social functioning, employment, and treatment response. Interestingly, outside stressors and stress hormones have been shown to contribute to depressive episodes in humans and depressive-like behaviors in rodents, including reducing motivated behaviors. Effort-related decision making procedures have been utilized in both humans and animals in order to examine motivational dysfunction, as it offers a subject a choice between high effort/reward and low effort/reward options, but little research has examined the effects of stress on effort-related decision making behaviors. Moreover, almost all …

Dissociating Sensorimotor And Posterior Parietal Contributions To Fine Motor Control In Female And Male Mice, Jenna Rae Osterlund Oltmanns

Graduate Research Theses & Dissertations

Fine motor control is a beneficial adaptation animals have developed. This ability allows animals to traverse difficult terrain, manipulate food, build shelter, and handle tools. Loss of fine motor control occurs in half of patients that survive stroke, a devastating neurological event affecting 15 million people annually. While many patients experience spontaneous recovery in the first month following stroke, about half of stroke survivors remain permanently disabled. Though medical advancements have increased survival rates, stroke remains a leading and rising cause of disability. There has been only one pharmaceutical intervention made available to patients in the last twenty five years. …

Transgenerational Effects Of Chronic Preconception Stress On Developmental And Health Outcomes In Prairie Vole Offspring: Potential Mediation By Parental Emotionality, Mother-Father Bond, Or Parental Care Quality, W. Tang Watanasriyakul

Graduate Research Theses & Dissertations

Background: A positive rearing environment is important for the health and well-being of growing offspring. Chronic parental stress can create a toxic rearing environment, which may impair developmental and sociobehavioral outcomes of the offspring. Specifically, parental stress is linked to unstable parental emotionality, tension between mother and father, and poor parenting quality, although the inter-relatedness of these factors and the mechanisms through which they contribute to the outcomes of the offspring need further investigation. The current study investigated developmental and sociobehavioral outcomes in prairie vole offspring exposed to chronic preconception stress, with parental emotionality, strength of mother-father bond, and parental …

Delayed Testosterone Treatment In A Rodent Model Of Repeat Mild Traumatic Brain Injury Attenuates Mechanisms Of Cellular Death In The Vestibular Nucleus, Michael Volyanyuk

Master's Theses

A common complaint after repetitive mild traumatic brain injury (rmTBI) is vestibular dysfunction, which can become persistent and decrease quality of life. Delayed testosterone treatment has been shown to reduce vestibular impairment and improve neuronal survival in the vestibular nucleus following rmTBI; however, the long-term molecular pathways associated with rmTBI and testosterone treatment remain widely unexplored. We utilized a 5-hit closed-head rodent rmTBI model and administered testosterone 35 days after injury (DPI). The vestibular nuclei were removed and prepared for RT-qPCR and western blotting. Gene expression and protein levels were elevated for markers of oxidative stress (NADPH oxidase 4) and …

Factors Associated With Ventilator Weaning Success And Failure In People With Spinal Cord Injury In An Acute Inpatient Rehabilitation Setting: A Retrospective Study, Radha Korupolu, Hannah Uhlig-Reche, Emmanuel Chigozie Achilike, Colton Reeh, Claudia Pedroza, Argyrios Stampas

Faculty, Staff and Student Publications

OBJECTIVES: To evaluate baseline characteristics, describe pulmonary outcomes, and identify weaning predictors for people with acute traumatic spinal cord injury (SCI) who are dependent on mechanical ventilation at admission to acute inpatient rehabilitation (AIR).

METHODS: The retrospective study was conducted at an AIR facility in the United States. It included 91 adults with acute traumatic SCI from 2015 to 2019 who were dependent on mechanical ventilation.

RESULTS: People who successfully weaned (85%) had fewer days from time of SCI to AIR admission (22 vs. 30,

CONCLUSION: In this retrospective study, there was an increased risk of pneumonia in people with …