Neurosciences Commons^™

The Importance Of Protein Context In Spinocerebellar Ataxia Type 3, Sean Luis Johnson

Wayne State University Dissertations

Spinocerebellar Ataxia Type 3 (SCA3) is a member of the family of polyglutamine (polyQ) neurodegenerative disorders that includes Huntington's Disease and several other SCAs. SCA3, the most common dominant ataxia in the world, is caused by polyQ tract expansion in the protein, ataxin-3. How SCA3 occurs and how to treat it remain unresolved issues. The primary culprit of toxicity in all polyQ diseases is the glutamine repeat: its abnormal expansion leads to neuronal dysfunction and death. With that said, there is indisputable evidence that the way polyQ-dependent toxicity presents—areas impacted, cellular processes perturbed—is predicated in large part on regions outside …

Investigating The Relationship Between Biological Age And Mutant Huntingtin Misfolding, Ratnesh Kesineni

Honors Undergraduate Theses

Huntington Disease (HD) is an autosomal dominant neurodegenerative disease caused by an expansion of a CAG trinucleotide repeat tract in the huntingtin (HTT) gene. This CAG tract expansion causes production of mutant HTT (mtHTT) protein, which misfolds and forms inclusions in the brain that accumulate with age. Misfolded mtHTT aggregates have been linked with increased cell death in neuron cell culture, leading to speculation that mtHTT aggregates cause cell death. However, there are mouse lines that have robust mtHTT inclusion deposition, but no HD-like signs or neurodegeneration. Furthermore, neuronal HD cultured cells with inclusions were found to be …

Backward Walking: A Novel Marker Of Fall Risk, Cognitive Dysfunction, And Myelin Damage In Persons With Multiple Sclerosis, Erin Edwards

Wayne State University Dissertations

Multiple sclerosis (MS) is a progressive, neurologic disease of the central nervous system that causes debilitating motor, sensory and cognitive impairments. As a result, persons with MS are at an increased risk for falls and falls represent a serious public health concern for the MS population. The current clinical measures used to assess fall risk in MS patients lack sensitivity and predictive validity for falls and are limited in their ability to capture to multiple functional domains (i.e., motor, sensory, cognitive and pathological domains) that are impaired by MS. Backward walking sensitively detects falls in the elderly and other neurologic …

Dancing The Storm: Neurobiological Correlates Of Trauma-Related Psychopathology In Youth Resettled As Refugees, And The Efficacy Of Creative Arts And Movement Therapies To Address Trauma-Related Psychopathology, Lana Ruvolo Grasser

Wayne State University Dissertations

Exposure to stress and trauma activates key adaptive pathways, including the sympathetic adrenomedullary system and the immune system, which can result in long-term health impacts of trauma especially when experienced during sensitive developmental periods. Alterations in these systems are measurable through non-invasive methods including skin conductance response (SCR), fear potentiated startle (FPS), and inflammation. Research regarding the impact of trauma, and more specifically posttraumatic stress disorder, has primarily focused on adults, and there is a paucity of neurobiological research in displaced populations—like refugees—who may experience higher rates of trauma exposure and related psychopathology. The present study measured SCR to a …

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 Video Head-Impulse Test (Vhit): Variability Of Vestibulo-Ocular Reflex Gain In Individuals Without Vestibulopathy, Laurel Elise Money-Nolan, Ashley G. Flagge, Elizabeth M. Adams

V&B Lab Publications

Learning Objectives:

1. Discuss the variability in VOR gain obtained through vHIT testing in young individuals without vestibulopathy

2. Categorize the factors affecting variability in VOR gain in asymptomatic individuals

3. Explain recommendations for improving reliability and decreasing variability of VOR gain in vHIT testing

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 …

Associations Of The Lipidome With Ageing, Cognitive Decline And Exercise Behaviours, Maria Kadyrov, Luke Whiley, Belinda Brown, Kirk I. Erickson, Elaine Holmes

Research outputs 2022 to 2026

One of the most recognisable features of ageing is a decline in brain health and cognitive dysfunction, which is associated with perturbations to regular lipid homeostasis. Although ageing is the largest risk factor for several neurodegenerative diseases such as dementia, a loss in cognitive function is commonly observed in adults over the age of 65. Despite the prevalence of normal age-related cognitive decline, there is a lack of effective methods to improve the health of the ageing brain. In light of this, exercise has shown promise for positively influencing neurocognitive health and associated lipid profiles. This review summarises age-related changes …

Walking Improvement In Chronic Incomplete Spinal Cord Injury With Exoskeleton Robotic Training (Wise): A Randomized Controlled Trial, Dylan J. Edwards, Gail Forrest, Mar Cortes, Margaret M. Weightman, Cristina Sadowsky, Shuo-Hsiu Chang, Kimberly Furman, Amy Bialek, Sara Prokup, John Carlow, Leslie Vanhiel, Laura Kemp, Darrell Musick, Marc Campo, Arun Jayaraman

Research outputs 2022 to 2026

Study design:

Clinical trial.

Objective:

To demonstrate that a 12-week exoskeleton-based robotic gait training regimen can lead to a clinically meaningful improvement in independent gait speed, in community-dwelling participants with chronic incomplete spinal cord injury (iSCI).

Setting:

Outpatient rehabilitation or research institute.

Methods:

Multi-site (United States), randomized, controlled trial, comparing exoskeleton gait training (12 weeks, 36 sessions) with standard gait training or no gait training (2:2:1 randomization) in chronic iSCI ( > 1 year post injury, AIS-C, and D), with residual stepping ability. The primary outcome measure was change in robot-independent gait speed (10-meter walk test, 10MWT) post 12-week intervention. Secondary …

Transcranial Magnetic Stimulation To Assess Motor Neurophysiology After Acute Stroke In The United States: Feasibility, Lessons Learned, And Values For Future Research, Yi-Ling Kuo, David J. Lin, Isha Vora, Julie A. Dicarlo, Dylan J. Edwards, Teresa J. Kimberley

Research outputs 2022 to 2026

Transcranial magnetic stimulation (TMS) has been widely applied in both basic and clinical neuroscience since its introduction in 1985 . . .

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 …

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 …

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 …

An Aphasia Research Agenda – A Consensus Statement From The Collaboration Of Aphasia Trialists, Myzoon Ali, Efstathia Soroli, Luis M. T. Jesus, Madeline Cruice, Jytte Isaksen, Evy Visch-Brink, Kleanthes K. Grohmann, C. Jagoe, Tarja Kukkonen, Spyridoula Varlokosta, Carlos Hernandez-Sacristan, Vicente Rosell-Clari, Rebecca Palmer, Silvia Martinez-Ferreiro, Erin Godecke, Sarah J. Wallace, Ruth Mcmenamin, David Copland, Caterina Breitenstein, Audrey Bowen, Ann-Charlotte Laska, Katerina Hilari, Marian C. Brady

Research outputs 2014 to 2021

Coordination of international aphasia research would minimise duplication of effort, support synergistic international activities across languages and multidisciplinary perspectives, and promote high-quality conduct and reporting of aphasia research, thereby increasing the relevance, transparency, and implementation of findings. The Collaboration of Aphasia Trialists (CATs) sought to develop an aphasia research agenda to direct future research activities, based on priorities shared by people with aphasia, family members, and healthcare professionals. Our established international research network spanning 33 countries contributed to this activity. Research literature reporting the priorities of stakeholders was reviewed and synthesized (phase 1). Representatives from Working Groups on Aphasia Assessment …

Alzheimer's Disease Research Progress In Australia: The Alzheimer's Association International Conference Satellite Symposium In Sydney, Claire E. Sexton, Kaarin J. Anstey, Filippo Baldacci, C. J. Barnum, Anna M. Barron, Kaj Blennow, Henry Brodaty, Samantha Burnham, Fanny M. Elahi, Jürgen Götz, Yun-Hee Jeon, Maya Koronyo-Hamaoui, Susan M. Landau, Nicola T. Lautenschlager, Simon M. Laws, Darren M. Lipnicki, Hanzhang Lu, Colin L. Masters, Wendy Moyle, Akinori Nakamura, Giulio Maria Pasinetti, Naren Rao, Christopher Rowe, Perminder S. Sachdev, Peter R. Schofield, Einar M. Sigurdsson

Research outputs 2014 to 2021

The Alzheimer's Association International Conference held its sixth Satellite Symposium in Sydney, Australia in 2019, highlighting the leadership of Australian researchers in advancing the understanding of and treatment developments for Alzheimer's disease (AD) and other dementias. This leadership includes the Australian Imaging, Biomarker, and Lifestyle Flagship Study of Ageing (AIBL), which has fueled the identification and development of many biomarkers and novel therapeutics. Two multimodal lifestyle intervention studies have been launched in Australia; and Australian researchers have played leadership roles in other global studies in diverse populations. Australian researchers have also played an instrumental role in efforts to understand mechanisms …

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 …

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 …

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 …