Neuroscience and Neurobiology Commons^™

Characterization And Targeting Of Voltage-Gated Ion Channels In Meningioma Cell Lines, Erik White

Master's Theses

Meningiomas (MN) are primary brain tumors originating in the meningeal covering of the central nervous system. These tissues can evolve through familial inheritance (NF2, Cowden Syndrome, or Werner Syndrome) or sporadic mutations. The WHO categorizes MNs into three grades (I-III); Grade I contain benign tumors and Grade III the most aggressive. Increasing grade coincides with an increase in genetic diversity, making universal treatments difficult. MNs are typically treated with hydroxyurea (HU), but this chemotherapy agent has many adverse side effects, leading to research in less toxic options. This study uses ion channel antagonists for T- and L-type calcium channels using …

Characterizing A Putative Membrane Androgen Receptor In Glioma Cell Models, Emma Yuen

Master's Theses

The goal of this current research was to explore the role of a putative membraneandrogen receptor (AR) in modulating the viability of various models of glioma/astrocytoma, relative to normal (non-tumor) astrocytes. We hypothesized that binding to the membrane AR could enhance the sensitivity of glioma cells to toxic insult (i.e., the chemotherapeutic, Temozolomide, TMZ), while leaving “normal” astrocytes unscathed. Our data reveal that binding to the putative membrane AR sensitized C6 glioma cells to TMZ and the oxidative/metabolic insult, iodoacetic acid (IAA). And while there was some evidence that binding to the membrane AR could enhance the effect of TMZ …

The Effect Of Gonadal Steroids Following Repeat Mild Traumatic Brain Injury On Anxiety-Like Behaviors In Rats, Trevor Nykamp

Master's Theses

Traumatic brain injury (TBI) affects millions of people in the U.S. each year. This thesis worked to address anxiety, a common emotional symptom following TBI, by utilizing a five-hit repeat mild TBI (rmTBI) experimental model. First, changes in gonadal status following injury and the severity of anxiety symptoms experienced were investigated. Our data revealed that suppressed testosterone levels following rmTBI resulted in significantly more anxiety-like behaviors across several observational variables. Even more, some of these behaviors were reduced by providing testosterone supplementation immediately following injury.Another goal of this work was to investigate the role of mitochondrial dysfunction, measured by COX4i1 …

Gephyrin-Lacking Pv Synapses On Neocortical Pyramidal Neurons, Dika A. Kuljis, Kristina D. Micheva, Ajit Ray, Waja Wegner, Ryan Bowman, Daniel V. Madison, Katrin I. Willig, Alison L. Barth

Biology Faculty Publications

Gephyrin has long been thought of as a master regulator for inhibitory synapses, acting as a scaffold to organize γ-aminobutyric acid type A receptors (GABA_ARs) at the post-synaptic density. Accordingly, gephyrin immunostaining has been used as an indicator of inhibitory synapses; despite this, the pan-synaptic localization of gephyrin to specific classes of inhibitory synapses has not been demonstrated. Genetically encoded fibronectin intrabodies generated with mRNA display (FingRs) against gephyrin (Gephyrin.FingR) reliably label endogenous gephyrin, and can be tagged with fluorophores for comprehensive synaptic quantitation and monitoring. Here we investigated input- and target-specific localization of gephyrin at a defined …

Influence Of 2,5-Dimethoxy-4-Iodoamphetamine (Doi) On Ethanol Preference And Consumption In C57bl/6 Male Mice, Alaina M. Jaster, Sam Gottlieb, Michael Miles, Javier González-Maeso

Graduate Research Posters

Substance use disorders (SUD) account for a large number of mental health diagnosis in the United States and around the world. Approximately 13.6 million adults 26 or older and 5.1 million young adults (ages 18-24) battled with a SUD in 2017. Alcohol Use Disorder (AUD) alone effects nearly 6% of the adult population within the United States. This creates a substantial burden on the individual, with alcohol being the third-leading cause of preventable death in the United States. Few treatments for AUD exist, with no new FDA-approved therapeutic treatments within the last 15 years. Additionally, the limited treatments we do …

Stratifying Ischaemic Stroke Patients Across 3 Treatment Windows Using T2 Relaxation Times, Ordinal Regression And Cumulative Probabilities, Bryony Mcgarry, Elizabeth Hunter, Robin Damian, Michael Knight, Philip Clatworthy, George Harston, Keith Muir, Risto Kauppinen, John Kelleher

Conference papers

Unknown onset time is a common contraindication for anti-thrombolytic treatment of ischaemic stroke. T2 relaxation-based signal changes within the lesion can identify patients within or beyond the 4.5-hour intravenous thrombolysis treatment-window. However, now that intra-arterial thrombolysis is recommended between 4.5 and 6 hours from symptom onset and mechanical thrombectomy is considered safe between 6 and 24 hours, there are three treatment-windows to consider. Here we show a cumulative ordinal regression model, incorporating the T2 relaxation time, predicts the probabilities of a patient being within one of the three treatment-windows and is more accurate than signal intensity changes from T2 weighted …

Glial Granules And Germline Proteins In The Drosophila Brain, Samuel J. Tindell

Murray State Theses and Dissertations

My overarching goal was to elucidate the role of Tudor (Tud) protein in the Drosophila brain. Tud is an evolutionarily conserved molecular scaffold, containing 11 Tud domains which bind to symmetrically dimethylated arginine (sDMA) residues in a variety of proteins. Tud is an essential component of embryonic ribonucleoprotein complexes (RNPs) called germ granules that contain RNAs and proteins crucial to the differentiation and maintenance of germ cells, the specialized class of stem cells that ultimately give rise to the next generation of organism. In the absence of Tud, there is a complete abolishment of germ cells highlighting its important role …

Animal Sentience: History, Science, And Politics, Andrew N. Rowan, Joyce M. D'Silva, Ian J.H. Duncan, Nicholas Palmer

Animal Sentience

This target article has three parts. The first briefly reviews the thinking about nonhuman animals’ sentience in the Western canon: what we might know about their capacity for feeling, leading up to Bentham’s famous question “can they suffer?” The second part sketches the modern development of animal welfare science and the role that animal-sentience considerations have played therein. The third part describes the launching, by Compassion in World Farming, of efforts to incorporate animal sentience language into public policy and regulations concerning human treatment of animals.

The Role Of Leadership Communication Patterns On Organizational Effectiveness, Nidal Pascoe

Walden Dissertations and Doctoral Studies

Abstract The communication patterns of leaders in the workplace are vital to ensuring productivity and meeting organizational mission and goals. The quality of workplace communication from the leaders impacts the perceptions of employees about the workplace and their ability to fulfill organizational missions and goals. Communication can be delivered through multiple technological means, in person, and in writing. Message delivery also can convey the tone of the sender. The purpose of this case study was to identify the communication patterns between the executive leaders and six of eight site leaders of a nonprofit counseling center focused on serving children and …

Describing A Putative Corollary Discharge Circuit In Drosophila, Kaitlyn Nicole Boone

Graduate Theses, Dissertations, and Problem Reports (ETD)

Corollary discharge (CD) circuits provide critical information about movement and behavior to provide context to sensory processing. However, to date, there has not been a comprehensive study of CD circuits at a single-cell level. In this thesis, I aimed to resolve the connectivity of ascending histaminergic neurons, consisting of two pairs, the mesothoracic pair (MsAHNs) and metathoracic pair (MtAHNs) at a single-cell level and characterize contexts of activation. Using transgenic techniques, connectomics and transcriptomics, we identify neural populations receiving input from the AHNs and neural populations with significant output to the AHNs. We explored where the AHNs predominantly receive synaptic …

Expanding On The Involvement Of Primary Cilia In Neurological Function Through Observing Eeg/Emg Changes In Different Genotypic Mice, Gabriella M. Palermo

Honors Theses and Capstones

Primary cilia have been known to regulate neurological functions, as primary cilia exist on astrocytes and neurons in the mature brain. More is being discovered about primary cilia and their role in the vertebrate nervous system; however, little is known about their functions and molecular pathways in the mature brain. There also lacks methods of diagnosis for primary cilia-related defects and diseases. The purpose of this project was to provide more information on the involvement of cilia in the neurological functions and offer a potential means for diagnosis of cilia-related disorders by comparing the EEG and EMG signals of wildtype …

Multimodal Neuroscience Data Modeling And Inference, Sima Azizi

Doctoral Dissertations

“Mathematical models can be combined with deep learning and machine learning methods to provide new insights in neuroscience. The field of neuroscience is characterized by rich datasets that include fluid biomarkers, EEG signals, and advanced neuroimages. Recent advances in natural language processing have led to the opportunity to gain additional insights from rapidly growing text databases as well as electronic health records. In this research, we focus on applying computational intelligence methods to the analysis of three different complex data sources: blood levels of disease biomarkers, EEG signals from schizophrenic patients, and disease phenotypes encoded in electronic health records. First, …

A Longitudinal Investigation Of Functional Activity Changes From Vision Therapy: A Study Of Binocularly Normal Controls And Patients With Convergence Insufficiency, Cristian Morales Carrasco

Dissertations

Convergence insufficiency (CI) is a binocular vision dysfunction in which the person has difficulty maintaining a sustained fixation on an object in the near field of view. This condition is present in about 5% of the general population and with a greater prevalence in patients with traumatic brain injury or attentional deficit hyperactivity disorder. One therapeutic intervention for CI is Office-Based Vergence and Accommodative therapy (OBVAT) which is successful in about 75% of the pediatric and young adult population. The neural mechanism by which OBVAT leads to a sustained reduction in visual symptoms is not fully understood. Vergence eye movements …

A Conformation Variant Of P53 Combined With Machine Learning Identifies Alzheimer Disease In Preclinical And Prodromal Stages, Giulia Abate, Marika Vezzoli, Letizia Polito, Antonio Guaita, Diego Albani, Moira Marizzoni, Emirena Garrafa, Alessandra Marengoni, Gianluigi Forloni, Giovanni B. Frisoni, Jeffrey L. Cummings, Maurizio Memo, Daniela Uberti

School of Medicine Faculty Research

© 2020 by the authors. Li-censee MDPI, Basel, Switzerland. Early diagnosis of Alzheimer’s disease (AD) is a crucial starting point in disease man-agement. Blood-based biomarkers could represent a considerable advantage in providing AD-risk information in primary care settings. Here, we report new data for a relatively unknown blood-based biomarker that holds promise for AD diagnosis. We evaluate a p53-misfolding conformation rec-ognized by the antibody 2D3A8, also named Unfolded p53 (U-p532D3A8+), in 375 plasma samples derived from InveCe.Ab and PharmaCog/E-ADNI longitudinal studies. A machine learning approach is used to combine U-p532D3A8+ plasma levels with Mini-Mental State Examination (MMSE) and apolipoprotein E …

Neurocounseling And The Counseling Profession: Integrating Neuroscience Into The Practice Of Counseling, Sherri Clark

Dissertations, Theses, and Projects

Neurocounseling integrates Neuroscience into mental health counseling by using psychoeducation, teaching, and illustrations as well as other forms of therapy (CBT, Interpersonal Psychotherapy, Narrative Therapy, etc.) to assist clients in understanding the neurological basis of many mental and behavioral health concerns. Clients can benefit from Neurocounseling as they gain a more comprehensive understanding of the central nervous system and brain function in connection to the body, cognition, mood, and behaviors, also known as the mind and body connection. Neuroplasticity and neurogenesis allow us to understand the brain’s amazing capability to grow and change. Understanding neuroscience allows for more integrated case …

Beyond Low-Earth Orbit: Characterizing Immune And Microrna Differentials Following Simulated Deep Spaceflight Conditions In Mice, Amber M. Paul, Margareth Cheng-Campbell, Elizabeth A. Blaber, Sulekha Anand, Sharmila Bhattacharya

Publications

Spaceflight missions can cause immune system dysfunction in astronauts with little understanding of immune outcomes in deep space. This study assessed immune responses in mice following ground-based, simulated deep spaceflight conditions, compared with data from astronauts on International Space Station missions. For ground studies, we simulated microgravity using the hindlimb unloaded mouse model alone or in combination with acute simulated galactic cosmic rays or solar particle events irradiation. Immune profiling results revealed unique immune diversity following each experimental condition, suggesting each stressor results in distinct circulating immune responses, with clear consequences for deep spaceflight. Circulating plasma microRNA sequence analysis revealed …

Prenatal Alcohol Exposure Alters Transcriptional Expression Of Stress And Tlr4-Related Immune Signaling Factors In The Brain Following Early Life Stress, Chaselyn D. Ruffaner-Hanson

Biomedical Sciences ETDs

Background: Depression and anxiety disorders, believed to be caused by stress-related neuropeptides and pro-inflammatory molecules in the brain, are prevalent comorbidities of fetal alcohol spectrum disorders (FASD).

Methods: Brain tissue was collected following a 4-hour maternal separation stress during the early postnatal period, postnatal days 10 and 12, from mice subjected to 1^st and 2^nd trimester prenatal alcohol exposure (PAE).

Hypothesis: We hypothesized that PAE leads to glucocorticoid receptor insensitivity, stress molecule overexpression, and potentiated toll-like receptor 4 (TLR4) pathway inflammatory responses in the brain following early life stress.

Results: PAE and stress increased mRNA expression of TLR4 …

The Role Of Anti-Inflammatory Cytokine Interleukin-10 (Il-10) In Tauopathies, Lea L. Weston

Biomedical Sciences ETDs

Tauopathies are neurodegenerative diseases, including Alzheimer’s disease, that are associated with pathological accumulation of the microtubule associated protein tau (MAPT, or tau) (Lee et al., 2001). Abnormal hyperphosphorylated tau (pTau) strongly correlate with cognitive impairment (Nelson et al., 2012). Neuroinflammation is also associated with tauopathies (Gerhard et al., 2006b; Edison et al., 2008) and is implicated in driving tau pathology (Yoshiyama et al., 2007, Maphis et al., 2015b). Therefore, it is compelling to understand the role of anti-inflammatory cytokines in limiting neuroinflammation and tau pathology. Interleukin-10 (IL-10) is a well-established anti-inflammatory cytokine with roles in limiting inflammation in the central …

Quality Of Life Among Injectable And Oral Disease-Modifying Therapy Users In The Pacific Northwest Multiple Sclerosis Registry., Tamela Stuchiner, Lindsay Lucas, Elizabeth Baraban, Kateri Spinelli, Chiayi Chen, Alden Smith, Lobat Hashemi, Stanley Cohan

Articles, Abstracts, and Reports

BACKGROUND: Nine oral disease-modifying therapies (DMTs) have been approved for the treatment of multiple sclerosis (MS) in the United States. Few studies have examined self-reported quality of life (QoL) and functional status outcomes among patients who switch to oral medications from injectable MS therapies. This study compares self-reported QoL and disability status between participants switching from injectable to oral DMTs, to those who stay on injectable DMTs continuously for the same time period.

METHODS: Longitudinal data were assessed from relapsing MS participants in the Pacific Northwest MS Registry completing a minimum of two surveys between 2012 and 2018 with a …

Implementation Of A Guideline For Major Depressive Disorder In A Private Practice Clinic, Doreen Phillips

Doctor of Nursing Practice

Major depressive disorder (MDD) is a chief mental health illness that carries a profound economic burden. Many who suffer from MDD find little to no relief with traditional pharmacological interventions.The 2010 American Psychiatric Association Guidelines for Treatment of Patients with MDD recognized TMS as a second-line treatment choice. Several double-blind, randomized controlled trials illustrated the efficacy and safety of TMS as a viable treatment option for MDD. The purpose of this project was to implement standardized processes through the use of a treatment guideline to help provide comprehensive treatment options for patients suffering from moderate to severe major depressive disorder …