Neuroscience and Neurobiology Commons^™

AΒ40 Reduces P-Glycoprotein At The Blood-Brain Barrier Through The Ubiquitin-Proteasome Pathway, Anika M. S. Hartz, Yu Zhong, Andrea Wolf, Harry Levine Iii, David S. Miller, Björn Bauer

Sanders-Brown Center on Aging Faculty Publications

Failure to clear amyloid-β (Aβ) from the brain is in part responsible for Aβ brain accumulation in Alzheimer's disease (AD). A critical protein for clearing Aβ across the blood–brain barrier is the efflux transporter P-glycoprotein (P-gp) in the luminal plasma membrane of the brain capillary endothelium. P-gp is reduced at the blood–brain barrier in AD, which has been shown to be associated with Aβ brain accumulation. However, the mechanism responsible for P-gp reduction in AD is not well understood. Here we focused on identifying critical mechanistic steps involved in reducing P-gp in AD. We …

Neuroprediction And Criminal Law, Fritz Allhoff

Spring Convocation

No abstract provided.

Marital Satisfaction, Error-Observation, And The Brain: Harmful Or Beneficial Effects Of Spouse Observation?, Chelsea Romney, Michael Larson

Journal of Undergraduate Research

Romney, Chelsea Marital Satisfaction, Error-observation, and the Brain: Harmful or Beneficial Effects of Spouse Observation? Faculty Mentor: Larson, Michael, Department of Psychology and Neuroscience Introduction Rewarding marital relationships are associated with many positive outcomes in one’s physical and mental health (Robles, & Kiecolt-Glaser, 2003). These benefits include improved cardiovascular functioning (Kiecolt-Glaser, & Newton, 2001), decreased depression risk (Robins & Reiger, 1991), higher self-reported levels of happiness (Proulx & Snyder-Rivas, 2013), and overall lower rates of mortality (Manzoli, Villari, Pirone & Boccia, 2007). Furthermore, positive health outcomes are not only due to marital status, but also to the quality of one’s …

Receiving Reward’S Effect On Ego-Depletion, Travis Johnson, Michael J. Larson, Phd

Journal of Undergraduate Research

Recent research suggests that willpower–the capacity to exert self-control–is a limited resource that is depleted after exertion (Job, Dweck & Walton, 2010). We aimed to explore the influence of ego-depletion on how we process rewards and punishment. Ego depletion specifically refers to the idea that self-control or willpower draws upon a limited pool of mental resources that can be used up (i.e., depleted) after cognitive exertion. For example, an experiment performed by Kathleen Vohs and Todd Heatherton (2000) demonstrated how ego depletion was relevant in how it affected chronic dieters compared to non-dieters. Their results showed that dieters, in responding …

Blockade Of Astrocytic Calcineurin/Nfat Signaling Helps To Normalize Hippocampal Synaptic Function And Plasticity In A Rat Model Of Traumatic Brain Injury, Jennifer L. Furman, Pradoldej Sompol, Susan D. Kraner, Melanie M. Pleiss, Esther J. Putman, Jacob Dunkerson, Hafiz Mohmmad Abdul, Kelly N. Roberts, Stephen William Scheff, Christopher M. Norris

Pharmacology and Nutritional Sciences Faculty Publications

Increasing evidence suggests that the calcineurin (CN)-dependent transcription factor NFAT (Nuclear Factor of Activated T cells) mediates deleterious effects of astrocytes in progressive neurodegenerative conditions. However, the impact of astrocytic CN/NFAT signaling on neural function/recovery after acute injury has not been investigated extensively. Using a controlled cortical impact (CCI) procedure in rats, we show that traumatic brain injury is associated with an increase in the activities of NFATs 1 and 4 in the hippocampus at 7 d after injury. NFAT4, but not NFAT1, exhibited extensive labeling in astrocytes and was found throughout the axon/dendrite layers of CA1 and the dentate …

Electrophysiological Testing Of Iterhemispheric Transfer In Individuals With Mild Traumatic Brain Injury, Nathan Alder, Michael J. Larson, Phd

Journal of Undergraduate Research

A key issue in mild traumatic brain injury (TBI; also known as concussion) research is the identification and validation of a cost-effective, physiological measure that accurately identifies individuals who have experienced a mild TBI, is robust against motivation difficulties, and aids in the prediction of which individuals will experience persisting cognitive or emotional side effects. Nearly two million cases of TBI occur each year (Langlois, Rutland-Brown, & Thomas, 2004). Mild TBI is considered a major health concern (Ragnarsson, 2002) and can be associated with some long-term functional deficits including memory decline and decreased job satisfaction (Carroll et al., 2004; Iverson, …

Cognitive Control And Obsessive-Compulsive Disorder, Katherine Slinn, Michael Larson

Journal of Undergraduate Research

This project was an in-depth statistical analysis of previously collected data in order to explore the hypothesis that obsessive-compulsive disorder (OCD) is associated with a decrease in the ability to regulate behavior and to apply top-down cognitive control. OCD has been diagnosed in approximately 2.2 million Americans, typically appearing in early adulthood. Approximately half of these cases show severe functional impairment (Kessler, Chiu, Demler, & Walters, 2005). Obsessions are defined as unwanted and recurrent thoughts or impulses, and compulsions are repetitive behaviors that are driven by these obsessions, such as ordering or counting (American Psychiatric Association, 2013). 20% to 30% …

Electrophysiological Testing Of Iterhemispheric Transfer In Individuals With Mild Traumatic Brain Injury, Nathan Alder, Michael J. Larson

Journal of Undergraduate Research

A key issue in mild traumatic brain injury (TBI; also known as concussion) research is the identification and validation of a cost-effective, physiological measure that accurately identifies individuals who have experienced a mild TBI, is robust against motivation difficulties, and aids in the prediction of which individuals will experience persisting cognitive or emotional side effects. Nearly two million cases of TBI occur each year (Langlois, Rutland-Brown, & Thomas, 2004). Mild TBI is considered a major health concern (Ragnarsson, 2002) and can be associated with some long-term functional deficits including memory decline and decreased job satisfaction (Carroll et al., 2004; Iverson, …

Cognitive Control And Obsessive-Compulsive Disorder, Katherine Slinn, Michael Larson

Journal of Undergraduate Research

This project was an in-depth statistical analysis of previously collected data in order to explore the hypothesis that obsessive-compulsive disorder (OCD) is associated with a decrease in the ability to regulate behavior and to apply top-down cognitive control. OCD has been diagnosed in approximately 2.2 million Americans, typically appearing in early adulthood. Approximately half of these cases show severe functional impairment (Kessler, Chiu, Demler, & Walters, 2005). Obsessions are defined as unwanted and recurrent thoughts or impulses, and compulsions are repetitive behaviors that are driven by these obsessions, such as ordering or counting (American Psychiatric Association, 2013). 20% to 30% …

Marital Satisfaction, Error-Observation, And The Brain: Harmful Or Beneficial Effects Of Spouse Observation?, Chelsea Romney, Michael Larson

Journal of Undergraduate Research

Romney, Chelsea Marital Satisfaction, Error-observation, and the Brain: Harmful or Beneficial Effects of Spouse Observation? Faculty Mentor: Larson, Michael, Department of Psychology and Neuroscience Introduction Rewarding marital relationships are associated with many positive outcomes in one’s physical and mental health (Robles, & Kiecolt-Glaser, 2003). These benefits include improved cardiovascular functioning (Kiecolt-Glaser, & Newton, 2001), decreased depression risk (Robins & Reiger, 1991), higher self-reported levels of happiness (Proulx & Snyder-Rivas, 2013), and overall lower rates of mortality (Manzoli, Villari, Pirone & Boccia, 2007). Furthermore, positive health outcomes are not only due to marital status, but also to the quality of one’s …

Effects Of Exercise On Food-Related Cognition, Tyshae Davis, Michael J. Larson

Journal of Undergraduate Research

Since the Yerkes-Dodson theory was initially put forward (as early as 1906), multiple theorists have suggested an inverted-U relationship between physiological arousal and cognitive performance. Literature on this topic, however, is mixed, with some studies showing evidence supporting the inverted-U relationship and others showing a more linear relationship. Exercise and food-related cognition is one area where the inverted-U hypothesis could be applied. Some studies have shown that high-intensity exercise induces an acute, but temporary suppression to hunger and energy intake compared to low-intensity exercise (King, Tremblay, & Blundell, 1997) and that high-intensity exercise favors negative energy balance to a greater …

Polymorphisms Of The Glucocorticoid Receptor Gene And The Association With Stress, Randall Beck, Michael J. Larson

Journal of Undergraduate Research

Polymorphisms in the GR gene are an interesting and important area of research as these polymorphisms may be associated with an attenuated ability to cope with stress. This project bridged an unexplored gap between cellular and environmental stress and the expression of the GR gene—specifically the Bcl1 polymorphism of the GR gene. Cellular stress is any damage caused to the cell that alters its ability to function properly (Milisav, 2011). The Bcl1 polymorphism has what are known as C and G alleles that are genotyped as either homozygous GG, homozygous CC, or heterozygous CG (Srivastava et al., 2011). The homozygous …

Reconstructing Representations Of Dynamic Visual Objects In Early Visual Cortex, Edmund Chong, Ariana M. Familiar, Won Mok Shim

Dartmouth Scholarship

As raw sensory data are partial, our visual system extensively fills in missing details, creating enriched percepts based on incomplete bottom-up information. Despite evidence for internally generated representations at early stages of cortical processing, it is not known whether these representations include missing information of dynamically transforming objects. Long-range apparent motion (AM) provides a unique test case because objects in AM can undergo changes both in position and in features. Using fMRI and encoding methods, we found that the “intermediate” orientation of an apparently rotating grating, never presented in the retinal input but interpolated during AM, is reconstructed in population-level, …

The Effects Of Chronic Ethanol In Δ Knockout Mice, Zachary Gardner, Scott Steffensen

Journal of Undergraduate Research

Substance abuse is a prolific problem with serious consequences. Specifically, alcohol abuse is the third leading cause of preventable mortality in the world (Mokdad et al., 2004). Each year the far-reaching effects of alcohol abuse cost the United States several hundred billion dollars annually (Office of National Policy, 2004). Treatment for individuals who suffer from this crippling disease is limited. In order to develop effective treatments we need to know more about the mechanisms of addiction and the changes that occur in the brain as a person becomes addicted.

The Effects Of Chronic Ethanol In Δ Knockout Mice, Zachary Gardner, Scott Steffensen

Journal of Undergraduate Research

Substance abuse is a prolific problem with serious consequences. Specifically, alcohol abuse is the third leading cause of preventable mortality in the world (Mokdad et al., 2004). Each year the far-reaching effects of alcohol abuse cost the United States several hundred billion dollars annually (Office of National Policy, 2004). Treatment for individuals who suffer from this crippling disease is limited. In order to develop effective treatments we need to know more about the mechanisms of addiction and the changes that occur in the brain as a person becomes addicted.

Polymorphisms Of The Glucocorticoid Receptor Gene And The Association With Stress, Randall Beck, Michael J. Larson

Journal of Undergraduate Research

Polymorphisms in the GR gene are an interesting and important area of research as these polymorphisms may be associated with an attenuated ability to cope with stress. This project bridged an unexplored gap between cellular and environmental stress and the expression of the GR gene—specifically the Bcl1 polymorphism of the GR gene. Cellular stress is any damage caused to the cell that alters its ability to function properly (Milisav, 2011). The Bcl1 polymorphism has what are known as C and G alleles that are genotyped as either homozygous GG, homozygous CC, or heterozygous CG (Srivastava et al., 2011). The homozygous …

Chronic Consumption Of A Western Diet Induces Robust Glial Activation In Aging Mice And In A Mouse Model Of Alzheimer’S Disease, Leah C. Graham, Jeffrey M. Harder, Ileana Soto Reyes, Wilhelmine N. De Vries, Simon W. M. John, Gareth R. Howell

College of Science & Mathematics Departmental Research

Studies have assessed individual components of a western diet, but no study has assessed the long-term, cumulative effects of a western diet on aging and Alzheimer’s disease (AD). Therefore, we have formulated the first western-style diet that mimics the fat, carbohydrate, protein, vitamin and mineral levels of western diets. This diet was fed to aging C57BL/6J (B6) mice to identify phenotypes that may increase susceptibility to AD, and to APP/PS1 mice, a mouse model of AD, to determine the effects of the diet in AD. Astrocytosis and microglia/monocyte activation were dramatically increased in response to diet and was further increased …

Hpcnmf: A High-Performance Toolbox For Non-Negative Matrix Factorization, Karthik Devarajan, Guoli Wang

COBRA Preprint Series

Non-negative matrix factorization (NMF) is a widely used machine learning algorithm for dimension reduction of large-scale data. It has found successful applications in a variety of fields such as computational biology, neuroscience, natural language processing, information retrieval, image processing and speech recognition. In bioinformatics, for example, it has been used to extract patterns and profiles from genomic and text-mining data as well as in protein sequence and structure analysis. While the scientific performance of NMF is very promising in dealing with high dimensional data sets and complex data structures, its computational cost is high and sometimes could be critical for …

The Impact Of Affect On Neural Mechanisms Underlying Orientation Perception, Michelle L. Fowler

Dissertations, Theses, and Capstone Projects

The underlying mechanisms used to process 2D visual information to form a unified 3D percept of the world remain largely unknown. Previous work in our lab has shown that accurate 3D perception of textured surfaces depends on the presence of specific patterns of orientation flows in the retinal image. Recent research has shown that affective state may influence the visual perception of oriented patterns. Relative to neutral face stimuli, fearful face stimuli have been shown to increase sensitivity to orientation of low spatial frequency patterns and decrease sensitivity to orientation of high spatial frequency patterns. How affective state influences the …

Neurodevelopmental Defects Associated With Gestational Exposure To Low Levels Of Dbp In Mice, Françoise Sidime

Dissertations, Theses, and Capstone Projects

The etiology of autism is thought to involve the complex interplay among genetic and environmental factors. Patterns of inheritance suggest an epigenetic component to the development of autism. A variety of environmental risk factors are known to induce epigenetic changes in DNA, affecting many genes including those autism-associated genes (AAG). The plasticizer dibutyl phthalate (DBP; CAS 84-74-2) is a developmental and reproductive toxin that causes a broad range of birth defects resulting in neurological impairments.

To date, although the effect of DBP as an endocrine and a reproductive disruptor are established, there are only few studies that address the effects …

Messenger Rna Transport And Translation Regulated By The 3' Utrs Of Dendritic Mrnas And Abnormal Alternative Splicing Of Neuroligin1 In The Fmr1 Ko Mouse Hippocampus, Tianhui Zhu

Dissertations, Theses, and Capstone Projects

Fragile X Syndrome (FXS) is one of the most commonly inherited mental retardations. It is caused by the loss of functional fragile X mental retardation protein (FMRP). Loss of functional FMRP is the most widespread single-gene cause of autism. The most prominent phenotype of FXS patients is an IQ ranging from 20 to 70. FMRP is an RNA binding protein, widely expressed in almost all tissues and highly expressed in brain. As a RNA binding protein, 85-90 % of FMRP in the brain is associated with polyribosomes. Approximately 4 % of total mRNA is associated with FMRP, which functions in …

Early Rescue Of Interneuron Disease Trajectory In Developmental Epilepsies, Ms Siehr, Jl Noebels

Faculty, Staff and Students Publications

The discovery of over 150 monogenic epilepsies and advances in early genetic diagnoses have launched a search for molecular strategies and developmental timetables to reverse or even prevent the course of these debilitating brain disorders. Orthologous rodent models of key disease genes are providing important examples of the range of targets, and serve as valuable test systems for perinatal therapeutic approaches. While gene-specific analyses of single rare 'orphan' diseases are each narrow in scope, they illuminate downstream pathways converging onto interneurons, and treatments that strengthen inhibition during cortical maturation may provide broad protection against these seemingly disparate gene errors. Several …

Efficacy Of Psychosocial Interventions In Inducing And Maintaining Alcohol Abstinence In Patients With Chronic Liver Disease: A Systematic Review, A Khan, A Tansel, Dl White, Wt Kayani, Wt Bano, J Lindsay, Hb El-Serag, F Kanwal

Faculty, Staff and Students Publications

BACKGROUND & AIMS: We conducted a systematic review of efficacy of psychosocial interventions in inducing or maintaining alcohol abstinence in patients with chronic liver disease (CLD) and alcohol use disorder (AUD). METHODS: We performed structured keyword searches in PubMed, PsychINFO, and MEDLINE for original research articles that were published from January 1983 through November 2014 that evaluated the use of psychosocial interventions to induce or maintain alcohol abstinence in patients with CLD and AUD. RESULTS: We identified 13 eligible studies that comprised 1945 patients; 5 were randomized controlled trials (RCTs). Delivered therapies included motivational enhancement therapy, cognitive behavioral therapy (CBT), …

Glial Contributions To Neural Function And Disease, Mn Rasband

Faculty, Staff and Students Publications

The nervous system consists of neurons and glial cells. Neurons generate and propagate electrical and chemical signals, whereas glia function mainly to modulate neuron function and signaling. Just as there are many different kinds of neurons with different roles, there are also many types of glia that perform diverse functions. For example, glia make myelin; modulate synapse formation, function, and elimination; regulate blood flow and metabolism; and maintain ionic and water homeostasis to name only a few. Although proteomic approaches have been used extensively to understand neurons, the same cannot be said for glia. Importantly, like neurons, glial cells have …

Eosinophilic Esophagitis In Children And Its Relationship With Parental Allergies: Texas Children's Hospital Experience, G Hiremath, D Byramji, A Pacheco, G Constantine, C Davis, R Shulman, A Olive

Faculty, Staff and Students Publications

BACKGROUND: Eosinophilic esophagitis (EoE) is an allergen-mediated, clinicopathological condition affecting all ages. The characteristics of children with EoE in the southwestern USA have not been fully described. Furthermore, very little is known about the relationship between parental allergies and risk of EoE in their offspring in this patient population. AIMS: To characterize children with EoE and to examine the relationship between prevalence of parental allergies and occurrence of EoE in their offspring at a single referral pediatric center in the southwestern USA. METHODS: Demographic and clinical information of 126 children (=18 years of age) with EoE was abstracted in a …

Binomial Regression With A Misclassified Covariate And Outcome, Sheng Luo, Wenyaw Chan, Michelle A Detry, Paul J Massman, R S. Doody

Faculty, Staff and Students Publications

Misclassification occurring in either outcome variables or categorical covariates or both is a common issue in medical science. It leads to biased results and distorted disease-exposure relationships. Moreover, it is often of clinical interest to obtain the estimates of sensitivity and specificity of some diagnostic methods even when neither gold standard nor prior knowledge about the parameters exists. We present a novel Bayesian approach in binomial regression when both the outcome variable and one binary covariate are subject to misclassification. Extensive simulation results under various scenarios and a real clinical example are given to illustrate the proposed approach. This approach …

Status Signaling And The Characterization Of A Chirp-Like Signal In The Weakly Electric Fish Steatogenys Elegans, Caitlin E. Field

Dissertations, Theses, and Capstone Projects

Sensory systems are critical to both exploratory and communicatory processes, the study of which is critical to our understanding of how animals perceive and respond to their environments. In weakly electric fishes the electrosensory system is utilized for both of these purposes. One type of communication, status signaling, is widespread across taxa and frequently hormonally modulated. This hormonal modulation keeps the signal honest, wherein the status of the sender and the production of the status signal itself are both hormone dependent. We investigated exploratory and communicatory strategies of the electromotor system in pulse-type gymnotiforms, with a focus on status communication …

Utilization Of The Clinical Laboratory For The Implementation Of Concussion Biomarkers In Collegiate Football And The Necessity Of Personalized And Predictive Athlete Specific Reference Intervals, Stefanie Podlog (Nee Schulte), Natalie N. Rasmussen, Joseph W. Mcbeth, Patrick Q. Richards, Eric Yochem, David J. Petron, Frederick G. Strathmann

Athletic Training Collection

Background: A continued interest in concussion biomarkers makes the eventual implementation of identified biomarkers into routine concussion assessment an eventual reality. We sought to develop and test an interdisciplinary approach that could be used to integrate blood-based biomarkers into the established concussion management program for a collegiate football team.

Methods: We used a CLIA-certified laboratory for all testing and chose biomarkers where clinically validated testing was available as would be required for results used in clinical decision making. We summarized the existing methods and results for concussion assessment across an entire season to identify and demonstrate the challenges with the …

The Ubiquitin-Proteasome System: Potential Therapeutic Targets For Alzheimer’S Disease And Spinal Cord Injury, Bing Gong, Miroslav Radulovic, Maria E. Figueiredo-Pereira, Christopher Cardozo

Publications and Research

The ubiquitin-proteasome system (UPS) is a crucial protein degradation system in eukaryotes. Herein, we will review advances in the understanding of the role of several proteins of the UPS in Alzheimer’s disease (AD) and functional recovery after spinal cord injury (SCI). The UPS consists of many factors that include E3 ubiquitin ligases, ubiquitin hydrolases, ubiquitin and ubiquitin-like molecules, and the proteasome itself. An extensive body of work links UPS dysfunction with AD pathogenesis and progression. More recently, the UPS has been shown to have vital roles in recovery of function after SCI. The ubiquitin hydrolase (Uch-L1) has been proposed to …

Depression, Suicide, And Performance Monitoring: Identifying Neuroelectric Markers Of Suicidal Behavior, Kaylie Carbine, Michael Larson

Journal of Undergraduate Research

From 2000-2009, suicide mortality rates increased by 15% (Rockett, et al., 2012) and 98% of individuals who complete suicide have diagnosable psychopathology (Bertolote, Fleischmann, De Leo, & Wasserman, 2003). Individuals at risk for suicide exhibit cognitive impairments in decision-making and problem-solving abilities (Pollock & Williams, 2004; Jollant, et al., 2005). These cognitive deficits may be related to deficits in performance monitoring. Performance monitoring is the ability to continually assess behavior in order to make adjustments and improve performance. Performance monitoring is mediated by the anterior cingulate cortex (ACC), which is related to cognitive control abilities. Furthermore, suicidal thoughts and behaviors …