Neurosciences Commons^™

Synergistic Neuroprotection By A Paf Antagonist Plus A Docosanoid In Experimental Ischemic Stroke: Dose-Response And Therapeutic Window, Madigan M. Reid, Andre Obenaus, Pranab K. Mukherjee, Larissa Khoutorova, Cassia R. Roque, Nicos A. Petasis, Reinaldo B. Oria, Ludmila Belayev, Nicolas G. Bazan

School of Graduate Studies Faculty Publications

Objective: We tested the hypothesis that blocking pro-inflammatory platelet-activating factor receptor (PAFR) with LAU-0901 (LAU) plus administering a selected docosanoid, aspirin-triggered neuroprotectin D1 (AT-NPD1), which activates cell-survival pathways after middle cerebral artery occlusion (MCAo), would lead to neurological recovery. Dose-response and therapeutic window were investigated. Materials and methods: Male SD rats were subjected to 2 hours of MCAo. Behavior testing (days 1-7) and ex vivo MRI on day 7 were conducted. In dose-response, rats were treated with LAU (45 and 60 mg/kg; IP), AT-NPD1 (111, 222, 333 µg/kg; IV), LAU+AT-NPD1 (LAU at 3 hours and AT-NPD1 at 3.15 hours) or …

Exogenous Short Chain Fatty Acid Effects In App/Ps1 Mice, Diana J. Zajac, Benjamin C. Shaw, David J. Braun, Stefan J. Green, Joshua M. Morganti, Steven Estus

Sanders-Brown Center on Aging Faculty Publications

Elucidating the impact of the gut microbiome on Alzheimer’s Disease (AD) is an area of intense interest. Short chain fatty acids (SCFAs) are major microbiota metabolites that have been implicated as a mediator of gut microbiome effects in the brain. Here, we tested the effects of SCFA-treated water vs. saline-treated water on APPswe/PSEN1dE9 mice maintained under standard laboratory conditions. Mice were treated with SCFAs from five months of age until ten months of age, when they were evaluated for microbiome profile, impaired spatial memory as evaluated with the radial arm water maze, astrocyte activation as measured by Gfap expression and …

Using Noise For The Better: The Effects Of Transcranial Random Noise Stimulation On The Brain And Behavior, Onno Van Der Groen, Weronika Potok, Nicole Wenderoth, Grace Edwards, Jason B. Mattingley, Dylan Edwards

Research outputs 2022 to 2026

NEUROSCI BIOBEHAV REV X (X) XXX-XXX 2021.- Transcranial random noise stimulation (tRNS) is a non-invasive electrical brain stimulation method that is increasingly employed in studies of human brain function and behavior, in health and disease. tRNS is effective in modulating perception acutely and can improve learning. By contrast, its effectiveness for modulating higher cognitive processes is variable. Prolonged stimulation with tRNS, either as one longer application, or multiple shorter applications, may engage plasticity mechanisms that can result in long-term benefits. Here we provide an overview of the current understanding of the effects of tRNS on the brain and behavior and …

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. …

Mapping Neural Responses Onto Innate And Acquired Behavior: From Insect Olfaction To Realizing A Bio-Hybrid Chemical Recognition System, Rishabh Chandak

McKelvey School of Engineering Theses & Dissertations

In many organisms, the sense of smell, driven by the olfactory system, serves as the primary sensory modality that guides a plethora of behaviors such as foraging for food, finding mates, and evading predators. Using an array of biological sensors, the olfactory system converts volatile chemical inputs from an organism’s environment into well-patterned neural responses that inform downstream motor neurons to drive appropriate behaviors (e.g., moving towards food or away from danger). For many external cues, the elicited neural responses are often determined by the genetic makeup of the organism, which assigns an innate preference, or valence, for these different …

Assessing Rat Behavioral Response To Novelty, Neha Mathew

Honors Scholar Theses

The hippocampus is the part of the brain that is involved in memory and navigation. Neurons in the hippocampus, known as place cells, fire in specific locations within this region of the brain as the subject navigates through their environment. As these cells fire, they create a map-like representation of this environment. However if the environment is altered in any way, the place cell firing pattern is adjusted to incorporate this new information. This adjustment will inevitably cause subjects to take more time to complete their task. The goal of our testing was to assess how various manipulations, both spatial …

Linking Brain Structure To Function To Value-Based Choice, Josiah Leong

Publications and Presentations

What humans choose and how their brains make choices are central questions in psychology and neuroscience. Neuroimaging research is advancing models of functional brain activity that not only correlate with, but also predict, value-based choices in humans. Physiological research in animals suggests that monosynaptic axons structurally connect the brain circuits predictive of choice. However, similar structural connections have only recently been characterized in humans, and researchers are now starting to explore links from structural brain connections to functional brain activity to behavioral choice. In this lecture, Leong presents recent findings that link multimodal neuroimaging measurements to individual differences in value-based …

Interleukin 1 Alpha Administration Is Neuroprotective And Neuro-Restorative Following Experimental Ischemic Stroke, Kathleen E. Salmeron, Michael E. Maniskas, Danielle N. Edwards, Raymond Wong, Ivana Rajkovic, Amanda L. Trout, Abir A. Rahman, Samantha Hamilton, Justin F. Fraser, Emmanuel Pinteaux, Gregory J. Bix

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Stroke remains a leading cause of death and disability worldwide despite recent treatment breakthroughs. A primary event in stroke pathogenesis is the development of a potent and deleterious local and peripheral inflammatory response regulated by the pro-inflammatory cytokine interleukin-1 (IL-1). While the role of IL-1β (main released isoform) has been well studied in stroke, the role of the IL-1α isoform remains largely unknown. With increasing utilization of intravenous tissue plasminogen activator (t-PA) or thrombectomy to pharmacologically or mechanically remove ischemic stroke causing blood clots, respectively, there is interest in pairing successful cerebrovascular recanalization with neurotherapeutic pharmacological interventions (Fraser et …

Developing Drug Therapies: Cognitive Damage In Mice Following Brain Radiation, Rachel Yuska

The Journal of Purdue Undergraduate Research

Pediatric brain cancer patients are at a high risk for radiation-induced cognitive impairment due to white matter changes in the brain. Half of six-month radiotherapy survivors develop significant changes in white matter. Previous research has shown that a mouse model can be used to show similar cognitive and behavioral deficits in human patients. The purpose of this work is to evaluate the effectiveness of two drug therapies, Donepezil and 3,3-Diindolylmethane (DIM), that could be used to either protect the brain from radiation injury or cure the cognitive injury and behavioral deficits that result from whole-brain irradiation. This project consisted of …

Reduced Gabaergic Signaling At The Axon Initial Segment Decreases Vigilance State Transitioning, Austin John Boren

UNLV Theses, Dissertations, Professional Papers, and Capstones

Sleep is a highly regulated homeostatic process that is disrupted in an estimated 50-70 million Americans. Regulation of sleep depends upon coordinated signaling of multiple neurotransmitter systems. In particular, inhibitory gamma-aminobutyric acid (GABA) signaling is required to suppress wake-active brain regions in order to initiate and maintain sleep states. GABA type A receptors (GABAARs) are ionotropic receptors with subunit compositions uniquely enriched on subcellular domains of target cells. α2 subunit-containing GABAARs are the primary target of GABA released onto the axon initial segment (AIS), a site critical for phasing the oscillatory activity of cortical cells. α2-containing GABAARs have previously been …

Different Behavioral Experiences Produce Distinctive Parallel Changes In, And Correlate With, Frontal Cortex And Hippocampal Global Post-Translational Histone Levels., Marissa Sobolewski, Garima Singh, Jay S. Schneider, Deborah A. Cory-Slechta

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

While it is clear that behavioral experience modulates epigenetic profiles, it is less evident how the nature of that experience influences outcomes and whether epigenetic/genetic "biomarkers" could be extracted to classify different types of behavioral experience. To begin to address this question, male and female mice were subjected to either a Fixed Interval (FI) schedule of food reward, or a single episode of forced swim followed by restraint stress, or no explicit behavioral experience after which global expression levels of two activating (H3K9ac and H3K4me3) and two repressive (H3K9me2 and H3k27me3) post-translational histone modifications (PTHMs), were measured in hippocampus (HIPP) …

Tau-Directed Immunotherapy For Alzheimer’S Disease, Sulana Kay Schroeder

USF Tampa Graduate Theses and Dissertations

Alzheimer’s disease (AD) is the leading cause of dementia, accounting for 50 to 80 percent of dementia cases, and the prevalence of the disease is projected to increase significantly with time. AD is characterized by severe cognitive decline with age, ultimately requiring continued caregiving and eventually death. The pathology of AD is characterized by the presence of extracellular amyloid plaques, intracellular neurofibrillary tangles (NFT) composed of hyperphosphorylated tau protein, neuron loss, and evidence of inflammation indicated by the presence of reactive microglia and astrocytes. Frontotemporal Lobe Dementia (FTLD) is a rare form of dementia that is related to AD, most …

Adolescent Cannabinoid Exposure Induces A Persistent Sub-Cortical Hyper-Dopaminergic State And Associated Molecular Adaptations In The Prefrontal Cortex., Justine Renard, Laura G Rosen, Michael Loureiro, Cleusa De Oliveira, Susanne Schmid, Walter J Rushlow, Steven R Laviolette

Brain and Mind Institute Researchers' Publications

Considerable evidence suggests that adolescent exposure to delta-9-tetrahydrocanabinol (THC), the psychoactive component in marijuana, increases the risk of developing schizophrenia-related symptoms in early adulthood. In the present study, we used a combination of behavioral and molecular analyses with in vivo neuronal electrophysiology to compare the long-term effects of adolescent versus adulthood THC exposure in rats. We report that adolescent, but not adult, THC exposure induces long-term neuropsychiatric-like phenotypes similar to those observed in clinical populations. Thus, adolescent THC exposure induced behavioral abnormalities resembling positive and negative schizophrenia-related endophenotypes and a state of neuronal hyperactivity in the mesocorticolimbic dopamine (DA) pathway. …

Analysis Of The Secondary Neurodegenerative Consequences Of Primary Oligodendrocyte Stress Through The Use Of The Novel Obiden Mouse Model, Daniel Zdzislaw Radecki

Wayne State University Dissertations

The work of this project was to develop, test and characterize a potential novel mouse model of the neurodegenerative disease Multiple Sclerosis (MS). Historically, MS has been identified as a primary autoimmune disease of the central nervous system (CNS). However, treatments based on this view have met with limited success, and in most cases, fail to prevent progression of MS from mild to moderate and severe forms. Original observations regarding axonal and neuronal pathology in the white and gray matter of the CNS were rediscovered in the 1990s. These observations indicated that even in the absence of the immune system, …

In Synch But Not In Step: Circadian Clock Circuits Regulating Plasticity In Daily Rhythms, Jennifer A. Evans, M. R. Gorman

Biomedical Sciences Faculty Research and Publications

The suprachiasmatic nucleus (SCN) is a network of neural oscillators that program daily rhythms in mammalian behavior and physiology. Over the last decade much has been learned about how SCN clock neurons coordinate together in time and space to form a cohesive population. Despite this insight, much remains unknown about how SCN neurons communicate with one another to produce emergent properties of the network. Here we review the current understanding of communication among SCN clock cells and highlight a collection of formal assays where changes in SCN interactions provide for plasticity in the waveform of circadian rhythms in behavior. Future …

Behavioral Outputs Of Fragile-X Autistic Mice Exposed To Open-Field, Randomized, Short-Term Visual Stimuli, Nicholas M. Dicola, Alexander A. Chubykin

The Summer Undergraduate Research Fellowship (SURF) Symposium

Animal models of different neurological disorders are required for studying the pathophysiology of these diseases, and for potential development of pharmacological and behavioral treatments. The scientific community often uses mouse models for behavior studies due to their powerful genetic tools and low cost. However, subjective measurement techniques are often used when analyzing mice for behavioral traits which often results in discrepancies in results. An automated tracking software would aim to eliminate these discrepancies and subjective analysis. This lab has developed a software program which offered an ability to automatically collect open-field behavioral data with simultaneous on-line analysis. Python, an open …

Behavioral Assessment Of Acute Inhibition Of System XC - In Rats, Victoria Lutgen, Jon M. Resch, Krista Qualmann, Nicholas J. Raddatz, Cristina Panhans, Ellen M. Olander, Linghai Kong, Sujean Choi, John R. Mantsch, David A. Baker

Biomedical Sciences Faculty Research and Publications

Rationale

Gaps in our understanding of glutamatergic signaling may be key obstacles in accurately modeling complex CNS diseases. System x_c ^- is an example of a poorly understood component of glutamate homeostasis that has the potential to contribute to CNS diseases.

Objectives

This study aims to determine whether system x_c ^- contributes to behaviors used to model features of CNS disease states.

Methods

In situ hybridization was used to map mRNA expression of xCT throughout the brain. Microdialysis in the prefrontal cortex was used to sample extracellular glutamate levels; HPLC was used to measure extracellular glutamate and tissue …

Inattention And Hyperactivity Among Preschool Age Children Born Prematurely, Andrew Heitzer

Wayne State University Theses

A large body of literature shows that compared to children born at term, preterm- children are at increased risk for difficulties with inattention and hyperactivity. Less consistency exists, however, in the limited body of research exploring the contribution of early biological risk to behavioral disinhibition within the population of children born prematurely. Therefore, our goal was to examine perinatal variables that may influence activity level and hyperactivity among preterm preschoolers. Ninety-eight preterm (23.4 - 33.9 weeks gestation) preschoolers (3-4 years) participated in the study. Direct measures of inattention and hyperactivity as well as parental ratings were used to evaluate behavior. …

Skill Learning Strengthens Cortical Representations Of Motor Sequences., Tobias Wiestler, Jörn Diedrichsen

Brain and Mind Institute Researchers' Publications

Motor-skill learning can be accompanied by both increases and decreases in brain activity. Increases may indicate neural recruitment, while decreases may imply that a region became unimportant or developed a more efficient representation of the skill. These overlapping mechanisms make interpreting learning-related changes of spatially averaged activity difficult. Here we show that motor-skill acquisition is associated with the emergence of highly distinguishable activity patterns for trained movement sequences, in the absence of average activity increases. During functional magnetic resonance imaging, participants produced either four trained or four untrained finger sequences. Using multivariate pattern analysis, both untrained and trained sequences could …

Striatal Dopamine Dynamics Upon Manganese Accumulation, Madiha Khalid

Wayne State University Dissertations

STRIATAL DOPAMINE DYNAMICS UPON MANGANESE ACCUMULATION

by MADIHA KHALID

August 2013

Advisor: Dr. Tiffany Mathews

Major: Chemistry (Analytical)

Degree: Doctor of Philosophy

Although manganese (Mn) is fundamental for many biological processes, exposure to excess amounts leads to a neurological disorder termed manganism. Due to its symptomatic similarity to Parkinson's disease, as well its preferential accumulation in dopamine rich brain regions, alterations in the dopamine system are implicated in the onset of manganism. In my research, Mn overexposure is mimicked via subcutaneous administration of manganese chloride to C57BL/6 mice over the course of seven days using a protocol that has been …

Behavioral And Immunological Phenotypes Of Transgenic Mice Overexpressing Human Secreted Amyloid Precursor Protein Alpha: Implications For Autism, Antoinette R. Bailey

USF Tampa Graduate Theses and Dissertations

Autism is a heterogeneous neurodevelopmental disorder that is characterized by impaired social interaction and communication as well as restricted and repetitive behaviors and focused interests. In addition to the cardinal behavioral characteristics observed for diagnosis, autistic individuals exhibit a number of comorbid conditions as well as a variety of aberrant immunological features. Recent studies report that plasma from autistic children contained elevated levels of secreted amyloid precursor protein alpha (sAPP-á), the á-secretase cleavage product of the amyloid precursor protein (APP) which is ubiquitously expressed in the brain, spleen, thymus and other organs. Interestingly, the sAPP-á fragment functions as a neurotrophic …

Cns Neural/Glial Progenitors As Targets Of Hiv-1 And Opiates: Effects On Proliferation And Population Dynamics May Alter Behavior Outcomes., Yun Kyung Hahn

Theses and Dissertations

Human immunodeficiency virus (HIV) infected patients with a history of injection opiate abuse have higher incidences of acquired immunodeficiency syndrome (AIDS) and neurological dysfunction. The use of combined anti-retroviral therapy has significantly reduced the prevalence of mortality and progression to AIDS. Due to extended life expectancy, these patients are still at a great risk for HIV-associated neurological disorders and impairment in their later life. Neural progenitor cells (NPCs) play critical roles in brain growth and repair after injury and insult. Pediatric HIV patients whose glial populations are still developing are especially at risk for central nervous system (CNS) damage. Our …

The Levels Of Analysis Revisited., Scott A Macdougall-Shackleton

Brain and Mind Institute Researchers' Publications

The term levels of analysis has been used in several ways: to distinguish between ultimate and proximate levels, to categorize different kinds of research questions and to differentiate levels of reductionism. Because questions regarding ultimate function and proximate mechanisms are logically distinct, I suggest that distinguishing between these two levels is the best use of the term. Integrating across levels in research has potential risks, but many benefits. Consideration at one level can help generate novel hypotheses at the other, define categories of behaviour and set criteria that must be addressed. Taking an adaptationist stance thus strengthens research on proximate …

Chronic Spontaneous Activity Generated In The Somata Of Primary Nociceptors Is Associated With Pain-Related Behavior After Spinal Cord Injury, Supinder S Bedi, Qing Yang, Robyn J Crook, Junhui Du, Zizhen Wu, Harvey M Fishman, Raymond J Grill, Susan M Carlton, Edgar T Walters

Journal Articles

Mechanisms underlying chronic pain that develops after spinal cord injury (SCI) are incompletely understood. Most research on SCI pain mechanisms has focused on neuronal alterations within pain pathways at spinal and supraspinal levels associated with inflammation and glial activation. These events might also impact central processes of primary sensory neurons, triggering in nociceptors a hyperexcitable state and spontaneous activity (SA) that drive behavioral hypersensitivity and pain. SCI can sensitize peripheral fibers of nociceptors and promote peripheral SA, but whether these effects are driven by extrinsic alterations in surrounding tissue or are intrinsic to the nociceptor, and whether similar SA occurs …

The Interictal State In Epilepsy And Behavior, Daniel Tice Barkmeier

Wayne State University Dissertations

Epilepsy is one of the most common neurological diseases, affecting up to 1% of the world population. Epilepsy remains poorly understood and there are currently no medications to cure it. Patients with epilepsy have both seizures as well as another type of abnormal activity between seizures, known as interictal spikes. Interictal spikes have thus far been poorly researched, yet growing evidence supports an important role for them in epilepsy. In this project, we first show the high variability between reviewers in marking interictal spikes on intracranial EEG, and then develop and test an automated detection method to solve this problem. …

Glutamate Receptors In Perirhinal Cortex Mediate Encoding, Retrieval, And Consolidation Of Object Recognition Memory., Boyer D Winters, Timothy J Bussey

Brain and Mind Institute Researchers' Publications

Object recognition is consistently impaired in human amnesia and animal models thereof. Results from subjects with permanent brain damage have revealed the importance of the perirhinal cortex to object recognition memory. Here, we report evidence from rats for interdependent but distinct stages in object recognition memory (encoding, retrieval, and consolidation), which require glutamate receptor activity within perirhinal cortex. Transient blockade of AMPA receptor-mediated synaptic transmission within perirhinal cortex disrupted encoding for short- and long-term memory as well as retrieval and consolidation. In contrast, transient NMDA receptor blockade during encoding affected only long-term object recognition memory; NMDA receptor activity was also …

Fornix Lesions Can Facilitate Acquisition Of The Transverse Patterning Task: A Challenge For "Configural" Theories Of Hippocampal Function., T J Bussey, E Clea Warburton, J P Aggleton, J L Muir

Brain and Mind Institute Researchers' Publications

Configural theories of hippocampal function predict that hippocampal dysfunction should impair acquisition of the transverse patterning task, which involves the concurrent solution of three discrimination problems: A+ versus B-; B+ versus C-; and C+ versus A-. The present study tested this prediction in rats using computer-graphic stimuli presented on a touchscreen. Experiment 1 assessed the effects of fornix lesions when the three problems were introduced sequentially (phase 1: A+ vs B-; phase 2: A+ vs B-, B+ vs C-; phase 3: A+ vs B-, B+ vs C-, C+ vs A-). Fornix lesions significantly facilitated acquisition of the complete transverse patterning …