Neuroscience and Neurobiology Commons^™

Inhibition Of Mitochondrial Fission Activates Glycogen Synthesis To Support Cell Survival In Colon Cancer, Sumati Raj Hasani, Lyndsay E. A. Young, Warren Van Nort, Moumita Banerjee, Dylan R. Rivas, Jinhwan Kim, Xiaopeng Xiong, Ramon C. Sun, Matthew S. Gentry, Hiromi Sesaki, Tianyan Gao

Markey Cancer Center Faculty Publications

Metabolic reprogramming has been recognized as one of the major mechanisms that fuel tumor initiation and progression. Our previous studies demonstrate that activation of Drp1 promotes fatty acid oxidation and downstream Wnt signaling. Here we investigate the role of Drp1 in regulating glycogen metabolism in colon cancer. Knockdown of Drp1 decreases mitochondrial respiration without increasing glycolysis. Analysis of cellular metabolites reveals that the levels of glucose-6-phosphate, a precursor for glycogenesis, are significantly elevated whereas pyruvate and other TCA cycle metabolites remain unchanged in Drp1 knockdown cells. Additionally, silencing Drp1 activates AMPK to stimulate the expression glycogen synthase 1 (GYS1) mRNA …

Proteasome Inhibition Protects Blood–Brain Barrier P-Glycoprotein And Lowers Aβ Brain Levels In An Alzheimer’S Disease Model, Milica Vulin, Yu Zhong, Bryan J. Maloney, Björn Bauer, Anika M. S. Hartz

Markey Cancer Center Faculty Publications

Background Loss of P-glycoprotein (P-gp) at the blood–brain barrier contributes to amyloid-β (Aβ) brain accumulation in Alzheimer’s disease (AD). Using transgenic human amyloid precursor protein (hAPP)-overexpressing mice (Tg2576), we previously showed that Aβ triggers P-gp loss by activating the ubiquitin–proteasome pathway, which leads to P-gp degradation. Furthermore, we showed that inhibiting the ubiquitin-activating enzyme (E1) prevents P-gp loss and lowers Aβ accumulation in the brain of hAPP mice. Based on these data, we hypothesized that repurposing the FDA-approved proteasome inhibitor, bortezomib (Velcade®; BTZ), protects blood–brain barrier P-gp from degradation in hAPP mice in vivo.

Methods We treated hAPP mice with …

Investigating Monodelphis Domestica As An Alternative To The Mus Musculus As An Animal Model, Cristian M. Botello, John L. Vandeberg, Mario Gil

Research Symposium

Background: Mus Musculus is one of the first and one of the most widely used animal models in current neuroscience literature (Phifer-Riley & Nachmann, 2015). However, the research community needs alternatives to rodent models to study the mammalian brain. Research is needed to see if antibodies that target tyrosine hydroxylase, which are well researched in mice, can also be used to study the Monodelphis domestica brain.

Methods: Following transcardial perfusions and brain extractions, mouse and opossum brains were processed and stained for tyrosine hydroxylase (and with Nissl). Opossum brains will then be sliced and processed using IHC methods to compare …

Cyclophosphamide And Epirubicin Induce Apoptotic Cell Death In Microglia Cells, Rafael De La Hoz-Camacho

Research Symposium

Background. Chemotherapy Related Cognitive Impairment’s (CRCI), diminish patient’s quality life, being breast cancer (BC) patients the most affected. Microglia is described to play a major role in CRCI; hence, the aim of this research was to describe the cytotoxicity of cyclophosphamide (CTX) and Epirubicin (EPI), on microglia (SIM-A9), compared to BC cells (4T1).

Methods. We assessed cell viability (Resazurin) and cell death (AnnV), as well as nuclear damage with γ-H2AX, p53, p16 and cell cycle analysis (PI staining) by flow cytometry (FC). Furthermore, we evaluated ΔΨm (DIOC6), ROS (DCFDA) and NO (DAF-FM) production. Finally, caspase activation (TF2-VAD-FMK) and autophagy (CYTO-ID). …

The Eyes Beyond The Screen: Digital Media Policy And Child Health, Yahia Al-Qudah

Research Symposium

Background: Modern communication technology and digital media have provided society with a foundation for instant messaging. Pictures, videos, and texts connect individuals with families, friends, and the world. Consequently, digital media has accelerated exposure to risk in which children and adolescents are most vulnerable. This project’s objective is to 1) congregate and highlight current knowledge about the impact of digital media on child health, and 2) underline deficiencies in related laws and regulations as well as offer solutions in digital media policy.

Methods: A systematic literature review was conducted through the JAMA Pediatrics database with keywords such as “digital media,” …

Gamma-Aminobutyric Acid In The Midbrain: Role In Sensation, Perception, And Neurological Disorders, Truc Le, Cristian Botello, John Vandeberg, Mario Gil

Research Symposium

Background: Altered GABA expression in the midbrain is associated with neurological conditions like epilepsy and Parkinson’s Disease. In the genetically epilepsy prone rat, an increase in GABA neurons in the inferior colliculus increases seizure susceptibility. In contrast, Parkinson’s Disease is associated with altered GABA expression in the substantia nigra. The purpose of this study is to identify patterns between the sensory and motor regions of the midbrain and to quantify a baseline of GABA neurons in these areas.

Methods: The Allen Institute’s reference atlas of the mouse and BrainMap.org was used to identify the sensory and motor areas of the …

Palmitoylation As A Regulator Of Maguk Proteins Postsynaptic Localization, Rozena Shirvani-Arani, Santiago Balderas, Yonghong Zhang, Xioaqian Fang

Research Symposium

Synaptic plasticity is the ability of the brain to make changes and the changes occur at synapses. To achieve the complicated functions, a good number of proteins are present at synapse and are called synaptic proteins. To stabilize these proteins at synapses, proteins are modified through posttranslational modifications (PTMs). The most studied PTMs include phosphorylation, acetylation, ubiquitination, glycosylation, palmitoylation, etc. Palmitoylation is a type of lipid modification and has received more attention recently for its contribution to protein trafficking, localization, and interaction in various synaptic plasticity. The membrane-associated guanylate kinase (MAGUK) family includes PSD-95, PSD-93 (also known as chapsyn-110), SAP102, …

Understanding The Resources, Barriers, Facilitators And Interests About Aging And Dementia Research Of Community Members From The Rio Grande Valley, Karla Daniela Lopez Lorenzo, Rosa V. Pirela Mavarez, Gabriela Osuna, Kendra Stine, Nathalie Chacon, Noe Garza, Gladys E. Maestre

Research Symposium

Background: One of ten people aged 65 develops Alzheimer’s Disease and it is one of the sixth-leading cause of death in the United States. The Rio Grande Valley (RGV) is mostly constituted by Hispanic/Latinos (93%), a population that has a 1.5X increased risk of AD onset. Nevertheless, there are not enough resources to support people living with dementia and their care partners. This study will leverage research efforts deployed by the RGV Alzheimer’s Disease Resource Center for Minority Aging Research to understand the social representations about the resources, barriers, facilitators, and interests of the RGV community about dementia and Alzheimer’s …

Prenatal Cafeteria Diet Exposure Promotes Lymphocyte Infiltration Into The Brain And Autism-Like Behavior In The Offspring Of C57bl6 Mice, José Alfredo Castillo Luna, Martín García Juárez, Diana Reséndez Pérez, Alberto Camacho Morales

Research Symposium

Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with an array of etiological causes, including environmental, genetic, and immunological triggers. High-energy diets activate the immune system during prenatal stages favoring infiltration of peripheral immune cells and cytokines into the brain by the choroid plexus and circumventricular regions and altering microglial activity. Accumulation of immune entities and microglia activation in brain have been reported to disrupt social behavior. However, the interplay between prenatal exposure to high-energy diets, neuroinflammation and defective social behavior has not been reported.

Methods: Female C57BL6 mice were exposed to cafeteria diet during pregnancy and lactation. The …

Differential Cortical Monoamines Release During Exercise In Rats Chronically Implanted With Microdialysis Probes, Christine G. Gerin

Research Symposium

Physical exercise is known to positively influence mood, to reduce anxiety and to improve reaction to stress. Cerebral monoaminergic systems are thought to underly the neurochemical influence of exercise on mood and behavior. We hypothesized that beneficial effects of exercise can be shown by variations of neurotransmitters release in the cerebral cortex. We aimed at demonstrating that there is a temporal relationship between release of plasma and cerebral monoamines (A, NA, 5-HT, DA) and spontaneous running exercise in rats. Ten Spague Dawley rats (250 g) were chronically implanted (for up to 39 days) with a left common carotid cannula and …

Editorial: Sex Differences In The Neurobiology Of Drug Relapse Vulnerability, Daniel F Manvich, Jessica A Loweth, Wendy J Lynch, Jayme R Mcreynolds

Rowan-Virtua School of Osteopathic Medicine Departmental Research

No abstract provided.

The Neural Sequalae Of Subjectively Experiencing Autobiographical Memories From The Remote Past And Recent Present Using Fmri, Ava G. Peruski, Nim Singh, Brendan E. Depue

The Cardinal Edge

Autobiographical memory is central to one's sense of self and continuity from past to present. Despite this, there is little research on the neural correlates underlying individual subjective experience of autobiographical memory and how that is related to brain phenomena (i.e., activity, communication). The purpose of this study was to help minimize this gap. We recruited twenty healthy adult participants, who were asked to generate memory cues (1-3 word descriptions) for locations and objects from their early and recent life. After 24 hours, participants were shown these cues then asked to recall the appropriate memory while in an fMRI scanner. …

All-Cause And Opioid-Related Mortality Compared Between Traumatic Spinal Cord Injury And The Us General Population, Jaden Whitehead, Beatrice Ugiliweneza

The Cardinal Edge

Individuals with spinal cord injury (SCI) are susceptible to the misuse of opioids due to the introduction of these substances for pain management. There are very few studies examining the relationship between unintentional deaths caused by opioid usage following spinal cord injury. The objective of this study was to evaluate the trend of opioid-related mortality of individuals with spinal cord injury (SCI) over the years and compare these findings to the mortality rates due to opioid misuse in the general population. In this study, we used data provided by the National Spinal Cord Injury Model Systems (NSCIMS) for SCI 1999-2016 …

Post-Activation Performance Enhancement Through Variable Loading Maintains Power Output Over Five Sets In Highly Trained Athletes, Robert Rocanelli, Morgan Siegel, Pedro Yunes, Pete Bommarito, Monique Mokha

Journal for Sports Neuroscience

The goal was to examine the acute effects of five sets of variable loading (VL) on the post-activation performance enhancement (PAPE) response during a live training session in highly trained athletes. PAPE is the phenomenon where acute improvements in power production in light loaded movements occur post near maximal loaded muscle contraction. PAPE may be induced with VL where resistance in the form of chains or bands is added to the bar as it displaces in the concentric phase. Participants were American football players from a variety of field positions (n=12, height =188 ± 0.01 cm, total body mass = …

Bisphenol-A And Phthalate Metabolism In Children With Neurodevelopmental Disorders, T Peter Stein, Margaret D Schluter, Robert A Steer, Xue Ming

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: The etiology of autism spectrum (ASD) and Attention Deficit/Hyperactivity (ADHD) disorders are multifactorial. Epidemiological studies have shown associations with environmental pollutants, such as plasticizers. This study focused on two of these compounds, the Bisphenol-A (BPA) and Diethylhexyl Phthalate (DEHP). The major pathway for BPA and DEHP excretion is via glucuronidation. Glucuronidation makes insoluble substances more water-soluble allowing for their subsequent elimination in urine.

HYPOTHESIS: Detoxification of these two plasticizers is compromised in children with ASD and ADHD. Consequently, their tissues are more exposed to these two plasticizers.

METHODS: We measured the efficiency of glucuronidation in three groups of children, …

Oligodendrocyte 2phatal Reveals Dynamics Of Myelin Degeneration And Repair, Timothy W. Chapman

Dartmouth College Ph.D Dissertations

Oligodendrocytes are responsible for producing myelin in the central nervous system. This lipid-rich coating along axons helps to increase action potential velocity, provide metabolic support to axons, and facilitate fine-tuning of neuronal circuitry. Demyelination and/or myelin dysfunction is widespread in neurodegenerative diseases and aging. Despite this, we know very little about how individual oligodendrocytes, or the myelin sheaths they produce, degenerate. Myelin repair, carried out by resident oligodendrocyte precursor cells (OPCs), is known to occur following myelin damage in certain contexts. We sought to investigate the cellular dynamics of oligodendrocyte degeneration and repair by developing a non-inflammatory demyelination model, combining …

Beyond The Symptom: The Biology Of Fatigue, David M. Raizen, Janet Mullington, Christelle Anaclet, Gerard Clarke, Hugo Critchley, Robert Dantzer, Ronald Davis, Kelly L. Drew, Josh Fessel, Patrick M. Fuller, Erin M. Gibson, Mary Harrington, W. Ian Lipkin, Elizabeth B. Klerman, Nancy Klimas, Anthony L. Komaroff, Walter Koroshetz, Lauren Krupp, Anna Kuppuswamy, Julie Lasselin, Laura D. Lewis, Pierre J. Magistretti, Heidi Y. Matos, Christine Miaskowski, Andrew H. Miller, Avindra Nath, Maiken Nedergaard, Mark R. Opp, Marylyn D. Ritchie, Dragana Rogulja, Asya Rolls, John D. Salamone

Psychology: Faculty Publications

A workshop titled “Beyond the Symptom: The Biology of Fatigue” was held virtually September 27–28, 2021. It was jointly organized by the Sleep Research Society and the Neurobiology of Fatigue Working Group of the NIH Blueprint Neuroscience Research Program. For access to the presentations and video recordings, see: https://neuroscienceblueprint.nih.gov/about/event/beyond-symptom-biology-fatigue. The goals of this workshop were to bring together clinicians and scientists who use a variety of research approaches to understand fatigue in multiple conditions and to identify key gaps in our understanding of the biology of fatigue. This workshop summary distills key issues discussed in this workshop and provides a …

Protocol For Optimizing Production And Quality Control Of Infective Ecohiv Virions, Hammodah Rawhi Hammodah Alfar, Daphne N. Pariser, Harry Chanzu, Smita Joshi, Daniёlle M. Coenen, Joshua Lykins, Kanakanagavalli Shravani Prakhya, Mary Jane Potash, Wei Chao, Jennifer Kelschenbach, David J. Volsky, Kelly Metcalf-Pate

Saha Cardiovascular Research Center Faculty Publications

EcoHIV is a model of HIV infection that recapitulates aspects of HIV-1 pathology in mice. However, there are limited published protocols to guide EcoHIV virion production. Here, we present a protocol for producing infective EcoHIV virions and essential quality controls. We describe steps for viral purification, titering, and multiple techniques to analyze infection efficacy. This protocol produces high infectivity in C57BL/6 mice which will aid investigators in generating preclinical data.

Hla-Ii-Dependent Neuroimmune Changes In Group A Streptococcal Necrotizing Fasciitis, Ganesh Ambigapathy, Santhosh Mukundan, Kumi Nagamoto-Combs, Colin Combs, Suba Nookala

Biomedical Sciences Faculty Publications

Streptococcus pyogenes (Group A Streptococcus, GAS) bacteria cause a spectrum of human diseases ranging from self-limiting pharyngitis and mild, uncomplicated skin infections (impetigo, erysipelas, and cellulitis) to highly morbid and rapidly invasive, life-threatening infections such as streptococcal toxic shock syndrome and necrotizing fasciitis (NF). HLA class II allelic polymorphisms are linked with differential outcomes and severity of GAS infections. The dysregulated immune response and peripheral cytokine storm elicited due to invasive GAS infections increase the risk for toxic shock and multiple organ failure in genetically susceptible individuals. We hypothesized that, while the host immune mediators regulate the immune responses against …

Characterization Of Pathological Tau Mutants, Charles J. Mcdonald

Dissertations, Theses, and Capstone Projects

Tau is a protein expressed exclusively in glia and neurons in the central nervous system and implicated in several neurogenerative diseases called “tauopathies”. Among all the tauopathies, one third is characterized by the presence of genetic mutations leading to the synthesis of tau proteins with single amino acid substitutions at specific locations and affecting protein function. While most of the initial studies have emphasize the functional role of tau as modulator of the axonal cytoskeleton, it has recently been well accepted that tau is also an intrinsically disordered protein that tends to form membraneless organelles called coacervates, due to a …

Metabolic Control Of Proliferation And Differentiation In Oligodendrocytes, Sami Sauma

Dissertations, Theses, and Capstone Projects

Oligodendrocytes (OLs) are specialized cells whose membrane extension, called myelin, wraps the axons providing insulation, trophic and metabolic support, and is essential for proper functioning of the central nervous system. Inappropriate myelin formation, damage or dysfunction of oligodendrocytes has been identified in several neurological disorders and often precedes the loss of neuronal cells. OLs derive from proliferating oligodendrocyte progenitor cells (OPCs), which exit from the cell cycle and undergo a series of transcriptional and epigenetic events, including histone post-translational modifications, resulting in morphological and functional changes. Our lab previously identified elevated levels of histone acetylation in proliferating OPCs during the …

Examining Metacognitive Access To Low-Level Ensemble Representations, Vladimir Mudragel

Dissertations, Theses, and Capstone Projects

Ensemble perception is a process that allows our sensory systems to rapidly extract summary information about the stimuli in the environment. For example, we are able to get a sense of the average number of items in a group of similar items (Burr & Ross, 2008; Halberda, Sires, & Feigenson, 2006) or the average size of a group of similar shapes of different sizes (Ariely, 2001). It is theorized that the qualitative result of ensemble perception is that it provides a gist impression of the current environment, which then enables attentional processes in the brain to determine which parts of …

A Novel Therapeutic Strategy For Alzheimer’S Disease: Sex-Dependent Mechanisms Altered By The Hdac Inhibitor Rg2833 In A Transgenic Rat Model, Kelechi Ndukwe

Dissertations, Theses, and Capstone Projects

Alzheimer’s disease (AD) is the most common cause of dementia. In the United States, AD affects about 6.2 million Americans and is projected to reach 13.8 million by 2050. Currently, there are no effective therapies for AD and therapies targeting epigenetic mechanisms have shown to be effective in improving cognitive performance in animal models of AD. However, until now no study has reported sex-dependent mechanisms leading to differential expression of genes that contribute to changes in AD pathology. From our in silico studies, we identified an FDA-approved drug, RG2833 (N-[6-(2-aminoanilino)-6-oxohexyl]-4-methylbenzamide) that penetrates the blood brain barrier and can potentially ameliorate …

Electrophysiological Signatures Of Stress Adaptability In The Bnst-Vta Pathway, Yuka Miura

Dissertations, Theses, and Capstone Projects

Chronic stress has detrimental effects on psychological and physiological health. Incapability to adapt to chronic stress can lead to depression, anxiety disorders, and addiction. The brain regions critical for reward processing share diverse physiological and molecular changes linked to depressive-like behaviors as a result of chronic stress. Cumulative evidence shows that counteraction or prevention of these alterations in neurons, occasionally in a projection-specific manner, can enhance stress adaptation or resilience.

Chronic stress induces various changes in the brain, including in the bed nucleus of the stria terminalis (BNST) and the ventral tegmental area (VTA). The neural projections from the BNST …

Automatic Analysis Of The Frequency, Vigor, And Complexity Of Spontaneous Locomotion Bouts Of Mice With Loss And Gain Of Function Of The G Protein-Coupled Receptor Smoothened In Cholinergic Neurons, Aleksandra Feshchenko

Dissertations, Theses, and Capstone Projects

Locomotion, a fundamental behavior, is classically assessed using simple metrics of velocity and total distance moved in an open field. This behavior however offers rich data about the organization and breadth of actions an animal can take while only facing limitations due to the bio-mechanical constraints of the organism. Importantly, these actions are not biased towards a particular task-solution space imposed by many behavioral paradigms. Here, to analyze motor complexity in freely ambulating mice, we developed a method for the automatic and unbiased identification of locomotor bouts which we call Bout Finder (BF). This analysis utilizes Open Feld data to …

You Hurt My Feelings: Autonomic And Behavioral Responses To Social Exclusion And The Moderating Effect Of Psychopathic Traits, Liat Kofler

Dissertations, Theses, and Capstone Projects

Humans have a fundamental need to form and maintain social connections, and thus experiencing social exclusion is extremely distressing as it threatens this basic human need. Individuals who are socially excluded often respond aggressively, not only towards their ostracizers but also towards innocent bystanders, with ostracism being implicated in extreme acts of violence such as school shootings. However, individual differences in behavior exist within the context of social exclusion as not everyone responds aggressively after being ostracized. Identifying risk factors for retaliatory aggressive behavior following experiences of social exclusion may facilitate the development of targeted interventions aimed at mitigating such …

Changes In The Epigenetic Landscape Of Oligodendrocyte Progenitor Cells With Time, David K. Dansu

Dissertations, Theses, and Capstone Projects

Most neonatal oligodendrocyte progenitors (nOPCs) give rise to myelinating oligodendrocytes during development, while a proportion are retained as proliferative undifferentiated cells in the adult brain (aOPCs). Previous studies have reported distinct properties for those two populations but the molecular mechanisms underlying these intrinsic differences are not well understood. Using RNA-sequencing and unbiased histone proteomics analysis, we identify transcripts and histone marks that are higher in aOPCs than nOPCs. The genome-wide ChIP-sequencing analysis of chromatin from aOPCs compared to nOPCs detects greater occupancy of the H4K8ac mark at loci corresponding to the higher transcript levels of oligodendrocyte-specific transcription factors and lipid …

Brainwaves, Memory, And Reward, Rebecca Mccune

Dissertations, Theses, and Capstone Projects

The development of effective educational curricula for enhancing learning involves the crucial consideration of effort and rewards. In the realm of education, teachers commonly employ rewards as motivational tools. Traditionally, these rewards are given to students as a recognition of their successful performance. However, a thought-provoking idea emerges: What if we were to extend rewards to students not solely based on accurate answers, but also on the effort they invest, even in cases where their actual response might be incorrect? Our study explores the potential impact of this approach on the way information is absorbed and subsequently retained, specifically focusing …

Attenuated Typicality Effect In Category-Based Inferences: Implications For Autism Spectrum Disorder, Janani Rajagopalan

Dissertations, Theses, and Capstone Projects

Individuals diagnosed with Autism Spectrum Disorder (ASD) often encounter challenges in assimilating atypical exemplars into their categorical prototypes, a cognitive hurdle that can impact their interpretative and integrative capacities. Addressing this problem, the present research sought to develop a robust methodological approach to reduce the effect of this disparity. We examined the elements embedded within the category's internal structure, with the intention of experimentally attenuating the pronounced typicality effect, which is often exaggerated in ASD.

Across four experiments, the thesis investigated the cognitive and neural underpinnings that shape the access to the typicality gradient intrinsic to a category's structure. The …

Reviewing Research On Down Syndrome To Then Inform And Create A Children’S Book With A Child Protagonist Who Has Down Syndrome, Trey Williams

Honors Projects

Children's literature continually evolves, requiring a steadfast commitment to align with new insights into various disabilities for genuine and accurate portrayal. This project delves into leveraging research to craft a children's book featuring Bonnie Lynn, a protagonist with Down Syndrome, recognizing the growing presence of individuals with Down Syndrome in today's society and the imperative for empathetic understanding within this community.