Neurosciences Commons^™

Nanoscale Rules Governing The Organization Of Glutamate Receptors In Spine Synapses Are Subunit Specific, Martin Hruska, Rachel E Cain, Matthew B Dalva

Department of Neuroscience Faculty Papers

Heterotetrameric glutamate receptors are essential for the development, function, and plasticity of spine synapses but how they are organized to achieve this is not known. Here we show that the nanoscale organization of glutamate receptors containing specific subunits define distinct subsynaptic features. Glutamate receptors containing GluA2 or GluN1 subunits establish nanomodular elements precisely positioned relative to Synaptotagmin-1 positive presynaptic release sites that scale with spine size. Glutamate receptors containing GluA1 or GluN2B specify features that exhibit flexibility: GluA1-subunit containing AMPARs are found in larger spines, while GluN2B-subunit containing NMDARs are enriched in the smallest spines with neither following a strict …

Complexes Of Ghrelin Ghs-R1a, Ghs-R1b, And Dopamine D1 Receptors Localized In The Ventral Tegmental Area As Main Mediators Of The Dopaminergic Effects Of Ghrelin, Gemma Navarro, William Rea, César Quiroz, Estefanía Moreno, Devan Gomez, Cody J. Wenthur, Vicent Casadó, Lorenzo Leggio, Matthew C. Hearing, Sergi Ferré

Biomedical Sciences Faculty Research and Publications

Ghrelin receptor, also known as growth hormone secretagogue receptor (GHS-R1a), is coexpressed with its truncated isoform GHS-R1b, which does not bind ghrelin or signal, but oligomerizes with GHS-R1a, exerting a complex modulatory role that depends on its relative expression. D₁ dopamine receptor (D1R) and D5R constitute the two D₁-like receptor subtypes. Previous studies showed that GHS-R1b also facilitates oligomerization of GHS-R1a with D1R, conferring GHS-R1a distinctive pharmacological properties. Those include a switch in the preferred coupling of GHS-R1a from Gq to Gs and the ability of D1R/D5R agonists and antagonists to counteract GHS-R1a signaling. Activation of ghrelin …

Early Morphological Changes Of The Rectus Femoris Muscle And Deep Fascia In Ullrich Congenital Muscular Dystrophy, Patrizia Sabatelli, Luciano Merlini, Alberto Di Martino, Vittoria Cenni, Cesare Faldini

Department of Medicine Faculty Papers

Ullrich congenital muscular dystrophy (UCMD) is a severe form of muscular dystrophy caused by the loss of function of collagen VI, a critical component of the muscle-tendon matrix. Magnetic resonance imaging of UCMD patients’ muscles shows a peculiar rim of abnormal signal at the periphery of each muscle, and a relative sparing of the internal part. The mechanism/s involved in the early fat substitution of muscle fiber at the periphery of muscles remain elusive. We studied a muscle biopsy of the rectus femoris/deep fascia (DF) of a 3-year-old UCMD patient, with a homozygous mutation in the COL6A2 gene. By immunohistochemical …

Craniofacial Fluctuating Asymmetry In Gorillas, Chimpanzees, And Macaques, Ashly N. Romero, D. Rex Mitchell, Siobhán B. Cooke, Claire A. Kirchhoff, Claire E. Terhune

Biomedical Sciences Faculty Research and Publications

Objectives

Craniofacial fluctuating asymmetry (FA) refers to the random deviations from symmetry exhibited across the craniofacial complex and can be used as a measure of developmental instability for organisms with bilateral symmetry. This article addresses the lack of data on craniofacial FA in nonhuman primates by analyzing FA magnitude and variation in chimpanzees, gorillas, and macaques. We offer a preliminary investigation into how FA, as a proxy for developmental instability, varies within and among nonhuman primates.

Materials and Methods

We generated 3D surface models of 121 crania from Pan troglodytes troglodytes, Gorilla gorilla gorilla, and Macaca fascicularis fascicularis …

Selective Gsk3Β Inhibition Mediates An Nrf2-Independent Anti-Inflammatory Microglial Response, Mohamed H. Yousef

Theses and Dissertations

Glycogen Synthase Kinase 3 (GSK3) is associated with the proinflammatory phenotype of microglia and has been shown to act in concert with Nuclear factor kappa B (NF-κB). . GSK3 is also a suppressor of Nuclear factor erythroid 2-related factor 2 (Nrf2), the principal regulator of redox homeostasis. Agreeing with the oxidative paradigm of aging, Nrf2 is often deregulated in parainflammatory and neurodegenerative diseases. In this study, we aimed to explore a multimodal disease-modifying utility of GSK3 inhibition, beyond neuronal proteopathologies, Furthermore, we aimed to underscore the difference in therapeutic value between the two GSK3 paralogs by isoform-selective chemical inhibition.

The …

Aneurysmal Subarachnoid Hemorrhage And Acute Subdural Hematoma, Neurosurgical And Endovascular Rescue. Case Report., José Omar Santellan Resident, José Ramón Aguilar Dr., Abraham Ibarra Dr., Ulises García Dr.

Archives of Neurosurgery

Introduction: Acute subdural hemorrhage (aSDH) in association with aneurismal subarachnoid hemorrhage (SAH) is a severe disease with an incidence of 0.5% to 7.9% of all SAH. Due to the rarity of aneurysmal aSDH, it remains difficult to define a comprehensive management protocol. In this case review, following the CARE guidelines, we show the hybrid management of this pathology to know the importance of using different types of neurosurgical treatments in case of two severe diseases in critical patients.

We present two patients who developed sudden onset cephalea and neurological impairment secondary to aneurysmal subarachnoid hemorrhage associated with acute subdural hematoma. …

Consciousness Explained Or Described?, Aaron Schurger, Michael S. A. Graziano

Psychology Faculty Articles and Research

Consciousness is an unusual phenomenon to study scientifically. It is defined as a subjective, first-person phenomenon, and science is an objective, third-person endeavor. This misalignment between the means—science—and the end—explaining consciousness—gave rise to what has become a productive workaround: the search for ‘neural correlates of consciousness’ (NCCs). Science can sidestep trying to explain consciousness and instead focus on characterizing the kind(s) of neural activity that are reliably correlated with consciousness. However, while we have learned a lot about consciousness in the bargain, the NCC approach was not originally intended as the foundation for a true explanation of consciousness. Indeed, it …

Short Chain Fatty Acids Taken At Time Of Thrombectomy In Acute Ischemic Stroke Patients Are Independent Of Stroke Severity But Associated With Inflammatory Markers And Worse Symptoms At Discharge, Nicholas Henry, Jacqueline A. Frank, Christopher J. Mclouth, Amanda L. Trout, Andrew J. Morris, Jianzhong Chen, Ann M. Stowe, Justin F. Fraser, Keith R. Pennypacker

Behavioral Science Faculty Publications

Introduction: Short chain fatty acids (SCFA) are gut microbiota-derived metabolites that contribute to the gut-brain axis and may impact stroke outcomes following gut dysbiosis. We evaluated plasma SCFA concentrations against stroke severity parameters and identified SCFA-associated protein networks.

Methods: The Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC), a continuously enrolling tissue bank, was used to obtain stroke samples. Arterial blood distal and proximal to the thrombus was obtained from Acute Ischemic Stroke (AIS) Patients (n=53) during thrombectomy. Patient demographics, stroke presentation and outcome parameters were reported. The SCFAs were isolated from proximal plasma via chemical derivatization UHPLC coupled tandem …

Transcranial Direct Current Stimulation On Parkinson’S Disease: Systematic Review And Meta-Analysis, Paloma Cristina Alves De Oliveira, Thiago Anderson Brito De Araújo, Daniel Gomes Da Silva Machado, Abner Cardoso Rodrigues, Marom Bikson, Suellen Marinho Andrade, Alexandre Hideki Okano, Hougelle Simplicio, Rodrigo Pegado, Edgard Morya

Publications and Research

Background: Clinical impact of transcranial direct current stimulation (tDCS) alone for Parkinson’s disease (PD) is still a challenge. Thus, there is a need to synthesize available results, analyze methodologically and statistically, and provide evidence to guide tDCS in PD.

Objective: Investigate isolated tDCS effect in different brain areas and number of stimulated targets on PD motor symptoms.

Methods: A systematic review was carried out up to February 2021, in databases: Cochrane Library, EMBASE, PubMed/MEDLINE, Scopus, and Web of science. Full text articles evaluating effect of active tDCS (anodic or cathodic) vs. sham or control on motor symptoms of PD were …

Toward A Multimodal Computer-Aided Diagnostic Tool For Alzheimer’S Disease Conversion, Danilo Pena, Jessika Suescun, Mya Schiess, Timothy M. Ellmore, Luca Giancardo, Alzheimer’S Disease Neuroimaging Initiative

Publications and Research

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder. It is one of the leading sources of morbidity and mortality in the aging population AD cardinal symptoms include memory and executive function impairment that profoundly alters a patient’s ability to perform activities of daily living. People with mild cognitive impairment (MCI) exhibit many of the early clinical symptoms of patients with AD and have a high chance of converting to AD in their lifetime. Diagnostic criteria rely on clinical assessment and brain magnetic resonance imaging (MRI). Many groups are working to help automate this process to improve the clinical workflow. Current …

Effects Of The Selective Gsk3b Inhibitor, Tideglusib, On Ethanol Consumption, Anxiety-Like Behavior, Taste Preference, And Downstream Proteins, Sam Gottlieb, Douglas Bledsoe, Jessica L. Maltman, Alanna Morgan, Jennifer T. Wolstenholme, Michael F. Miles

Graduate Research Posters

Background: We have shown modulations in glycogen synthase kinase 3 beta (GSK3B) abundance or activity regulate ethanol consumption, suggesting potential as a therapeutic target for alcohol use disorder (AUD). Here we report the GSK3B inhibitor tideglusib’s actions on ethanol consumption, basal behaviors, and modulation of GSK3B targets.

Methods: C57BL/6J males and females received i.g. 200mg/kg tideglusib, except drinking-in-the-dark (males;100mg/kg i.p.). Drinking-in-the-dark (DID): Mice given 20% ethanol 4-hours, 4-days/week x 3 weeks and then i.p. tideglusib or vehicle x 4 days in a Latin Square design with ethanol consumption measured daily. Light/Dark Box: Mice gavaged with tideglusib or vehicle …

Emotional Component Of Pain Perception In The Medicinal Leech?, Brian D. Burrell

Animal Sentience

Crump et al. have provided a series of criteria to assess animal sentience that is focused on the perception of pain, which is known to have both sensory and emotional components. They also provide a qualitative scoring system to assess data that address the eight criteria and apply this paradigm to decapod crustaceans. The criteria laid out have the potential to be applied to other invertebrates typically thought to have sensory response to tissue damage, but no emotional component to pain perception.

Investigating The Effects Of In-Vivo Therapeutics Hypoxia Treatment Paradigms In Neurite Outgrowth Patterns, Jae Hyun Yoo

Theses and Dissertations--Medical Sciences

Spinal cord injury, specifically in the cervical C3-C4 region of the cervical spine, contributes to impaired breathing and a diminished quality of life. Therefore it is important to find effective and safe therapeutics to restore breathing function. Indeed, there are a myriad of research being performed in addition to valuable collaboration amongst different institutions. As such, inspired by a previous experiment, we decided to test our hypothesis that an enriching environment consisting of different hypoxic environments - sustained and intermittent hypoxia alongside normoxia - would result in neurite outgrowth. Moreover, we hypothesized that sustained hypoxia would result in the greatest …

Delayed Testosterone Treatment In A Rodent Model Of Repeat Mild Traumatic Brain Injury Attenuates Mechanisms Of Cellular Death In The Vestibular Nucleus, Michael Volyanyuk

Master's Theses

A common complaint after repetitive mild traumatic brain injury (rmTBI) is vestibular dysfunction, which can become persistent and decrease quality of life. Delayed testosterone treatment has been shown to reduce vestibular impairment and improve neuronal survival in the vestibular nucleus following rmTBI; however, the long-term molecular pathways associated with rmTBI and testosterone treatment remain widely unexplored. We utilized a 5-hit closed-head rodent rmTBI model and administered testosterone 35 days after injury (DPI). The vestibular nuclei were removed and prepared for RT-qPCR and western blotting. Gene expression and protein levels were elevated for markers of oxidative stress (NADPH oxidase 4) and …

Evaluating The Microbiome To Boost Recovery From Stroke: The Embrs Study, Tyler Hammond

Theses and Dissertations--Neuroscience

Accumulating evidence suggests that gut microbes modulate brain plasticity via the bidirectional gut-brain axis and may play a role in stroke rehabilitation. A severely imbalanced microbial community has been shown to occur following stroke, causing a systemic flood of neuro- and immunomodulatory substances due to increased gut permeability and decreased gut motility. Here we measure post-stroke increased gut dysbiosis and how it correlates with gut permeability and subsequent cognitive impairment.

We recruited 12 participants with acute stroke, 12 healthy control participants, and 18 participants who had risk factors for stroke, but had not had a stroke. We measured the gut …

Evaluating The Role Of Mmp9 In Hyperhomocysteinemia Induced Cerebrovascular Pathology, Alexandria Linton

Theses and Dissertations--Neuroscience

Vascular contributions to cognitive impairment and dementia (VCID) is one of the leading causes of dementia, along with Alzheimer’s disease (AD), and often manifests as a comorbidity of AD. Elevated plasma homocysteine, known as hyperhomocysteinemia (HHcy), is a risk factor for VCID; however, the mechanism underlying the connection between HHcy and development of VCID pathology remains elusive. Understanding this mechanism would reveal novel therapeutic targets with the potential to be disease modifying, which are a critical need for a disease that lacks any approved treatment. Previous studies from our lab have strongly associated neuroinflammation and blood brain barrier (BBB) dysregulation …

Current And Novel Neuroregenerative Therapies, Arrin Brooks

Theses, Dissertations and Capstones

Underlying the physical and cognitive deficits consequent of many neuropathologies is one common factor, the loss of neurons. While neurodegenerative diseases, stroke, and traumatic brain injury arise from a variety of etiologies, they all ultimately result in injury and/or death of neuronal cells and concomitant functional deficits. In the present work we primarily focus on current and potential treatments for localized lesions, particularly those in the striatum of Parkinson’s disease (PD) or the cortex as in stroke. First, we discuss a new surgical technique for deep brain stimulator (DBS) placement, as DBS is a mainstay treatment for movement disorders including …

Autonomous And Non-Autonomous Requirements For The C-Jun N-Terminal Kinase Signaling Pathway In Early Forebrain Development, Jessica G. Cunningham

Graduate Theses, Dissertations, and Problem Reports

The cerebral cortex is responsible for a wide variety of high-level functions including cognition, sensory perception, fine motor control, and the orchestration of body movements. The cortex is comprised of cortical excitatory neurons and inhibitory interneurons, which are arranged in a highly organized fashion into different layers and regions. These two types of cells operate in a delicate balance between excitation and inhibition, which is critical for proper cortical circuitry. In order for the cortex to execute its numerous functions, it must both send and receive input to other brain regions through axonal connections. The organization within the cortex and …

Uncovering The Role Of Apoe4 On Alzheimer’S Disease-Related Neuroinflammation, Courtney Marie Kloske

Theses and Dissertations--Physiology

Alzheimer’s disease (AD) is the most common neurodegenerative disease and is characterized by two hallmark pathologies: amyloid-beta plaques (Ab plaques) and hyperphosphorylated, aggregated tau tangles. These pathologies are typically accompanied by the presence of neuroinflammation which is primarily mediated by microglia. Interestingly, several genetic risk factors that increase the risk of AD also have direct impacts on neuroinflammation. Of interest, Apolipoprotein E (ApoE) is the largest genetic risk factor for AD. ApoE has three isoforms- E4 confers an increased risk for AD, E3 is considered the “control” phenotype, and E2 is protective against AD. E4 plays a role in virtually …

Evaluating The Relationship Between Plasma Biomarkers And Dementia Using Hierarchical Clustering Analysis And Linear Modeling, Zachary Winder

Theses and Dissertations--Physiology

Dementia is a disorder characterized by a significant decline from baseline in one or more cognitive domains that interferes with independence. Prevalence of dementia worldwide is estimated at 50 million people, with that number expected to triple by 2030, coming with a cost of roughly $2 trillion. Clinically, dementia is diagnosed using cognitive evaluations, with varying domains affected and to different degrees depending on the underlying pathology and stage of disease. Alzheimer’s disease (AD) and vascular contributions to cognitive impairment and dementia (VCID) are the two leading causes of dementia, and both have pathologies which can be visualized using MRI. …