Medical Neurobiology Commons^™

G Protein-Coupled Receptor Kinase-2 (Grk-2) Controls Exploration Through Neuropeptide Signaling In Caenorhabditis Elegans, Kristen Davis, Christo Mitchell, Olivia Weissenfels, Jihong Bai, David M. Raizen, Michael Ailion, Irini Topalidou

Department of Neuroscience Faculty Papers

Animals alter their behavior in manners that depend on environmental conditions as well as their developmental and metabolic states. For example, C. elegans is quiescent during larval molts or during conditions of satiety. By contrast, worms enter an exploration state when removed from food. Sensory perception influences movement quiescence (defined as a lack of body movement), as well as the expression of additional locomotor states in C. elegans that are associated with increased or reduced locomotion activity, such as roaming (exploration behavior) and dwelling (local search). Here we find that movement quiescence is enhanced, and exploration behavior is reduced in …

Excessive Mechanotransduction In Sensory Neurons Causes Joint Contractures, Shang Ma, Adrienne E Dubin, Luis O Romero, Meaghan Loud, Alexandra Salazar, Sarah Chu, Nikola Klier, Sameer Masri, Yunxiao Zhang, Yu Wang, Alex T Chesler, Katherine A Wilkinson, Valeria Vásquez, Kara L Marshall, Ardem Patapoutian

Faculty, Staff and Student Publications

Distal arthrogryposis (DA) is a collection of rare disorders that are characterized by congenital joint contractures. Most DA mutations are in muscle- and joint-related genes, and the anatomical defects originate cell-autonomously within the musculoskeletal system. However, gain-of-function mutations in PIEZO2, a principal mechanosensor in somatosensation, cause DA subtype 5 (DA5) through unknown mechanisms. We show that expression of a gain-of-function PIEZO2 mutation in proprioceptive sensory neurons that mainly innervate muscle spindles and tendons is sufficient to induce DA5-like phenotypes in mice. Overactive PIEZO2 causes anatomical defects through increased activity within the peripheral nervous system during postnatal development. Furthermore, botulinum toxin …

Trogocytosis Of Neurons And Glial Cells By Microglia In A Healthy Adult Macaque Retina, Megan Goyal, Andrea S Bordt, Jay Neitz, David W Marshak

Faculty, Staff and Student Publications

Microglial cells are the primary resident immune cells in the retina. In healthy adults, they are ramified; that is, they have extensive processes that move continually. In adult retinas, microglia maintain the normal structure and function of neurons and other glial cells, but the mechanism underlying this process is not well-understood. In the mouse hippocampus, microglia engulf small pieces of axons and presynaptic terminals via a process called trogocytosis. Here we report that microglia in the adult macaque retina also engulf pieces of neurons and glial cells, but not at sites of synapses. We analyzed microglia in a volume of …

Infiltrating Cd8+ T Cells Exacerbate Alzheimer’S Disease Pathology In A 3d Human Neuroimmune Axis Model, Jefin Jose, Devam Purohit

VCU's Medical Journal Club: The Work of Future Health Professionals

In this study, Jorfi et al. employed a neuroimmune axis model containing neurons, astrocytes, and microglia to examine the role of immune cells in Alzheimer's disease. Jorfi et al. found that T cells selectively infiltrated the BRAIN compartment of the neuroimmune axis model as compared to B cells and monocytes. Jorfi et al. further found that CD8+ T cells demonstrated heightened cytotoxicity in the Alzheimer's disease brain, illuminating the role of immune cells in neurodegeneration. Upon further examination, the CXCR3-CXCL10 signaling pathway was found to have an important role in inflammation.

A Genome-Wide In Vivo Crispr Screen Identifies Essential Regulators Of T Cell Migration To The Cns In A Multiple Sclerosis Model, Jefin Jose

VCU's Medical Journal Club: The Work of Future Health Professionals

Kendirli et al. (2023) used a CRISPR screen to determine the proteins involved in T cell migration into the CNS in multiple sclerosis. Overall, eighteen facilitators and five brakes to T cell infiltration into the CNS were identified. Kendirli et al. specifically identified ITGA4, FERMT3, and HSP90B1 to make up the adhesion module, CXCR3, GNAI2, and TBX21 to make up the chemotaxis module, and GRK2 and S1PR2 to make up the egress module. This study demonstrated the ability of a CRISPR screen to identify elements in a disease process and thus identify targets for future multiple sclerosis therapies.

Precision Medicine Approach To Alzheimer’S Disease: Rationale And Implications, Dale E. Bredesen, Kat Toups, Ann Hathaway, Deborha Gordon, Henrianna Chung, Cyrus Raji, Alan Boyd, Benjamin D. Hill, Sharon Hausman-Cohen, Mouna Attarha, Won Jong Chwa, Alexei Kurakin, Michael Jarrett

University Faculty and Staff Publications

The neurodegenerative disease field has enjoyed extremely limited success in the development of effective therapeutics. One potential reason is the lack of disease models that yield accurate predictions and optimal therapeutic targets. Standard clinical trials have pre-determined a single treatment modality, which may be unrelated to the primary drivers of neurodegeneration. Recent proof-of-concept clinical trials using a precision medicine approach suggest a new model of Alzheimer’s disease (AD) as a chronic innate encephalitis that creates a network insufficiency. Identifying and addressing the multiple potential contributors to cognitive decline for each patient may represent a more effective strategy. Here we review …

Examining A Blood Biomarker Approach To Blood-Brain Barrier Disruption, Samantha Ford

Theses and Dissertations--Medical Sciences

Blood-brain barrier disruption has been identified to associate with the pathogenesis several neurological diseases such as dementia [1, 2], multiple sclerosis[3, 4], acute or chronic cerebral ischemia[5], brain trauma[5], meningitis[5], encephalitis[5], stroke[6], and seizures[7]. Being able to effectively identify blood-brain barrier disruption is limited in methodology. The current standard is using a cerebrospinal fluid (CSF) albumin to serum albumin index, which requires the use of a lumbar puncture. A novel method of identifying blood-brain barrier disruption utilizing blood biomarkers is proposed in this study. Participants in this study had previously collected blood and CSF samples, which were analyzed to compare …

Copy Number Alterations Of Aggressive Pituitary Neuroendocrine Tumors, Grace Zhang

Scripps Senior Theses

Pituitary neuroendocrine tumors (PitNETs) are tumors of the pituitary gland. Although most are benign, they can cause severe morbidity if compression of surrounding tissue and/or endocrinopathies occur.

Aggressive PitNETs are notably detrimental and difficult to predict, and their effects are further exacerbated by challenges in treatment. Although histological studies can detect certain markers of tumor aggressiveness, they are insufficient at wholly predicting PitNET aggressiveness, making the clinical behavior of PitNETs challenging to determine. Since treatment of aggressive tumors also remains suboptimal, this further results in negative impacts on health and quality of life.

Genetic markers, such as copy number variations …

Incog 2.0 Guidelines For Cognitive Rehabilitation Following Traumatic Brain Injury, Part Iii: Executive Functions, Eliyas Jeffay, Jennie Ponsford, Amber Harnett, Shannon Janzen, Eleni Patsakos, Jacinta Douglas, Mary Kennedy, Ailene Kua, Robert Teasell, Penny Welch-West, Mark Theodore Bayley, Robin Green

Communication Sciences and Disorders Faculty Articles and Research

Introduction:

Moderate-to-severe traumatic brain injury (MS-TBI) causes debilitating and enduring impairments of executive functioning and self-awareness, which clinicians often find challenging to address. Here, we provide an update to the INCOG 2014 guidelines for the clinical management of these impairments.

Methods:

An expert panel of clinicians/researchers (known as INCOG) reviewed evidence published from 2014 and developed updated recommendations for the management of executive functioning and self-awareness post-MS-TBI, as well as a decision-making algorithm, and an audit tool for review of clinical practice.

Results:

A total of 8 recommendations are provided regarding executive functioning and self-awareness. Since INCOG 2014, 4 …

Nasal Accumulation And Metabolism Of Δ9-Tetrahydrocannabinol Following Aerosol (‘Vaping’) Administration In An Adolescent Rat Model, Alexa Torrens, Christina M Ruiz, Maricela X Martinez, Alex Mabou Tagne, Pritam Roy, Dakota Grimes, Faizy Ahmed, Valeria Lallai, Victoria Inshishian, Malia Bautista, Yen-Chu Chen, Marilyn A. Huestis, Aditi Das, Christie D Fowler, Stephen V Mahler, Daniele Piomelli

Institute of Emerging Health Professions Faculty Papers

Passive aerosol exposure to Δ9-tetrahydrocannabinol (THC) in laboratory animals results in faster onset of action and less extensive liver metabolism compared to most other administration routes and might thus provide an ecologically relevant model of human cannabis inhalation. Previous studies have, however, overlooked the possibility that rodents, as obligate nose breathers, may accumulate aerosolized THC in the nasal cavity, from where the drug might directly diffuse to the brain. To test this, we administered THC (ten 5-s puffs of 100 mg/mL of THC) to adolescent (31-day-old) Sprague-Dawley rats of both sexes. We used liquid chromatography/tandem mass spectrometry to quantify the …

Incog 2.0 Guidelines For Cognitive Rehabilitation Following Traumatic Brain Injury, Part V: Memory, Diana Velikonja, Jennie Ponsford, Shannon Janzen, Amber Harnett, Eleni Patsakos, Mary Kennedy, Leanne Togher, Robert Teasell, Amanda Mcintyre, Penny Welch-West, Ailene Kua, Mark Theodore Bayley

Communication Sciences and Disorders Faculty Articles and Research

Introduction:

Memory impairments affecting encoding, acquisition, and retrieval of information after moderate-to-severe traumatic brain injury (TBI) have debilitating and enduring functional consequences. The interventional research reviewed primarily focused on mild to severe memory impairments in episodic and prospective memory. As memory is a common focus of cognitive rehabilitation, clinicians should understand and use the latest evidence. Therefore, the INCOG (“International Cognitive”) 2014 clinical practice guidelines were updated.

Methods:

An expert panel of clinicians/researchers reviewed evidence published since 2014 and developed updated recommendations for intervention for memory impairments post-TBI, a decision-making algorithm, and an audit tool for review of clinical practice. …

Incog 2.0 Guidelines For Cognitive Rehabilitation Following Traumatic Brain Injury: What’S Changed From 2014 To Now?, Mark Theodore Bayley, Shannon Janzen, Amber Harnett, Peter Bragge, Leanne Togher, Ailene Kua, Eleni Patsakos, Lyn S. Turkstra, Robert Teasell, Mary Kennedy, Shawn Marshall, Jennie Ponsford

Communication Sciences and Disorders Faculty Articles and Research

IT IS CRITICAL TO KEEP clinical practice guidelines (CPGs) up to date through integration of the latest evidence. Therefore, it is with great excitement that the INCOG team presents the INCOG 2.0 Guidelines for Cognitive Rehabilitation Following Traumatic Brain Injury (TBI). In this brief introduction, we provide an overview of changes in the evidence from 2014; share insights into the current state and challenges implementing cognitive rehabilitation; and provide an overview of INCOG 2022.

Support Their Sleep: Enhancing Nurses' Knowledge And Implementation Of Non-Pharmacological Sleep Protocols To Improve Patient Rest, Recovery, And Reduce Cognitive Impairment., David C. Barry

Master's Theses and Capstones

Background: Sleep and rest play an influential role in promoting recovery and healing in humans. Hospitalized patients are at risk for altered sleep from hospitalization, illness, and stimulation from a hospital environment. Non-pharmacologic interventions preformed by nurses can help to improve sleep and sleep environment for patients.

Local problem: There was no protocol or available information regarding patient sleep promotion for nurses to references when caring for patients.

Methods: Nurses in the microsystem (n=8) were administered a pre/post questionnaire containing Likert scales and a short quiz containing knowledge-based questions. Questionnaires were distributed to nurses prior to and after …

The Role Of The Nlrp3 Inflammasome In Alzheimer's Disease, Ethan S. Terman

Undergraduate Research Posters

This study examines the consequences of Alzheimer’s in rat and mice test subjects. The goal is to identify the effects of certain NLRP3 inhibiting drugs and to see if there are any noticeable effects in regards to impeding the pathological development of Alzheimer’s disease. The results are visualized by implementing the immunohistochemical process to identify neurodegeneration in the brain and to assess the expression levels of amyloid beta as an indicator of Alzheimer’s pathology. Other tests are also conducted on these transgenic mice to gauge cognitive functioning levels during the onset of their disease, those being behavior tests, but not …

Visualization And Characterization Of The Immunological Synapse Between Chlorotoxin Chimeric Antigen (Cltx-Car) Redirected T Cells And Targeted Glioblastoma Tumors, Arianna Livi

CMC Senior Theses

Chimeric Antigen Receptor T (CAR-T) cells have demonstrated anti-tumor activity against aggressive and invasive cancers such as glioblastoma (GBM); however, clinical response rates remain low in clinical trial studies. Tumor heterogeneity and tumor microenvironment conditions pose significant challenges for treatment of GBM, thus continuous optimization of CAR-T cell therapies and identification of novel, widely expressed, and highly specific GBM antigens are vital to better patient outcomes. A newly developed CAR-T cell construct incorporating chlorotoxin (CLTX) as the targeting domain exhibited broad GBM-targeting capabilities and elicited potent cytotoxic effects during preclinical studies and is currently being tested in a phase I …

Incog 2.0 Guidelines For Cognitive Rehabilitation Following Traumatic Brain Injury, Part Iv: Cognitive-Communication And Social Cognition Disorders, Leanne Togher, Jacinta Douglas, Lyn S. Turkstra, Penny Welch-West, Shannon Janzen, Amber Harnett, Mary Kennedy, Ailene Kua, Eleni Patsakos, Jennie Ponsford, Robert Teasell, Mark Theodore Bayley, Catherine Wiseman-Hakes

Communication Sciences and Disorders Faculty Articles and Research

Introduction:

Moderate to severe traumatic brain injury causes significant cognitive impairments, including impairments in social cognition, the ability to recognize others' emotions, and infer others' thoughts. These cognitive impairments can have profound negative effects on communication functions, resulting in a cognitive-communication disorder. Cognitive-communication disorders can significantly limit a person's ability to socialize, work, and study, and thus are critical targets for intervention. This article presents the updated INCOG 2.0 recommendations for management of cognitive-communication disorders. As social cognition is central to cognitive-communication disorders, this update includes interventions for social cognition.

Methods:

An expert panel of clinicians/researchers reviewed evidence published since …

The Future Of Incog (Is Now), Peter Bragge, Mark Theodore Bayley, Diana Velikonja, Leanne Togher, Jennie Ponsford, Shannon Janzen, Amber Harnett, Ailene Kua, Eleni Patsakos, Amanda Mcintyre, Robert Teasell, Mary Kennedy, Shawn Marshall

Communication Sciences and Disorders Faculty Articles and Research

IT HAS BEEN 8 years since the first iteration of the INCOG clinical practice guidelines (CPGs) were published. Much has happened since 2014, and a considerable body of evidence has been published in the various domains of cognitive rehabilitation research represented in this special issue. Over this time, significant developments in the science of identifying, appraising, and distilling research evidence into practically applicable CPGs have emerged, as well as implementation efforts to ensure meaningful change in care delivery.

Investigating The Effects Of Flotation Restricted Environment Stimulation Therapy On Neural Networks In Chronic Pain Patients Via Functional Magnetic Resonance Imaging And Other Modalities, Tyler Austin Mcgaughey

Graduate Theses, Dissertations, and Problem Reports (ETD)

Chronic lower back pain (CLBP) is one of the leading causes of disability worldwide, with an estimated direct cost of over 600 billion dollars in the US alone. CLBP profoundly impacts the patient, their support team, and the healthcare system. Widespread changes to the patient's well-being, including mental health, are seen in CLBP and contribute to a downward spiral that often leads to disability. Chronic pain is poorly understood and is difficult to treat because of its subjective nature. Recent improvements in pain assessment in the clinic and in biomedical research have had a profoundly impacted the field. More than …

P120-Catenin Subfamily Members Have Distinct As Well As Shared Effects On Dendrite Morphology During Neuron Development In Vitro, Maxsam S Donta, Yogesh Srivastava, Christina M Di Mauro, Adriana Paulucci-Holthauzen, M Neal Waxham, Pierre D Mccrea

Faculty, Staff and Student Publications

Dendritic arborization is essential for proper neuronal connectivity and function. Conversely, abnormal dendrite morphology is associated with several neurological pathologies like Alzheimer's disease and schizophrenia. Among major intrinsic mechanisms that determine the extent of the dendritic arbor is cytoskeletal remodeling. Here, we characterize and compare the impact of the four proteins involved in cytoskeletal remodeling-vertebrate members of the p120-catenin subfamily-on neuronal dendrite morphology. In relation to each of their own distributions, we find that p120-catenin and delta-catenin are expressed at relatively higher proportions in growth cones compared to ARVCF-catenin and p0071-catenin; ARVCF-catenin is expressed at relatively high proportions in the …

Syntaxin 3b Is A T-Snare Specific For Ribbon Synapses Of The Retina, Mariajose Perez-Hurtado, Calvin Dao, Amanda E Saenz, Ruth Heidelberger

Faculty, Staff and Student Publications

Biallelic loss-of-function mutations in the syntaxin 3 gene have been linked to a severe retinal dystrophy in humans that presents in early childhood. In mouse models, biallelic inactivation of the syntaxin 3 gene in photoreceptors rapidly leads to their death. What is not known is whether a monoallelic syntaxin 3 loss-of-function mutation might cause photoreceptor loss with advancing age. To address this question, we compared the outer nuclear layer of older adult mice (≈ 20 months of age) that were heterozygous for syntaxin 3 with those of similarly-aged control mice. We found that the photoreceptor layer maintains its thickness in …