Medical Anatomy Commons^™

Caudal Dmn Neurons Innervate The Spleen And Release Cart Peptide To Regulate Neuroimmune Function, Nobuhide Kobori, Anthony N Moore, John B Redell, Pramod K Dash

Faculty, Staff and Student Publications

BACKGROUND: Inflammation is a fundamental biological response to injury and infection, which if unregulated can contribute to the pathophysiology of many diseases. The vagus nerve, which primarily originates from the dorsal motor nucleus (DMN), plays an important role in rapidly dampening inflammation by regulating splenic function. However, direct vagal innervation of the spleen, which houses the majority of immune and inflammatory cells, has not been established. As an alternative to direct innervation, an anti-inflammatory reflex pathway has been proposed which involves the vagus nerve, the sympathetic celiac ganglion, and the neurotransmitter norepinephrine. Although sympathetic regulation of inflammation has been shown, …

Regeneration Of Neurons In Human Brain Tissue; A Revolutionary Concept With Therapeutic Potential, Mackenzie R. Dunn

Biomedical Sciences Undergraduate Research

There is current research to suggest that endogenous neuronal regeneration, exogenous neuronal stem cell transplantation and glial cell reprogramming could be prospective therapeutic treatments for neurodegeneration and traumatic injury. With these conditions, there is significant brain atrophy, loss of neurons and loss of synaptic connections which can have devastating effects on executive functioning, cognition, learning and memory. This review will examine these modern approaches to adult neurogenesis, and assess the viable mechanisms and future outlook of these three therapies for neurological regenerative medicine.

Visualizing Lipid Membrane Structure With Cryo-Em: Past, Present, And Future, Karan D Sharma, Frederick A Heberle, M Neal Waxham

Faculty, Staff and Student Publications

The development of electron cryomicroscopy (cryo-EM) has evolved immensely in the last several decades and is now well-established in the analysis of protein structure both in isolation and in their cellular context. This review focuses on the history and application of cryo-EM to the analysis of membrane architecture. Parallels between the levels of organization of protein structure are useful in organizing the discussion of the unique parameters that influence the collective behavior that influences membrane structure and function. Importantly, the timescales of lipid motion in bilayers with respect to the timescales of sample vitrification is discussed and reveals what types …

Clinical Features And Shared Mechanisms Of Chronic Gastritis And Osteoporosis, Tao Han, Yili Zhang, Baoyu Qi, Ming Chen, Kai Sun, Xiaokuan Qin, Bowen Yang, He Yin, Aili Xu, Xu Wei, Liguo Zhu

Faculty, Staff and Student Publications

Chronic gastritis (CG) and osteoporosis (OP) are common and occult diseases in the elderly and the relationship of these two diseases have been increasingly exposed. We aimed to explore the clinical characteristics and shared mechanisms of CG patients combined with OP. In the cross-sectional study, all participants were selected from BEYOND study. The CG patients were included and classified into two groups, namely OP group and non-OP group. Univariable and multivariable logistic regression methods were used to evaluate the influencing factors. Furthermore, CG and OP-related genes were obtained from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified …

Optimization Of Cryo-Electron Microscopy For Quantitative Analysis Of Lipid Bilayers, Frederick A Heberle, Doug Welsch, Haden L Scott, M Neal Waxham

Faculty, Staff and Student Publications

Cryogenic electron microscopy (cryo-EM) is among the most powerful tools available for interrogating nanoscale structure of biological materials. We recently showed that cryo-EM can be used to measure the bilayer thickness of lipid vesicles and biological membranes with subangstrom precision, resulting in the direct visualization of nanoscopic domains of different thickness in multicomponent lipid mixtures and giant plasma membrane vesicles. Despite the great potential of cryo-EM for revealing the lateral organization of biomembranes, a large parameter space of experimental conditions remains to be optimized. Here, we systematically investigate the influence of instrument parameters and image postprocessing steps on the ability …

Positioning The Brainstem Within The Neural Network Of Threat Prediction, Xu O Zhang, Fabricio H Do Monte

Faculty, Staff and Student Publications

In a recent study, Strickland and McDannald dissected the role of brainstem networks in threat prediction. Using probabilistic threat discrimination in rats, the authors demonstrated that brainstem neurons estimate threat probability and generate positive aversive prediction errors after unexpected outcomes. Their findings suggest that, beyond organizing defensive behaviors, brainstem neurons are involved in threat prediction computations.

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 …

Sp1 Trans-Activates The Murine H+-K+-Atpase Α2-Subunit Gene, Xiaobo Wang, Yili Zhang, Xiuyun Zhou, Xiumei Xia, Weijun Teng, Lin Sheng, Jing Ding

Faculty, Staff and Student Publications

Acute lung injury (ALI) followed with severe inflammation and oxidative stress. Anti-inflammatory and antioxidant are the properties of aquaporin 1 (AQP1) and aquaporin 5 (AQP5). The goal of this study was to see if soy isoflavone can diminish lipopolysaccharide (LPS)-induced ALI and the underling mechanism. LPS-induced ALI was given to Sprague-Dawley rats 14 days following oophorectomy. One hour before the LPS challenge, estradiol (1 mg/kg) was administered subcutaneously as positive control and soy isoflavone was intragastric administration for 14 days prior to LPS challenge with different doses. Six hours after LPS challenge, the pulmonary edema, pathophysiology, inflammation, and the oxidative …

Dynamics And Mechanisms Of Erk Activation After Different Protocols That Induce Long-Term Synaptic Facilitation In Aplysia, Yili Zhang, Rong-Yu Liu, Paul Smolen, Leonard J Cleary, John H Byrne

Faculty, Staff and Student Publications

Phosphorylation of the MAPK family member extracellular signal–regulated kinase (ERK) is required to induce long-term synaptic plasticity, but little is known about its persistence. We examined ERK activation by three protocols that induce long-term synaptic facilitation (LTF) of the Aplysia sensorimotor synapse – the standard protocol (five 5-min pulses of 5-HT with interstimulus intervals (ISIs) of 20 min), the enhanced protocol (five pulses with irregular ISIs, which induces greater and longer-lasting LTF) and the two-pulse protocol (two pulses with ISI 45 min). Immunofluorescence revealed complex ERK activation. The standard and two-pulse protocols immediately increased active, phosphorylated ERK (pERK), which decayed …

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 …

Alterations In Static And Dynamic Regional Homogeneity In Mesial Temporal Lobe Epilepsy With And Without Initial Precipitating Injury, Xinyue Mao, Xiaonan Zhang, Chengru Song, Keran Ma, Kefan Wang, Xin Wang, Yajun Lian, Yong Zhang, Shaoqiang Han, Jingliang Cheng, Yan Zhang

Faculty, Staff and Student Publications

Objectives

Initial precipitating injury (IPI) such as febrile convulsion and intracranial infection will increase the susceptibility to epilepsy. It is still unknown if the functional deficits differ between mesial temporal lobe epilepsy with IPI (mTLE-IPI) and without IPI (mTLE-NO).

Methods

We recruited 25 mTLE-IPI patients, 35 mTLE-NO patients and 33 healthy controls (HC). Static regional homogeneity (sReHo) and dynamic regional homogeneity (dReHo) were then adopted to estimate the alterations of local neuronal activity. One-way analysis of variance was used to analyze the differences between the three groups in sReHo and dReHo. Then the results were utilized as masks for further …

Traumatic Brain Injury-Associated Epigenetic Changes And The Risk For Neurodegenerative Diseases, Paul Smolen, Pramod K Dash, John B Redell

Faculty, Staff and Student Publications

Epidemiological studies have shown that traumatic brain injury (TBI) increases the risk for developing neurodegenerative diseases (NDs). However, molecular mechanisms that underlie this risk are largely unidentified. TBI triggers widespread epigenetic modifications. Similarly, NDs such as Alzheimer's or Parkinson's are associated with numerous epigenetic changes. Although epigenetic changes can persist after TBI, it is unresolved if these modifications increase the risk of later ND development and/or dementia. We briefly review TBI-related epigenetic changes, and point out putative feedback loops that might contribute to long-term persistence of some modifications. We then focus on evidence suggesting persistent TBI-associated epigenetic changes may contribute …

More Management Is Needed To Improve The Effectiveness Of Artificial Grassland In Vegetation And Soil Restoration On The Three-River Headwaters Region Of China, Nengyu Wang, Jiayi Wan, Mingjun Ding, Hua Zhang, Shicheng Li, Linshan Liu, Yili Zhang

Faculty, Staff and Student Publications

Establishing an artificial grassland is a common measure employed to restore heavily degraded alpine grasslands for regional sustainability. The Three-River Headwaters Region in China has significant areas of black-soil-type grassland which is typified by heavy degradation; nearly 35% of the grassland regions in the Three-River Headwaters Region has degraded into this type. There are different plant community types of black-soil-type grasslands, however, it is not clear which restoration measures should be adopted for different kinds of black-soil-type grasslands. Here, we investigate the plant community characteristics and soil physicochemical properties of artificial grasslands, two types of black-soil-type grasslands, and native undegraded …

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 …

Nursing Considerations For Post-Traumatic Amnesia After A Traumatic Brain Injury, Hannah Grant

Senior Honors Theses

A period known as post-traumatic amnesia (PTA) often follows a traumatic brain injury (TBI). PTA is characterized by anterograde and retrograde amnesia, confusion, disorientation, and agitation. The duration and severity of PTA is a key indicator of the long-term prognosis after a TBI, so proper assessment and nursing care of a PTA patient is crucial. TBIs range from mild to severe, but primarily affect the fronto-temporal lobes. In PTA, both neural lesions and white matter damage within the parahippocampal region can cause PTA. A nurse must perform a thorough assessment of a TBI patient, but, since PTA is a key …

Early Systemic Glycolytic Shift After Aneurysmal Subarachnoid Hemorrhage Is Associated With Functional Outcomes, Aaron M Gusdon, Chenlian Fu, Vasanta Putluri, Atzhiry S Paz, Hua Chen, Xuefang Ren, Mohammed Khurshidul Hassan, Pramod Dash, Cristian Coarfa, Nagireddy Putluri, Huimahn A Choi, Jude P J Savarraj

Faculty, Staff and Student Publications

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) leads to a robust systemic inflammatory response. We hypothesized that an early systemic glycolytic shift occurs after aSAH, resulting in a unique metabolic signature and affecting systemic inflammation.

METHODS: Control patients and patients with aSAH were analyzed. Samples from patients with aSAH were collected within 24 h of aneurysmal rupture. Mass spectrometry-based metabolomics was performed to assess relative abundance of 16 metabolites involved in the tricarboxylic acid cycle, glycolysis, and pentose phosphate pathway. Principal component analysis was used to segregate control patients from patients with aSAH. Dendrograms were developed to depict correlations between metabolites and …

Defective Synaptic Plasticity In A Model Of Coffin-Lowry Syndrome Is Rescued By Simultaneously Targeting Pka And Mapk Pathways, Rong-Yu Liu, Yili Zhang, Paul Smolen, Leonard J Cleary, John H Byrne

Faculty, Staff and Student Publications

Empirical and computational methods were combined to examine whether individual or dual-drug treatments can restore the deficit in long-term synaptic facilitation (LTF) of the Aplysia sensorimotor synapse observed in a cellular model of Coffin–Lowry syndrome (CLS). The model was produced by pharmacological inhibition of p90 ribosomal S6 kinase (RSK) activity. In this model, coapplication of an activator of the mitogen-activated protein kinase (MAPK) isoform ERK and an activator of protein kinase A (PKA) resulted in enhanced phosphorylation of RSK and enhanced LTF to a greater extent than either drug alone and also greater than their additive effects, which is termed …

Epigenetic Modifications And Their Potential Contribution To Traumatic Brain Injury Pathobiology And Outcome, Laura Zima, Rebecca West, Paul Smolen, Nobuhide Kobori, Georgene Hergenroeder, Huimahn A Choi, Anthony N Moore, John B Redell, Pramod K Dash

Faculty, Staff and Student Publications

Epigenetic information is not permanently encoded in the DNA sequence, but rather consists of reversible, heritable modifications that regulate the gene expression profile of a cell. Epigenetic modifications can result in cellular changes that can be long lasting and include DNA methylation, histone methylation, histone acetylation, and RNA methylation. As epigenetic modifications are reversible, the enzymes that add (epigenetic writers), the proteins that decode (epigenetic readers), and the enzymes that remove (epigenetic erasers) these modifications can be targeted to alter cellular function and disease biology. While epigenetic modifications and their contributions are intense topics of current research in the context …

Synaptic Origins Of The Complex Receptive Field Structure In Primate Smooth Monostratified Retinal Ganglion Cells, Andrea S Bordt, Sara S Patterson, James A Kuchenbecker, Marcus A Mazzaferri, Joel N Yearick, Emma R Yang, Judith Mosinger Ogilvie, Jay Neitz, David W Marshak

Faculty, Staff and Student Publications

Ganglion cells are the projection neurons of the retina. Intrinsically photosensitive retinal ganglion cells (ipRGCs) express the photopigment melanopsin and also receive input from rods and cones via bipolar cells and amacrine cells. In primates, multiple types of ipRGCs have been identified. The ipRGCs with somas in the ganglion cell layer have been studied extensively, but less is known about those with somas in the inner nuclear layer, the "displaced" cells. To investigate their synaptic inputs, three sets of horizontal, ultrathin sections through central macaque retina were collected using serial block-face scanning electron microscopy. One displaced ipRGC received nearly all …

Computational Analysis Of Memory Consolidation Following Inhibitory Avoidance (Ia) Training In Adult And Infant Rats: Critical Roles Of Camkiia And Mecp2, Yili Zhang, Paul Smolen, Cristina M Alberini, Douglas A Baxter, John H Byrne

Faculty, Staff and Student Publications

Key features of long-term memory (LTM), such as its stability and persistence, are acquired during processes collectively referred to as consolidation. The dynamics of biological changes during consolidation are complex. In adult rodents, consolidation exhibits distinct periods during which the engram is more or less resistant to disruption. Moreover, the ability to consolidate memories differs during developmental periods. Although the molecular mechanisms underlying consolidation are poorly understood, the initial stages rely on interacting signaling pathways that regulate gene expression, including brain-derived neurotrophic factor (BDNF) and Ca²⁺/calmodulin-dependent protein kinase II α (CaMKIIα) dependent feedback loops. We investigated the ways …

More Than Just Statics: Static And Temporal Dynamic Changes In Intrinsic Brain Activity In Unilateral Temporal Lobe Epilepsy, Chengru Song, Xiaonan Zhang, Shaoqiang Han, Keran Ma, Kefan Wang, Xinyue Mao, Yajun Lian, Xianchang Zhang, Jinxia Zhu, Yong Zhang, Jingliang Cheng

Faculty, Staff and Student Publications

BACKGROUND: Temporal lobe epilepsy (TLE) is the most prevalent refractory focal epilepsy and is more likely accompanied by cognitive impairment. The fully understanding of the neuronal activity underlying TLE is of great significance.

OBJECTIVE: This study aimed to comprehensively explore the potential brain activity abnormalities affected by TLE and detect whether the changes were associated with cognition.

METHODS: Six static intrinsic brain activity (IBA) indicators [amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo), degree centrality (DC), global signal correlation (GSCorr), and voxel-mirrored homotopic connectivity (VMHC)] and their corresponding dynamic indicators, such as dynamic ALFF (dALFF), dynamic fALFF …

Machine Learning Classification Of Traumatic Brain Injury Patients Versus Healthy Controls Using Arterial Spin Labeled Perfusion Mri, Vanessa I. Grass

Dissertations, Theses, and Capstone Projects

Traumatic brain injury (TBI) is one of the most common causes of death and disability worldwide, yet accurate in vivo detection of TBI neuropathology remains challenging due to complexities in the structural and functional changes observed post-injury as well as limitations in conventional neuroimaging modalities. Although advanced neuroimaging techniques such as arterial spin labeling (ASL) can noninvasively assess cerebral blood flow (CBF) changes observed post-injury, this technique is underutilized in TBI research partly due to the low signal-to-noise-ratio (SNR) inherent in ASL imaging. The aim of the current study is to examine the use of machine learning, specifically a Support …

Neurophysiology Of Space Medicine: A Literature Review, Jose R. Velasquez

MEDI 9331 Scholarly Activities Clinical Years

Space medicine is becoming an essential and expanding clinical discipline. Acquiring a deeper and complete picture understanding of the multi-systemic response due to space on human health and function is essential to ensure the success of future space exploration. A comprehensive review of the literature was performed using PubMed and focused on the current neurophysiologic findings of the central nervous system’s response to space. Ground-based analogues, which mimic the effects of microgravity, and actual spaceflight studies have been used to analyze these physiologic adaptations to space. Overall, cerebellar, sensorimotor and vestibular brain regions seem to be affected the most. Through …

Dynamic Blood-Brain Barrier Regulation In Mild Traumatic Brain Injury, Eoin O'Keeffe, Eoin Kelly, Yuzhe Liu, Chiara Giordano, Eugene Wallace, Mark Hynes, Stephen Tiernan, Aidan Meagher, Chris Greene, Stephanie Hughes, Tom Burke, John Kealy, Niamh Doyle, Alison Hay, Michael Farrell, Gerald A. Grant, Alon Friedman, Ronel Veksler, Michael G. Molloy, James F. Meaney, Niall Pender, David Camarillo, Colin P. Doherty, Matthew Campbell

Articles

Whereas the diagnosis of moderate and severe traumatic brain injury (TBI) is readily visible on current medical imaging paradigms (magnetic resonance imaging [MRI] and computed tomography [CT] scanning), a far greater challenge is associated with the diagnosis and subsequent management of mild TBI (mTBI), especially concussion which, by definition, is characterized by a normal CT. To investigate whether the integrity of the blood-brain barrier (BBB) is altered in a high-risk population for concussions, we studied professional mixed martial arts (MMA) fighters and adolescent rugby players. Additionally, we performed the linear regression between the BBB disruption defined by increased gadolinium contrast …

The Migration And Developmental Remodeling Of Intrinsic Interneurons In Visual Thalamus And The Role Of Retinal Signaling., Naomi E. Charalambakis

Electronic Theses and Dissertations

The dorsal lateral geniculate nucleus (dLGN) of the mouse is a model system to study the development of thalamic circuitry. While most studies focus on relay neurons of dLGN, little is known about the factors regulating the development of the other principal cell type, intrinsic interneurons. To date, the targeting and migratory path of dLGN interneurons as well as their morphological development remains unclear. Here we examined whether the migration, structure, and function of interneurons relies on retinal signaling. We took a loss-of-function approach and crossed GAD67-GFP mice, which express green fluorescent protein (GFP) in dLGN interneurons, with math5 nulls …

Spinal Cord Trauma: An Overview Of Normal Structure And Function, Primary And Secondary Mechanisms Of Injury, And Emerging Treatment Modalities, Daniel Morin

Senior Honors Theses

The structures of the spinal cord and vertebral column are designed to provide flexibility, while still providing ample protection for the spinal cord deep within. While it does offer remarkable protection against most routine trauma, the spinal cord is still vulnerable to high-force etiologies of trauma and may become damaged as a result. These events are referred to as primary injury. Following the initial injury, the body’s own physiological responses cause a cascade of deleterious effects, known as secondary injury. Secondary injury is a major therapeutic target in mitigating the effects of spinal cord injury (SCI), and much research is …

Three-Dimensional Imaging Of Kndy Neurons In The Mammalian Brain Using Optical Tissue Clearing And Multiple-Label Immunocytochemistry, Aleisha M. Moore, Kathryn A. Lucas, Robert L. Goodman, Lique M. Coolen, Michael N. Lehman

Faculty & Staff Scholarship

Kisspeptin/Neurokinin B/Dynorphin (KNDy) neurons of the arcuate nucleus (ARC) play a key role in the regulation of fertility. The ability to detect features of KNDy neurons that are essential for fertility may require three-dimensional (3D) imaging of the complete population. Recently developed protocols for optical tissue clearing permits 3D imaging of neuronal populations in un-sectioned brains. However, these techniques have largely been described in the mouse brain. We report 3D imaging of the KNDy cell population in the whole rat brain and sheep hypothalamus using immunolabelling and modification of a solvent-based clearing protocol, iDISCO. This study expands the use of …

Amidated Dopamine Neuron Stimulating Peptides For Cns Dopaminergic Upregulation, Luke H. Bradley, Don M. Gash, Greg A. Gerhardt

Neuroscience Faculty Patents

The present invention relates to novel proteins, referred to herein as amidated glial cell line-derived neurotrophic factor (GDNF) peptides (or "Amidated Dopamine Neuron Stimulating peptides (ADNS peptides)"), that are useful for treating brain diseases and injuries that result in dopaminergic deficiencies.

Amidated Dopamine Neuron Stimulating Peptide Restoration Of Mitochondrial Activity, Luke H. Bradley, Don M. Gash, Greg A. Gerhardt

Neuroscience Faculty Patents

The present invention relates to the use of novel proteins, referred to herein as amidated glial cell line-derived neurotrophic factor (GDNF) peptides (or “Amidated Dopamine Neuron Stimulating peptides (ADNS peptides)”), for treating brain diseases and injuries that result in dopaminergic deficiencies and mitochodrial dysfunction, e.g., reduced complex I enzyme activity.

Therapy Options For Winged Scapula Patients: A Literature Review, Samantha L. Normand

Honors Undergraduate Theses

Winged scapula is a condition characterized by lateral or medial protrusion of the scapula caused by nerve damage leading to muscular paralysis. The purpose of this systematic review of literature is to evaluate the current research literature related to the effectiveness of therapy options for winged scapula. Eleven peer reviewed English language research articles published from 1998 to present were included for evaluation. Study results revealed positive therapeutic outcomes for physical therapy and scapular bracing. Results also showed positive outcomes for the use of transcutaneous electrical nerve stimulation and acupuncture for the treatment of nerve related conditions similar to winged …