Medical Physiology Commons^™

Hcn2 Channels In The Ventral Tegmental Area Regulate Behavioral Responses To Chronic Stress, Peng Zhong, Casey R. Vickstrom, Xiaojie Liu, Ying Hu, Laikang Yu, Han-Gang Yu, Qing-Song Liu

Faculty & Staff Scholarship

Dopamine neurons in the ventral tegmental area (VTA) are powerful regulators of depression-related behavior. Dopamine neuron activity is altered in chronic stress-based models of depression, but the underlying mechanisms remain incompletely understood. Here, we show that mice subject to chronic mild unpredictable stress (CMS) exhibit anxiety- and depressive-like behavior, which was associated with decreased VTA dopamine neuron firing in vivo and ex vivo. Dopamine neuron firing is governed by voltage-gated ion channels, in particular hyperpolarization- activated cyclic nucleotide-gated (HCN) channels. Following CMS, HCN-mediated currents were decreased in nucleus accumbens-projecting VTA dopamine neurons. Furthermore, shRNA-mediated HCN2 knockdown in the VTA was …

Sympatho-Excitatory Response To Pulmonary Chemosensitive Spinal Afferent Activation In Anesthetized, Vagotomized Rats, Julia A. Shanks, Zhiqiu Xia, Steven J. Lisco, George J. Rozanski, Harold D. Schultz, Irving H. Zucker, Han-Jun Wang

Journal Articles: Cellular & Integrative Physiology

The sensory innervation of the lung is well known to be innervated by nerve fibers of both vagal and sympathetic origin. Although the vagal afferent innervation of the lung has been well characterized, less is known about physiological effects mediated by spinal sympathetic afferent fibers. We hypothesized that activation of sympathetic spinal afferent nerve fibers of the lung would result in an excitatory pressor reflex, similar to that previously characterized in the heart. In this study, we evaluated changes in renal sympathetic nerve activity (RSNA) and hemodynamics in response to activation of TRPV1-sensitive pulmonary spinal sensory fibers by agonist application …

Rhythm: An Open Source Imaging Toolkit For Cardiac Panoramic Optical Mapping, Christopher Gloschat, Kedar Aras, Shubnam Gupta, N. Rokhana Faye, Hanyu Zhang, Matthew W. Kay, Igor R Efimov, +Several Additional Authors

Pharmacology and Physiology Faculty Publications

Fluorescence optical imaging techniques have revolutionized the field of cardiac electrophysiology and advanced our understanding of complex electrical activities such as arrhythmias. However, traditional monocular optical mapping systems, despite having high spatial resolution, are restricted to a two-dimensional (2D) field of view. Consequently, tracking complex three-dimensional (3D) electrical waves such as during ventricular fibrillation is challenging as the waves rapidly move in and out of the field of view. This problem has been solved by panoramic imaging which uses multiple cameras to measure the electrical activity from the entire epicardial surface. However, the diverse engineering skill set and substantial resource …

Direct Conversion Of Mouse Astrocytes Into Neural Progenitor Cells And Specific Lineages Of Neurons, Kangmu Ma, Xiaobei Deng, Xiaohuan Xia, Zhaohuan Fan, Xinrui Qi, Yongxiang Wang, Yuju Li, Yizhao Ma, Qiang Chen, Hui Peng, Jianqing Ding, Chunhong Li, Yunlong Huang, Changhai Tian, Jialin C. Zheng

Journal Articles: Cellular & Integrative Physiology

Background: Cell replacement therapy has been envisioned as a promising treatment for neurodegenerative diseases. Due to the ethical concerns of ESCs-derived neural progenitor cells (NPCs) and tumorigenic potential of iPSCs, reprogramming of somatic cells directly into multipotent NPCs has emerged as a preferred approach for cell transplantation.

Methods: Mouse astrocytes were reprogrammed into NPCs by the overexpression of transcription factors (TFs) Foxg1, Sox2, and Brn2. The generation of subtypes of neurons was directed by the force expression of cell-type specific TFs Lhx8 or Foxa2/Lmx1a.

Results: Astrocyte-derived induced NPCs (AiNPCs) share high similarities, including the expression of NPC-specific genes, DNA methylation …

Novel Antioxidant Properties Of Doxycycline, Dahn L. Clemens, Michael J. Duryee, Cleofes Sarmiento, Andrew Chiou, Jacob D. Mcgowan, Carlos D. Hunter, Sarah L. Schlichte, Jun Tian, Lynell W. Klassen, James R. O'Dell, Geoffrey M. Thiele, Ted R. Mikuls, Matthew C. Zimmerman, Daniel R. Anderson

Journal Articles: Cellular & Integrative Physiology

Doxycycline (DOX), a derivative of tetracycline, is a broad-spectrum antibiotic that exhibits a number of therapeutic activities in addition to its antibacterial properties. For example, DOX has been used in the management of a number of diseases characterized by chronic inflammation. One potential mechanism by which DOX inhibits the progression of these diseases is by reducing oxidative stress, thereby inhibiting subsequent lipid peroxidation and inflammatory responses. Herein, we tested the hypothesis that DOX directly scavenges reactive oxygen species (ROS) and inhibits the formation of redox-mediated malondialdehyde-acetaldehyde (MAA) protein adducts. Using a cell-free system, we demonstrated that DOX scavenged reactive oxygen …

S-Nitrosation Of Protein Phosphatase 1 Mediates Alcohol-Induced Ciliary Dysfunction, Michael E. Price, Adam J. Case, Jacqueline A. Pavlik, Jane M. Devasure, Todd A. Wyatt, Matthew C. Zimmerman, Joseph H. Sisson

Journal Articles: Cellular & Integrative Physiology

Alcohol use disorder (AUD) is a strong risk factor for development and mortality of pneumonia. Mucociliary clearance, a key innate defense against pneumonia, is perturbed by alcohol use. Specifically, ciliated airway cells lose the ability to increase ciliary beat frequency (CBF) to β-agonist stimulation after prolonged alcohol exposure. We previously found that alcohol activates protein phosphatase 1 (PP1) through a redox mechanism to cause ciliary dysfunction. Therefore, we hypothesized that PP1 activity is enhanced by alcohol exposure through an S-nitrosothiol-dependent mechanism resulting in desensitization of CBF stimulation. Bronchoalveolar S-nitrosothiol (SNO) content and tracheal PP1 activity was increased in wild-type (WT) …

Flexor Dysfunction Following Unilateral Transient Ischemic Brain Injury Is Associated With Impaired Locomotor Rhythmicity, Kiril Tuntevski

Graduate Theses, Dissertations, and Problem Reports (ETD)

Functional motor deficits in hemiplegia after stroke are predominately associated with flexor muscle impairments in animal models of ischemic brain injury, as well as in clinical findings. Rehabilitative interventions often employ various means of retraining a maladapted central pattern generator for locomotion. Yet, holistic modeling of the central pattern generator, as well as applications of such studies, are currently scarce. Most modeling studies rely on cellular neural models of the intrinsic spinal connectivity governing ipsilateral flexor-extensor, as well as contralateral coupling inherent in the spinal cord. Models that attempt to capture the general behavior of motor neuronal populations, as well …

Influence Of Resistance Training On Vascular Function, Hemodynamic, And Perceived Exertion Responses To Fixed Submaximal Workloads In Patients With Coronary Disease, Kerstin Grafe

Master's Theses and Doctoral Dissertations

PURPOSE: To determine the impact of superimposed resistance training (RT) in aerobically trained coronary patients on systolic blood pressure (SBP), heart rate (HR), rating of perceived exertion (RPE; 6–20 scale), and rate pressure product (RPP) at fixed submaximal workloads following a 12-week RT intervention. Additionally, pre-and post-RT measures of brachial artery reactivity, an index of endothelial function, were obtained. METHODS: Fifteen low risk coronary patients (13 men, 2 women; mean ± SD age = 66.1 ± 5.1 yrs) completed a progressive 12-week RT program that complemented their regular aerobic training regimen. Prior to training, SBP, HR, RPP, and RPE were …

Translating Genetic And Preclinical Findings Into Autism Therapies, Maria Chahrour, Robin Kleiman, M Chiara Manzini

Pharmacology and Physiology Faculty Publications

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by social deficits and repetitive/restrictive interests. ASD is associated with multiple comorbidities, including intellectual disability, anxiety, and epilepsy. Evidence that ASD is highly heritable has spurred major efforts to unravel its genetics, revealing possible contributions from hundreds of genes through rare and common variation and through copy-number changes. In this perspective, we provide an overview of the current state of ASD genetics and of how genetic research has spurred the development of in vivo and in vitro models using animals and patient cells to evaluate the impact of genetic mutations …

Developmental Origins Of Health And Disease: Current Knowledge And Potential Mechanisms, Daniel J. Hoffman, Rebecca M. Reynolds, Daniel B. Hardy

Physiology and Pharmacology Publications

Epidemiologic and clinical research has provided a large body of evidence supporting the developmental origins of health and disease (DOHaD), but there has been a relative dearth of mechanistic studies in humans due to the complexity of working with large, longitudinal cohorts. Nonetheless, animal models of undernutrition have provided substantial evidence for the potential epigenetic, metabolic, and endocrine mechanisms behind DOHaD. Furthermore, recent research has explored the interaction between the environment and the gastrointestinal system by investigating how the gut microbial ecology may impact the capacity for nutrient processing and absorption in a manner that may limit growth. This review …

Endothelin-1 And Hypoxic Vascular Remodeling In Ovine Fetal Cerebral Arteries, Jinjutha Silpanisong

Loma Linda University Electronic Theses, Dissertations & Projects

Intrauterine hypoxia resulting from decreased maternal oxygen uptake, insufficient oxygen carrying capacity, or compromised oxygen delivery to the fetus jeopardizes fetal oxygen delivery, detrimentally affecting growth and development of the immature vasculature. Hypoxia transiently increases Hypoxia Inducible Factor-1α (HIF- 1α), which complexes with HIF-1β to form the active HIF-1 dimer that can affect transcription. This temporary rise in HIF-1 can promote gene transcription of ligands such as Vascular Endothelial Growth Factor (VEGF) and Endothelin-1 (ET-1), which rises and falls with HIF levels. The absence of chronic elevation of these ligands prompted the question of how long-term effects of hypoxia is …

Worked To Leisure: The Intersections Of Volunteerism, Work, And Leisure, Denise Nicole Cook

UNLV Theses, Dissertations, Professional Papers, and Capstones

Volunteerism and work are topics which academics in several disciplines research. This study is an examination of the intersection of work and volunteerism via the lens of role theory. According to role theorists, the term role refers to behaviors which are either a result of social position or expectations (Biddle 1986). Cognitive role theorists use vocabulary such as “role conflict” and “role overload” to identify incongruences sometimes found in roles individuals have in their lives (Biddle 1986). These incongruences are primarily examined as they relate to individual level consequences. This research explores volunteerism and work as they relate to role …

Dietary Intake And Energy Expenditure Of Pararescuemen During Routine Training, Andrea Woita

UNLV Theses, Dissertations, Professional Papers, and Capstones

Pararescuemen are one group of Air Force Special Operations Forces (SOF) who engage in vigorous physical training to achieve mission readiness. This type of training requires high energy expenditures and matching dietary intake to support basic physiological needs and to meet performance demands. However, few studies have investigated the energy expenditure and dietary intake of SOF and none have specifically examined these behaviors in Pararescuemen. The goal of this investigation was to determine the energy expenditure and dietary intake of Pararescuemen during routine training - a period when these operators receive supervision and guidance for performance improvements, recovery, and career …

Targeting Cancer Stem Cells In Recurrent Lung Cancer, Karen T. Udoh

Posters-at-the-Capitol

Lung cancer is the leading cause of cancer mortality in the world. Five-year survivability still remains dismal due to drug resistance. The development of drug resistance with cisplatin or platinum/taxane combination chemotherapies has led patients to suffer from recurrent lung cancer. These chemotherapy treatments target cancer cells but leave behind cancer stem cells. Cancer stem cells (CSCs) are stem-like tumor cells that have the potential to differentiate, self-renew, and proliferate. This allows the cancer to relapse even after initial elimination of the tumor. We hypothesize that Verrucarin J will inhibit cell proliferation in lung cancer cells and CSCs by inducing …

Disruption Of Hippocampal Multisynaptic Networks By General Anesthetics., Min-Ching Kuo, L Stan Leung

Physiology and Pharmacology Publications

BACKGROUND: Previous studies showed that synaptic transmission is affected by general anesthetics, but an anesthetic dose response in freely moving animals has not been done. The hippocampus provides a neural network for the evaluation of isoflurane and pentobarbital on multisynaptic transmission that is relevant to memory function.

METHODS: Male Long-Evans rats were implanted with multichannel and single electrodes in the hippocampus. Spontaneous local field potentials and evoked field potentials were recorded in freely behaving rats before (baseline) and after various doses of isoflurane (0.25 to 1.5%) and sodium pentobarbital (10 mg/kg intraperitoneal).

RESULTS: Monosynaptic population excitatory postsynaptic potentials at the …

Finasteride As A Model For Personalized Medicine, Ion G. Motofei, David L. Rowland, Ioana Păunică, Octavian C. Tănăsescu, Petrişor Banu, Stana Păunică

Journal of Mind and Medical Sciences

The side effects of Finasteride are currently a subject of controversy. Some studies report minor or acceptable adverse effects, which decrease after a variable period of time so that they do not necessitate terminating Finasteride administration. However, several clinical and neuro-endocrine studies show that some adverse effects persist indefinitely in the form of post-Finasteride syndrome, even after the drug cessation. This paper presents a possible explanation for these inconsistent findings. First, the study design of either informing or not informing patients prior therapy about possible adverse effects can influence the incidence and magnitude of reported adverse effects. Second, structural and …

Direct Antioxidant Properties Of Methotrexate: Inhibition Of Malondialdehyde-Acetaldehyde-Protein Adduct Formation And Superoxide Scavenging., Matthew C. Zimmerman, Dahn L. Clemens, Michael J. Duryee, Cleofes Sarmiento, Andrew Chiou, Carlos D. Hunter, Jun Tian, Lynell W. Klassen, James R. O'Dell, Geoffrey M. Thiele, Ted R. Mikuls, Daniel R. Anderson

Journal Articles: Cellular & Integrative Physiology

Methotrexate (MTX) is an immunosuppressant commonly used for the treatment of autoimmune diseases. Recent observations have shown that patients treated with MTX also exhibit a reduced risk for the development of cardiovascular disease (CVD). Although MTX reduces systemic inflammation and tissue damage, the mechanisms by which MTX exerts these beneficial effects are not entirely known. We have previously demonstrated that protein adducts formed by the interaction of malondialdehyde (MDA) and acetaldehyde (AA), known as MAA-protein adducts, are present in diseased tissues of individuals with rheumatoid arthritis (RA) or CVD. In previously reported studies, MAA-adducts were shown to be highly immunogenic, …

Peptidyl-Prolyl Isomerase 1 Regulates Ca(2+) Handling By Modulating Sarco(Endo)Plasmic Reticulum Calcium Atpase And Na(2+)/Ca(2+) Exchanger 1 Protein Levels And Function, V Sacchi, B Wang, D Kubli, A Martinez, J Jin, R Alvarez, N Hariharan, C Glembotski, T Uchida, J Malter, Y Yang, P Gross, C Zhang, S Houser, Marcello Rota, M Sussman

NYMC Faculty Publications

BACKGROUND: Aberrant Ca(2+) handling is a prominent feature of heart failure. Elucidation of the molecular mechanisms responsible for aberrant Ca(2+) handling is essential for the development of strategies to blunt pathological changes in calcium dynamics. The peptidyl-prolyl cis-trans isomerase peptidyl-prolyl isomerase 1 (Pin1) is a critical mediator of myocardial hypertrophy development and cardiac progenitor cell cycle. However, the influence of Pin1 on calcium cycling regulation has not been explored. On the basis of these findings, the aim of this study is to define Pin1 as a novel modulator of Ca(2+) handling, with implications for improving myocardial contractility and potential for …

Temporal Changes In Cortical And Hippocampal Expression Of Genes Important For Brain Glucose Metabolism Following Controlled Cortical Impact Injury In Mice, June Zhou, Mark Burns, Linda Huynh, Sonia Villapol, Daniel D. Taub, Juan M. Saavedra, Marc R. Blackman

Pharmacology and Physiology Faculty Publications

Traumatic brain injury (TBI) causes transient increases and subsequent decreases in brain glucose utilization. The underlying molecular pathways are orchestrated processes and poorly understood. In the current study, we determined temporal changes in cortical and hippocampal expression of genes important for brain glucose/lactate metabolism and the effect of a known neuroprotective drug telmisartan on the expression of these genes after experimental TBI. Adult male C57BL/6J mice (n = 6/group) underwent sham or unilateral controlled cortical impact (CCI) injury. Their ipsilateral and contralateral cortex and hippocampus were collected 6 h, 1, 3, 7, 14, 21, and 28 days after injury. …

A Protocol For The Administration Of Real-Time Fmri Neurofeedback Training, Matthew Sherwood, Emily E. Diller, Elizabeth Ey, Subhashini Ganapathy, Jeremy T. Nelson, Jason G. Parker

Neuroscience, Cell Biology & Physiology Faculty Publications

Neurologic disorders are characterized by abnormal cellular-, molecular-, and circuit-level functions in the brain. New methods to induce and control neuroplastic processes and correct abnormal function, or even shift functions from damaged tissue to physiologically healthy brain regions, hold the potential to dramatically improve overall health. Of the current neuroplastic interventions in development, neurofeedback training (NFT) from functional Magnetic Resonance Imaging (fMRI) has the advantages of being completely non-invasive, non-pharmacologic, and spatially localized to target brain regions, as well as having no known side effects. Furthermore, NFT techniques, initially developed using fMRI, can often be translated to exercises that can …