Neuronal Expression of Hemoglobin in Multiple Sclerosis Cortex

Summary

Principal Investigator: Jennifer McDonough
Abstract: DESCRIPTION (provided by applicant): Damage to and loss of neurons and axons is correlated with disability in multiple sclerosis (MS), thus neuroprotective therapies are urgently needed. In previous studies we have found altered expression of mitochondrial genes and proteins involved in respiration resulting in dysfunctional mitochondrial activity in postmortem MS cortex. Recently, we have shown that hemoglobin is upregulated in MS cortex and have localized hemoglobin expression to neurons in the MS brain. We have also found hemoglobin expression in primary cultures of neurons isolated from rat brain. This is a surprising and novel finding and provides support for our hypothesis that hemoglobin expression may be involved in neuronal respiration. The goal of this study is to understand the function of hemoglobin expression in neurons and its significance to neuropathology in MS. In the proposed study we will investigate the extent and localization of hemoglobin expression in different regions of the MS brain by in situ hybridization, RT-PCR, western blotting, confocal imaging, and electron microscopy of postmortem MS and control tissue. We will investigate the mechanisms which regulate hemoglobin expression in primary neuronal cultures and will assess the role of hemoglobin in neuronal respiration and oxidative phosphorylation by performing high resolution respirometry on neuroblastoma cells expressing hemoglobin subunits from a mammalian expression vector, and on brain slices from mice treated with erythropoietin which increases hemoglobin expression in the brain. We will also investigate the possibility that hemoglobin serves a neuroprotective role in the brain as a scavenger of free radicals.
Funding Period: 2012-09-15 - 2014-08-31
more information: NIH RePORT

Research Grants

Detail Information

Research Grants32

  1. CENTER FOR GASTROINTESTINAL BIOLOGY AND DISEASE
    Robert S Sandler; Fiscal Year: 2013
    ..Through all of its activities, the Center improves communication, promotes collaboration, develops careers and generally enriches the intellectual climate for digestive disease research. ..
  2. Thrombus Formation and Antithrombotic Intervention
    John H Griffin; Fiscal Year: 2013
    ..New knowledge will contribute to improving prevention, diagnosis and treatment of relevant diseases related to thrombosis. ..
  3. Mitochondrial Proteins in Parkinson's Disease
    J Timothy Greenamyre; Fiscal Year: 2013
    ....
  4. Host Factors in Regulation of Inflammatory and Fibroproliferative Lung Disease
    PAUL WESLEY NOBLE; Fiscal Year: 2013
    ..Each of these projects shares the common theme that interactions of host factors regulates inflammatory and fibrotic lung diseases. ..
  5. CENTER FOR BIOMEDICAL RESEARCH
    Timothy Turner; Fiscal Year: 2013
    ..abstract_text> ..
  6. Intellectual and Development Disabilities Research Center
    Marc Yudkoff; Fiscal Year: 2013
    ..5 million from NICHD). The Center includes an excess of 70 Penn faculty at 15 departments at the Schools of Medicine, Veterinary Medicine, Nursing, the Wistar Institute, and the College of Arts and Sciences. ..
  7. Center for Novel Therapeutics for HIV-Associated Cognitive Disorders
    Justin C McArthur; Fiscal Year: 2013
    ..5. To identify and validate surrogate biomarkers based on proteomics and lipomics. ..
  8. Spatial and Temporal Scales of Motor Sequence Learning
    SCOTT THOMAS GRAFTON; Fiscal Year: 2013
    ..The collaborative effort can be expected to significantly advance our knowledge about mechanisms that support motor cortex plasticity. ..
  9. CARDIAC ENERGY METABOLISM IN HEART FAILURE
    Hani N Sabbah; Fiscal Year: 2013
    ..In addition, there will be four Cores (Administrative, Large Animal/Histology, Metabolism, and Mitochondria/Mass Spec). ..
  10. Molecular Regulation of Cell Development and Differentiation
    Dale R Abrahamson; Fiscal Year: 2013
    ..abstract_text> ..
  11. Regulation of CNS viral persistence
    Cornelia Bergmann; Fiscal Year: 2013
    ..Importantly, it will provide valuable information on the interactions of specific CNS cells involved in viral persistence and demyelination and the cellular and soluble mediators of the host immune response...
  12. COBRE for Skeletal Health and Repair
    Qian Chen; Fiscal Year: 2013
    ..This multidisciplinary approach is absolutely necessary to develop translational strategies for prevention and treatment of skeletal joint diseases. ..
  13. Injury and Recovery in Developing Brain
    Flora M Vaccarino; Fiscal Year: 2013
    ..The long-term goal of these studies is to identify new means of therapeutic intervention to decrease the developmental disability and neurobehavioral sequelae of preterm birth. ..
  14. Iron in the pathogenesis of Friedreich's ataxia
    ARNULF HANS WERNER KOEPPEN; Fiscal Year: 2013
    ..The work is clinically relevant because it will resolve questions about iron in the formal pathogenesis and natural history of FRDA, and the potential value of iron chelation. ..
  15. Combined Therapy for Intracerebral Hemorrhage Treatment
    Kenneth R Wagner; Fiscal Year: 2013
    ..Furthermore, these studies should provide a better understanding of the early and delayed mechanisms underlying brain injury from ICH. ..
  16. Tissue injury and inflammation in MS (P50)
    Bruce D Trapp; Fiscal Year: 2013
    ..abstract_text> ..
  17. Signaling Processes Underlying Cardiovascular Function
    Jeffrey Robbins; Fiscal Year: 2013
    ..These projects are supported by 3 Cores: Core A: The Administrative Core;Core B: The Physiology Core and Core C: The Imaging-Cell Culture Core. (End of Abstract) ..
  18. Expanding the National Health Accounts
    David M Cutler; Fiscal Year: 2013
    ..Establishment of a set of national health accounts will allow us as a society to understand which medical interventions improve the health of the U.S. population most efficiently. ..
  19. DEGENERATIVE AND DEMENTING DISEASES OF AGING
    Stanley B Prusiner; Fiscal Year: 2013
    ..The ultimate goal of all the proposed studies is to define the molecular events that feature in the formation of human prions in order to develop therapeutics that cure the human prion diseases. ..
  20. Molecular Mechanisms linking Aging, Abeta Proteotoxicity and Neurodegeneration
    Jeffery W Kelly; Fiscal Year: 2013
    ..abstract_text> ..
  21. INITIATION OF HUMAN LABOR: PREVENTION OF PREMATURITY
    Carole R Mendelson; Fiscal Year: 2013
    ..We propose that these interrelated projects, carried out by a highly interactive research team, will achieve the long-range goals of this Program and contribute to a reduction in the incidence of preterm birth. ..
  22. MITOCHONDRIAL ENCEPHALOMYOPATHIES AND MENTAL RETARDATION
    Salvatore DiMauro; Fiscal Year: 2013
    ....
  23. EARLY EVENTS IN ALZHEIMER PATHOGENESIS
    SUE TILTON GRIFFIN; Fiscal Year: 2013
    ..The synergy between our aims, approaches, and measures will enable us to meet our goal of defining early cellular interactions toward development of rational interventions in AD. ..
  24. Structural bases of the functions of RNA-protein machines
    THOMAS ARTHUR STEITZ; Fiscal Year: 2013
    ..Also of interest will be the ways in which the structures and properties of RNA molecules can be utilized to carry out various biological functions often analogous to those performed by proteins. ..
  25. Role of Parkin in Familial and Idiopathic Parkinson's Disease
    Matthew J LaVoie; Fiscal Year: 2013
    ..This work will elucidate novel biochemical pathways involved in the pathogenesis of PD and potentially uncover innovative targets for therapeutic intervention. ..
  26. Emory Alzheimer's Disease Center
    Allan I Levey; Fiscal Year: 2013
    ..abstract_text> ..