Vacuolar Leukoencephalopathy with Widespread Astrogliosis in Mice Lacking Transcription Factor Nrf2

Details

• Personal Author:
  Battelli L ; Benkovic SA ; Hubbs, Ann F. ; Ma Q ; Miller DB ; O'Callaghan JP ; Schwegler-Berry D
• Description:
  NFE2-related factor 2 (Nrf2), an oxidant-activated CNC bZip transcription factor, has been implicated in defense against oxidative stress and chemical insults in a range of cell and tissue types, including the central nervous system. Here, we report that deletion of the Nrf2 gene in mice caused vacuolar (spongiform) leukoencephalopathy with widespread astrogliosis. The leukoencephalopathy was present in all Nrf2-null mice more than 10 months of age, was characterized by vacuolar degeneration involving all major brain regions, and was most apparent in the white tracts of the cerebellum and pons. Vacuolar degeneration in white tracts was attributable to myelin unwinding and intramyelinic cysts, and double-label immunofluorescence for 4-hydroxy-2-nonenal and myelin basic protein localized free-radical-induced oxidative damage to the myelin sheath. Moreover, the brains of Nrf2-null mice exhibited widespread astrocyte activation with profusion of glial fibrillary acidic protein-immunoreactive glial processes. The study uncovered a possible physiological role for Nrf2 in maintaining central nervous system myelin. If this role is confirmed, it may suggest new approaches to treating genetically and chemically induced myelin degenerative diseases. [Description provided by NIOSH]
• Subjects:
  Age Factors Animals Immune System Nervous System Occupational Health Safety
• Keywords:
  Age-factors Analytical-processes Animal-studies Brain-function Immune-reaction Immune-system Nerve-damage Nerve-function Neurophysiology Physiological-effects Physiological-factors Physiological-response

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• ISSN:
  0002-9440
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  170
• Issue:
  6
• NIOSHTIC Number:
  nn:20032325
• Citation:
  Am J Pathol 2007 Jun; 170(6):2068-2076
• Contact Point Address:
  Qiang Ma, Receptor Biology Laboratory, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, 1095 Willowdale Rd., Morgantown, WV 26505
• Email:
  qam1@cdc.gov
• Federal Fiscal Year:
  2007
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  The American Journal of Pathology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:4ca3e3c439467313804b2d736a3dca00febc946844320678ed53eb98c382f0f2463970b76e88f23ff706caac3126fa18418819af82da1a9f1e968e0c793315df
• Download URL:
  https://stacks.cdc.gov/view/cdc/186346/cdc_186346_DS1.pdf
• File Type:
  [PDF - 1.09 MB ]