Skip directly to search Skip directly to A to Z list Skip directly to page options Skip directly to site content

NIOSHTIC-2 Publications Search

Search Results

Vacuolar leukoencephalopathy with widespread astrogliosis in mice lacking transcription factor Nrf2.

Authors
Hubbs-AF; Benkovic-SA; Miller-DB; O'Callaghan-JP; Battelli-L; Schwegler-Berry-D; Ma-Q
Source
Am J Pathol 2007 Jun; 170(6):2068-2076
NIOSHTIC No.
20032325
Abstract
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.
Keywords
Analytical-processes; Age-factors; Animal-studies; Nerve-damage; Nerve-function; Neurophysiology; Physiological-effects; Physiological-factors; Physiological-response; Brain-function; Immune-reaction; Immune-system
Contact
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
CODEN
AJPAA4
Publication Date
20070601
Document Type
Journal Article
Email Address
qam1@cdc.gov
Fiscal Year
2007
NTIS Accession No.
NTIS Price
Issue of Publication
6
ISSN
0002-9440
NIOSH Division
HELD
Priority Area
Manufacturing
Source Name
American Journal of Pathology
State
WV
TOP