This Article Free Full Text Free Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Valentine, W. M. Articles by Burk, R. F. Search for Related Content PubMed PubMed Citation Articles by Valentine, W. M. Articles by Burk, R. F. Social Bookmarking                         What's this?

Brainstem Axonal Degeneration in Mice with Deletion of Selenoprotein P

¹ Department of Pathology
² Division of Gastroenterology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee
³ Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, Tennessee

Correspondence: Address correspondence to: William M. Valentine, Department of Pathology, C3320 MCN, Vanderbilt University Medical Center, Nashville, TN 37232-2561, USA; e-mail:bill.valentine{at}vanderbilt.edu

Selenoprotein P is an abundant extracellular protein that is expressed in liver, brain, and other tissues. Studies in mice with the selenoprotein P gene deleted (Sepp^–/– mice) have implicated the protein in maintaining brain selenium. Sepp^–/– mice fed a normal or low selenium diet develop severe motor impairment and die, but Sepp^–/– mice fed a high selenium diet remain clinically unimpaired. As an initial step to evaluate the effect of selenoprotein P deletion on central nervous system architecture, the brains and cervical spinal cords of Sepp^–/– and Sepp^+/+ mice fed low or high selenium diets were examined by light and electron microscopy. Brains of Sepp^–/– mice demonstrated no gross abnormalities. At the light microscopic level, however, Sepp^–/– mice fed either the selenium deficient diet or the high selenium diet had enlarged dystrophic axons and degenerated axons in their brainstems and cervical spinal cords. No axonal lesions were observed in the Sepp^+/+ mice fed either diet. Electron microscopy demonstrated that the enlarged axons in the Sepp^–/– mice were packed with organelles, suggesting a deficit in fast axonal transport. The similar severity of axonal lesions observed in Sepp^–/– mice fed the 2 diets suggests that axonal dystrophy is a common phenotype for deletion of selenoprotein P regardless of selenium intake and that additional studies will be required to determine the pathogenesis of the neurological signs and mortality observed in Sepp^–/–mice fed a low selenium diet.

Key Words: Axonal degeneration • axonal dystrophy • axonal transport • selenium deficiency • selenoprotein P • spasticity

Abbreviations: Sepp^–/– mice, selenoprotein P gene-deleted mice • Sepp^+/+ mice, wild-type mice

Toxicologic Pathology, Vol. 33, No. 5, 570-576 (2005)
DOI: 10.1080/01926230500243045


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?