Neurodegeneration in mice resulting from loss of functional selenoprotein P or its receptor apolipoprotein E receptor 2.

Valentine WM, Abel TW, Hill KE, Austin LM, Burk RF
J Neuropathol Exp Neurol. 2008 67 (1): 68-77

PMID: 18172410 · DOI:10.1097/NEN.0b013e318160f347

Selenoprotein P (Sepp1) is involved in selenium homeostasis. Mice with a deletion of Sepp1, replacement of it by the shortened form Sepp1(Delta240-361), or deletion of its receptor apolipoprotein E receptor 2 develop severe neurologic dysfunction when fed low-selenium diet. Because the brainstems of Sepp1(-/-) mice had been observed to contain degenerated axons, a study of these 3 strains was made under selenium-deficient and high-selenium (control) conditions. Selenium-deficient wild-type mice were additional controls. Serial sections of the brain were evaluated with amino cupric silver degeneration and anti-glial fibrillary acidic protein stains. All 3 strains with altered Sepp1 metabolism developed severe axonal injury when fed selenium deficient diet. This injury was mitigated by high-selenium diet and was absent from selenium-deficient wild-type mice. Injury was most severe in Sepp1(-/-) mice, with staining in at least 6 brain regions. Injury in Sepp1(Delta240-361) and apolipoprotein E receptor 2 mice was less severe and occurred only in areas injured in Sepp1(-/-) mice, suggesting a common selenium-related etiology. Affected brain regions were primarily associated with auditory and motor functions, consistent with the clinical signs. Those areas have high metabolic rates. We conclude that interference with Sepp1 function damages auditory and motor areas, at least in part by restricting selenium supply to the brain regions.

MeSH Terms (13)

Animals Brain Gene Deletion Glial Fibrillary Acidic Protein Imaging, Three-Dimensional LDL-Receptor Related Proteins Mice Mice, Inbred C57BL Mice, Knockout Nerve Degeneration Receptors, Lipoprotein Selenoprotein P Silver Staining

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