title: Combined vitamin C and E deficiency induces motor defects in gulo(-/-)/SVCT2(+/-) mice.
abstract: OBJECTIVE
  Key antioxidants, vitamins C and E, are necessary for normal brain development and neuronal function. In this study, we depleted both of these vitamins in two mouse models to determine if oxidative stress due to combined vitamin C and E dietary deficiency altered their neurological phenotype. The first model lacked both alleles for the Gulonolactone oxidase gene (Gulo(-/-)) and therefore was unable synthesize vitamin C. To obtain an additional cellular deficiency of vitamin C, the second model also lacked one allele for the cellular vitamin C transporter gene (Gulo(-/-)/SVCT2(+/-)).
  
  
  METHODS
  The experimental treatment was 16 weeks of vitamin E deprivation followed by 3 weeks of vitamin C deprivation. Mice were assessed for motor coordination deficits, vitamin levels, and oxidative stress biomarkers.
  
  
  RESULTS
  In the first model, defects in motor performance were more apparent in both vitamin C-deficient groups (VE+VC-, VE-VC-) compared to vitamin C-supplemented groups (VE+VC+, VE-VC+) regardless of vitamin E level. Analysis of brain cortex and liver confirmed decreases of at least 80% for each vitamin in mice on deficient diets. Vitamin E deficiency doubled oxidative stress biomarkers (F2-isoprostanes and malondialdehyde). In the second model, Gulo(-/-)/SVCT2(+/-) mice on the doubly deficient diets showed deficits in locomotor activity, Rota-rod performance, and other motor tasks, with no concomitant change in anxiety or spatial memory.
  
  
  CONCLUSIONS
  Vitamin E deficiency alone caused a modest oxidative stress in brain that did not affect motor performance. Adding a cellular deficit in vitamin C to dietary deprivation of both vitamins significantly impaired motor performance.
authors: Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232-0465, USA. Marquicia.r.pierce@vanderbilt.edu
authors: Marquicia R
authors: MR
authors: Pierce
authors: Danielle L
authors: DL
authors: Diasio
authors: Laurisa M
authors: LM
authors: Rodrigues
authors: Fiona E
authors: FE
authors: Harrison
authors: James M
authors: JM
authors: May
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage; D001205:Ascorbic Acid / Q000008:administration & dosage* / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D019587:Dietary Supplements; D004195:Disease Models, Animal; D028441:F2-Isoprostanes / Q000097:blood; D005260:Female; D050544:L-Gulonolactone Oxidase / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D051379:Mice; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects*; D014808:Vitamin D Deficiency / Q000150:complications / Q000473:pathology*; D014810:Vitamin E / Q000008:administration & dosage* / Q000097:blood; D014811:Vitamin E Deficiency / Q000150:complications / Q000473:pathology*
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D028441:F2-Isoprostanes; D014810:Vitamin E; D008315:Malondialdehyde; D050544:L-Gulonolactone Oxidase; D001205:Ascorbic Acid