Cortical gene expression in the vitamin E-deficient rat: possible mechanisms for the electrophysiological abnormalities of visual and neural function.
In mammals, severe and chronic deficiency of vitamin E (alpha-tocopherol) is associated with a characteristic neurological syndrome. Previously, we have shown that this syndrome is accompanied by electrophysiological abnormalities of neural and visual function. To investigate the molecular basis of the observed abnormalities, we used microarrays to monitor the expression of approximately 14,000 genes in the cerebral cortex from rats which had received diets containing 0, 1.25 and 5.0 mg/kg diet of all-rac-alpha-tocopheryl acetate for 14 months. Compared to the groups receiving 1.25 and 5.0 mg/kg alpha-tocopheryl acetate, a total of 11 genes were statistically significantly upregulated (> or =1.3-fold) and 34 downregulated (< or =1.3-fold) in the vitamin E-deficient group. Increased expression was observed for the genes encoding the antioxidant enzyme catalase and the axon guidance molecule tenascin-R, while decreased expression was detected for genes encoding protein components of myelin and determinants of neuronal signal propagation. Thus our observations suggest that vitamin E deficiency results in transcriptional alterations in the cerebral cortex of the rat which are consistent with the observed neurological and electrophysiological alterations.
Hyland
Stephen
S
DSM Nutritional Products, Research and Development, Kaiseraugst, Switzerland.
Muller
David
D
Hayton
Samantha
S
Stoecklin
Elisabeth
E
Barella
Luca
L
D000818:Animals; D002374:Catalase / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism / Q000503:physiopathology*; D020869:Gene Expression Profiling; D008297:Male; D009422:Nervous System Diseases / Q000209:etiology / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D017208:Rats, Wistar; D014158:Transcription, Genetic; D014786:Vision Disorders / Q000209:etiology / Q000378:metabolism; D014811:Vitamin E Deficiency / Q000150:complications*; D014815:Vitamins / Q000008:administration & dosage*; D024502:alpha-Tocopherol / Q000008:administration & dosage*
D014815:Vitamins; D002374:Catalase; D024502:alpha-Tocopherol