Cortical Gene Expression in the Vitamin E-Deficient Rat: Possible Mechanisms for the Electrophysiological Abnormalities of Visual and Neural Function

Abstract

In mammals, severe and chronic deficiency of vitamin E (α-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 ∼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-α-tocopheryl acetate for 14 months. Compared to the groups receiving 1.25 and 5.0 mg/kg α-tocopheryl acetate, a total of 11 genes were statistically significantly upregulated (≧1.3-fold) and 34 downregulated (≤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.

Mice lacking α-tocopherol transfer protein gene have severe α-tocopherol deficiency in multiple regions of the central nervous system

“…Genome-wide mRNA expression analysis of the cerebral cortex from young, asymptomatic α-TTP-KO mice suggest a role for α-T in myelination and synaptic functions in the CNS (Gohil et al, 2004;Gohil et al, 2003). Similar observations were reported in rats fed α-T deficient diets (Hyland et al, 2006). The data from these gene profiling studies appear to provide a molecular basis for the histological and morphometric observations documented in earlier investigations.…”

Altered vitamin E status in Niemann-Pick type C disease

“…We attributed this decrease to the severe hypomyelination of the cortex that accompanies NPC disease ( 28,41,72 ). Both cholesterol and tocopherol are important constituents of myelin (73)(74)(75), and vitamin E defi ciency causes hypomyelination (76)(77)(78). In the cerebellum, the only statistically signifi cant difference was observed in 12-week-old Npc2 Ϫ / Ϫ mice, which exhibited a ‫ف‬ 30% increase in the content of tocopherol as well as cholesterol, compared with wild-type animals ( Fig.…”

Tocopherol transfer protein deficiency modifies nuclear receptor transcriptional networks in lungs: Modulation by cigarette smoke in vivo

“…The transcriptional response to chronic dietary AT deficiency also affects the transcriptomes of the cerebral cortex (Hyland et al, 2006) and the hippocampus (Rota et al, 2005). Dietary AT-deficiency for 14 months in male rats resulted in the repression of 34 genes that included genes encoding myelin proteins and those for neuronal signal propagation, suggesting molecular targets that may account for neurological and electrophysiological alterations (Hyland et al, 2006).…”