Synthetic α-Tocopherol, Compared with Natural α-Tocopherol, Downregulates Myelin Genes in Cerebella of Adolescent Ttpa-null Mice

Vitamin E (α-tocopherol; αα-T) deficiency causes spinocerebellar ataxia. α-T supplementation improves neurological symptoms, but little is known about the differential bioactivities of natural versus synthetic α-T during early life. We assessed the effects of dietary α-T dose and source on tissue α-...

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Bibliographic Details
Published in:The Journal of nutrition 2020-05, Vol.150 (5), p.1031-1040
Main Authors: Ranard, Katherine M, Kuchan, Matthew J, Bruno, Richard S, Juraska, Janice M, Erdman, John W
Format: Article
Language:English
Subjects:
Abnormalities
adolescent
Adolescents
all-rac α-tocopherol
alpha-Tocopherol - chemical synthesis
alpha-Tocopherol - pharmacology
Animal Feed - analysis
Animals
Ataxia
Bioaccumulation
Body Weight
brain
Carrier Proteins - genetics
Carrier Proteins - metabolism
Cerebellum
Cerebellum - drug effects
Cerebellum - metabolism
Cerebral cortex
Diet
Dietary supplements
Dosage
Eating
Effects
Gene expression
Gene Expression Regulation - drug effects
Gene sequencing
Genes
Male
Mice
Mice, Knockout
Myelin
Myelin Sheath - metabolism
Nutrient deficiency
Ribonucleic acid
RNA
RNA-sequencing
RRR α-tocopherol
Sox10 protein
Stereoisomers
Teenagers
Tocopherol
Transcription factors
Ttpa-null mouse
Vitamin E
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Summary:Vitamin E (α-tocopherol; αα-T) deficiency causes spinocerebellar ataxia. α-T supplementation improves neurological symptoms, but little is known about the differential bioactivities of natural versus synthetic α-T during early life. We assessed the effects of dietary α-T dose and source on tissue α-T accumulation and gene expression in adolescent α-Tocopherol transfer protein-null (Ttpa–/–) mice. Three-week-old male Ttpa–/– mice (n = 7/group) were fed 1 of 4 AIN-93Gbased diets for 4 wk: vitamin Edeficient (VED; below α-T limit of detection); natural α-T, 600 mg/kg diet (NAT); synthetic α-T, 816 mg/kg diet (SYN); orhigh synthetic α-T, 1200 mg/kg diet (HSYN). Male Ttpa+/+ littermates fed AIN-93G [75 mg synthetic α-T (CON)] servedas controls (n = 7). At 7 wk of age, tissue α-T concentrations and stereoisomer profiles were measured for all groups. Ttpa–/– mice fed VED had undetectable brain α-T concentrations. Cerebral cortex α-T concentrations weregreater in Ttpa–/– mice fed NAT (9.1 ± 0.7 nmol/g), SYN (10.8 ± 1.0 nmol/g), and HSYN (13.9 ± 1.6 nmol/g) compared withthe VED group but were significantly lower than in Ttpa+/+ mice fed CON (24.6 ± 1.2 nmol/g) (P < 0.001). RRR-α-T wasthe predominant stereoisomer in brains of Ttpa+/+ mice (~40%) and Ttpa–/– mice fed NAT (~94%). α-T stereoisomercomposition was similar in brains of Ttpa–/– mice fed SYN and HSYN (2R: ~53%; 2S: ~47%). Very few of the 16,774genes measured were differentially expressed. However, compared with the NAT diet, HSYN significantly downregulated20 myelin genes, including 2 transcription factors: SRY-box transcription factor 10 (Sox10) and myelin regulatory factor(Myrf), and several downstream target genes (false discovery rate
ISSN:0022-3166
1541-6100
DOI:10.1093/jn/nxz330