Effect of Natural Vs. Synthetic α-tocopherol on Neurogenesis-Related Genes in Cerebella of Juvenile α-tocopherol Transfer Protein-Null Mice

Abstract

Abstract Objectives Vitamin E (α-tocopherol, α-T) restriction during brain development alters the expression of neurogenesis-related genes in cerebella of juvenile α-tocopherol transfer protein-null (Ttpa−/−) mice. Synthetic α-T (SYN), compared to natural α-T (NAT), downregulates cerebellar myelin genes in adolescent Ttpa−/− mice. We studied how early-life exposure to SYN or NAT affects the expression of neurogenesis-related genes in juvenile Ttpa−/− mice. Methods Male and female Ttpa+/+ and Ttpa−/− mice were nursed by Ttpa+/−dams fed AIN-93G-based diets containing either SYN (∼816 mg α-T/kg diet) or NAT (∼600 mg α-T/kg diet). Homogenized brain tissues from 21 day old weanlings (n = 9/group) were used to measure total α-T concentrations via HPLC-PDA. The expression of genes critical for brain development (Rora, Shh), myelination (Plp1, Cntnap1, Mbp, Mobp, Nr1h3), and synaptic function (Cplx1, Necab1, Prkcg) were measured in the cerebellum via real-time qPCR. Results α-T concentrations were significantly lower in brains of Ttpa−/− mice (17.7 nmol/g) compared to Ttpa+/+ mice (37.5 nmol/g) (P < 0.001). Exposure to SYN vs. NAT resulted in similar total α-T brain levels within each genotype (Ttpa−/−: 19.8 vs. 15.6 nmol/g; Ttpa+/+: 42.5 vs. 32.6 nmol/g). Consistent with previous studies, Necab1 was significantly downregulated in Ttpa−/− mice (P < 0.05). The other selected neurogenesis-related genes were similarly expressed between all groups, regardless of genotype or dietary α-T source. Conclusions Brain α-T concentrations at weaning depended on the presence of Ttpa. α-T source did not modulate the selected neurogenesis genes, possibly because the natural and synthetic α-T diets each provided sufficient total α-T during development. Funding Sources Abbott Nutrition through the Center for Nutrition, Learning, and Memory (CNLM), Division of Nutritional Sciences Vision 20/20 Grant Program, and Division of Nutritional Sciences Margin of Excellence Research Program (all through the University of Illinois at Urbana-Champaign). KMR was supported by the AFRI NIFA Predoctoral Fellowships Grant Program (2019–67,011-29,514) from the U.S. Department of Agriculture, National Institute of Food and Agriculture.