Natural and Synthetic [alpha] -Tocopherol Modulate the Neuroinflammatory Response in the Spinal Cord of Adult Ttpa-null Mice

• Published in: Current developments in nutrition Vol. 5; no. 3; p. 1
• Main Authors: Ranard, Katherine M, Kuchan, Matthew J, Juraska, Janice M, Erdman, John W, Jr
• Format: Journal Article
• Language: English
• Published: Oxford University Press 01.03.2021
• Subjects: Alpha tocopherol; Care and treatment; Health aspects; Inflammation; Nervous system diseases; Spinal cord; United States
• ISSN: 2475-2991; 2475-2991

Background: Vitamin E ([alpha]-tocopherol, [alpha]-T) deficiency causes neurological pathologies. [alpha]-T supplementation improves outcomes, but the relative bioactivities of dietary natural and synthetic [alpha]-T in neural tissues are unknown. Objective: The aim was to assess the effects of dietary [alpha]-T source and dose on oxidative stress and myelination in adult [alpha]-tocopherol transfer protein-null ([Ttpa.sup.-/-]) mouse cerebellum and spinal cord. Methods: Three-week-old male [Ttpa.sup.-/-] mice (n = 56) were fed 1 of 4 AIN-93G-based diets for 37 wk: vitamin E-deficient (VED; below [alpha]-T limit of detection); natural [alpha]-T, 600 mg/kg diet (NAT); synthetic [alpha]-T, 816 mg/kg diet (SYN); or high synthetic [alpha]-T, 1200 mg/kg diet (HSYN). Male [Ttpa.sup.+/+] littermates (n = 14) fed AIN-93G (75 mg synthetic [alpha]-T/kg diet; CON) served as controls. At 40 wk of age, total and stereoisomer [alpha]-T concentrations and oxidative stress markers were determined (n = 7/group). Cerebellar Purkinje neuron morphology and white matter areas in cerebellum and spinal cord were assessed in a second subset of animals (n = 7/group). Results: Cerebral cortex [alpha]-T concentrations were undetectable in [Ttpa.sup.-/-] mice fed the VED diet. [alpha]-T concentrations were increased in NAT (4.6 [+ or -] 0.3 nmol/g), SYN (8.0 [+ or -] 0.7 nmol/g), and HSYN (8.5 [+ or -] 0.3 nmol/g) mice, but were significantly lower than in [Ttpa.sup.+/+] mice fed CON (27.8 [+ or -] 1.9 nmol/g) (P < 0.001). 2R stereoisomers constituted the majority of [alpha]-T in brains of [Ttpa.sup.+/+] mice (91%) and [Ttpa.sup.-/-] mice fed NAT (100%), but were substantially lower in the SYN and HSYN groups (~53%). Neuroinflammatory genes were increased in the spinal cord, but not cerebellum, of VED-fed animals; NAT, SYN, and HSYN normalized their expression. Cerebellar Purkinje neuron atrophy and myelin pathologies were not visible in [Ttpa.sup.-/-] mice. Conclusions: Natural and synthetic [alpha]-T supplementation normalized neuro-inflammatory markers in neural tissues of 10-mo-old [Ttpa.sup.-/-] mice. [alpha]-T prevents tissue-specific molecular abnormalities, which may prevent severe morphological changes during late adulthood. Curr Dev Nutr 2021;5:nzab008. Keywords: vitamin E, RRR-[alpha]-tocopherol, all-rac-[alpha]-tocopherol, central nervous system, oxidative stress, Ttpa-null mouse