title: Rice Bran Dietary Supplementation Improves Neurological Symptoms and Loss of Purkinje Cells in Vitamin E-Deficient Mice.
abstract: BACKGROUND
  Vitamin E (VE, α-tocopherol) is a fat-soluble vitamin and is well known as an antioxidant. A deficiency in VE induces oxidative stress in the brain and causes motor and memory dysfunction. The consumption of a VE-rich diet has been given much attention in recent years, in regards to anti-aging and the prevention of age-related neuronal disorders.
  
  
  METHODS
  A VE-deficient mouse model was prepared by feeding the animals a diet lacking VE. In addition, to evaluate the effect of VE-containing rice bran (RB) on VE deficiency, a diet including RB was also provided. VE levels in the brain tissue, as well as in the RB, were measured using an HPLC system. Behavioral tests, including rotarod, wheel running activity, Y-maze, and elevated plus maze were performed. To clarify the effect of VE deficiency and RB, we investigated the induction of heme oxygenase-1 (HO-1). Histological studies were performed using HE staining and immunohistochemical studies were performed using antibodies against glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule 1 (Iba1).
  
  
  RESULTS
  VE in the mouse brain under a VE-deficient diet was decreased, and recovered α-tocopherol levels were observed in the brain of mice fed an RB diet. Motor behavioral scores were decreased in VE-deficient conditions, while the supplementation of RB improved motor function. HO-1, a marker of oxidative stress, was upregulated in the mouse brain under VE deficiency, however, RB supplementation inhibited the increase of HO-1. Histological analyses showed neuronal degeneration of Purkinje cells and decreased GFAP-immunoreactivity of Bergmann glia in the cerebellum. In addition, activated astrocytes and microglia were observed in mice fed the VE-deficient diet. Mice fed the RB diet showed improvement in these histological abnormalities.
  
  
  CONCLUSIONS
  A VE-deficient diet induced motor dysfunction in mice due to the degeneration of Purkinje cells in the cerebellum. Oral supplementation of RB increases VE in the brain and improved the motor dysfunction caused by VE deficiency. Thus, RB or unpolished rice may be a promising VE supplement.
authors.affiliation: Division of Medical Biochemistry, Department of Pathophysiological and Therapeutic Science, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8503, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Division of Medical Biochemistry, Department of Pathophysiological and Therapeutic Science, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8503, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nakaso
authors.affiliation: Division of Medical Biochemistry, Department of Pathophysiological and Therapeutic Science, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8503, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Horikoshi
authors.affiliation: Division of Medical Biochemistry, Department of Pathophysiological and Therapeutic Science, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8503, Japan; †Division of Surgical Oncology, Department of Surgery, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8503, Japan.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Hanaki
authors.affiliation: Division of Medical Biochemistry, Department of Pathophysiological and Therapeutic Science, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8503, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Yamakawa
authors.affiliation: ‡Division of Anesthesiology and Clinical Care Medicine, Department of Surgery, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8503, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Nakasone
authors.affiliation: ‡Division of Anesthesiology and Clinical Care Medicine, Department of Surgery, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8503, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Kitagawa
authors.affiliation: §Planning & Development Department, Eisai Food & Chemical Co., Ltd., Tokyo 103-0027, Japan.
authors.forename: Taisuke
authors.initials: T
authors.lastname: Koike
authors.affiliation: Division of Medical Biochemistry, Department of Pathophysiological and Therapeutic Science, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8503, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Matsura
keywords: Bergmann glia; antioxidant; oxidative stress; rice bran; vitamin E