title: Estrogen receptor-mediated effect of δ-tocotrienol prevents neurotoxicity and motor deficit in the MPTP mouse model of Parkinson's disease.
abstract: Neuroprotection following signal transduction has been investigated recently as a strategy for Parkinson's disease (PD) therapy. While oxidative stress is important in the pathogenesis of PD, neuroprotection using antioxidants such as α-tocopherol have not been successful. δ-tocotrienol (δT3), a member of the vitamin E family, has received attention because of activities other than its antioxidative effects. In the present study, we examined the estrogen receptor-β (ERβ)-mediated neuroprotective effects of δT3 in a mouse model of PD. ERβ is expressed in neuronal cells, including dopaminergic neurons in the substantia nigra. Daily forced oral administration of δT3 inhibited the loss of dopaminergic neurons in the substantia nigra. In addition, the ER inhibitor tamoxifen canceled the neuroprotective effects of δT3. Moreover, δT3 administration improved the performance of the PD mice in the wheel running activity, while tamoxifen inhibited this improved performance. These results suggest that the oral administration of δT3 may be useful in the treatment of PD patients, and ERβ may be a candidate target for the neuroprotection activity of δT3.
authors.affiliation: Division of Medical Biochemistry, Department of Pathophysiological and Therapeutic Science, Tottori University Faculty of Medicine, Japan. Electronic address: kazuhiro@med.tottori-u.ac.jp.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nakaso
authors.affiliation: Division of Medical Biochemistry, Department of Pathophysiological and Therapeutic Science, Tottori University Faculty of Medicine, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Horikoshi
authors.affiliation: Division of Medical Biochemistry, Department of Pathophysiological and Therapeutic Science, Tottori University Faculty of Medicine, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Division of Medical Biochemistry, Department of Pathophysiological and Therapeutic Science, Tottori University Faculty of Medicine, Japan; Division of Surgical Oncology, Department of Surgery, Tottori University Faculty of Medicine, Japan.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Hanaki
authors.affiliation: Division of Anesthesiology and Clinical Care Medicine, Department of Surgery, Tottori University Faculty of Medicine, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Nakasone
authors.affiliation: Division of Anesthesiology and Clinical Care Medicine, Department of Surgery, Tottori University Faculty of Medicine, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Kitagawa
authors.affiliation: Planning & Development Department, Eisai Food & Chemical Co., Ltd., Japan.
authors.forename: Taisuke
authors.initials: T
authors.lastname: Koike
authors.affiliation: Division of Medical Biochemistry, Department of Pathophysiological and Therapeutic Science, Tottori University Faculty of Medicine, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Matsura
mesh_terms: D015655:1-Methyl-4-phenylpyridinium; D000818:Animals; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism*; D005260:Female; D008297:Male; D008810:Mice, Inbred C57BL; D009048:Motor Skills; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D018696:Neuroprotective Agents; D014810:Vitamin E; C082097:tocotrienol, delta; D015655:1-Methyl-4-phenylpyridinium
keywords: Estrogen receptor; MPTP; Parkinson's disease; Tocotrienol; Vitamin E