title: Degeneration of mesencephalic dopaminergic neurons in klotho mouse related to vitamin D exposure.
abstract: Parkinson's disease (PD), which is characterized by degeneration of mesencephalic dopaminergic neurons of unclear etiology, is primarily an age-related neurodegenerative disorder, while the normal process of aging is also known to decrease the number of dopaminergic neurons in the substantia nigra pars compacta (SNc) and the ventral tegmental area (VTA). However, no consensus exists regarding how advancing age may predispose the dopaminergic system to PD. The Klotho-insufficient (klotho) mouse exhibits a syndrome that resembles human aging. Recent studies have revealed that abnormal activation of vitamin D is the major cause of this phenotype. In this study, we examined mesencephalic dopaminergic neurons of klotho mice and identified tyrosine hydroxylase-positive neurons in the SNc and VTA, and found that levels of striatal dopamine were significantly decreased with aging in klotho mice. Notably, these phenotypes were rescued by vitamin D restriction, suggesting that abnormal activation of vitamin D due to Klotho insufficiency leads to degeneration of the dopaminergic system. The present study provides new insights into the pathology of age-related degeneration of dopaminergic neurons possibly related to Klotho-mediated regulation of vitamin D.
authors.affiliation: Department of Neurology, Keio University School of Medicine, Japan.
authors.forename: Arifumi
authors.initials: A
authors.lastname: Kosakai
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ito
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Nihei
authors.forename: Shuji
authors.initials: S
authors.lastname: Yamashita
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Okada
authors.forename: Kazushi
authors.initials: K
authors.lastname: Takahashi
authors.forename: Norihiro
authors.initials: N
authors.lastname: Suzuki
mesh_terms: D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D004298:Dopamine / Q000378:metabolism; D005526:Food, Formulated; D005966:Glucuronidase / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D000090265:Klotho Proteins; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009410:Nerve Degeneration / Q000378:metabolism* / Q000473:pathology; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology; D013378:Substantia Nigra / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation / Q000502:physiology; D017557:Ventral Tegmental Area / Q000378:metabolism / Q000473:pathology; D014807:Vitamin D / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D014807:Vitamin D; D005966:Glucuronidase; D000090265:Klotho Proteins; D004298:Dopamine