TY - JOUR
T1 - Degeneration of mesencephalic dopaminergic neurons in klotho mouse related to vitamin D exposure
AU - Kosakai, Arifumi
AU - Ito, Daisuke
AU - Nihei, Yoshihiro
AU - Yamashita, Shuji
AU - Okada, Yasunori
AU - Takahashi, Kazushi
AU - Suzuki, Norihiro
N1 - Funding Information:
We are grateful to Mr. Satoshi Kusakari, Mr. Hitoshi Abe, Ms. Yuko, Hashimoto, Ms. Minako Suzuki, Ms. Kiyora Nakajima, and Mr. Kazuo Suzuki (Department of Pathology, Keio University School of Medicine) for preparation of paraffin sections. This work was supported by Eisai Co., Ltd. , and the Ministry of Education, Culture, Sports, Science, and Technology of Japan (No. 18590955 ).
PY - 2011/3/25
Y1 - 2011/3/25
N2 - 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.
AB - 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.
KW - Aging
KW - Dopamine
KW - Dopaminergic neuron
KW - Klotho
KW - Neurodegeneration
KW - Parkinson's disease
KW - Vitamin D
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U2 - 10.1016/j.brainres.2011.01.056
DO - 10.1016/j.brainres.2011.01.056
M3 - Article
C2 - 21276773
AN - SCOPUS:79952535524
VL - 1382
SP - 109
EP - 117
JO - Molecular Brain Research
JF - Molecular Brain Research
SN - 0006-8993
ER -