Anti-parkinsonian effects of octacosanol in 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-treated mice.
Our previous research showed that octacosanol exerted its protective effects in 6-hydroxydopamine-induced Parkinsonian rats. The goal of this study was to investigate whether octacosanol would attenuate neurotoxicity in 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP)-treated C57BL/6N mice and its potential mechanism. Behavioral tests, tyrosine hydroxylase immunohistochemistry and western blot were used to investigate the effects of octacosanol in a mouse model of Parkinson's disease. Oral administration of octacosanol (100 mg/kg) significantly improved behavioral impairments in mice treated by MPTP and markedly ameliorated morphological appearances of tyrosine hydroxylase-positive neuronal cells in the substantia nigra. Furthermore, octacosanol blocked MPTP-induced phosphorylation of p38MAPK and JNK, but not ERK1/2. These findings implicated that the protective effects afforded by octacosanol might be mediated by blocking the phosphorylation of p38MAPK and JNK on the signal transduction in vivo. Considering its excellent tolerability, octacosanol might be considered as a candidate agent for clinical application in treating Parkinson's disease.
Department of Neurobiology, Beijing Institute of Geriatrics, Xuanwu Hospital of Capital Medical University, Beijing 100053, China.
Tao
T
Wang
Department of Pharmacology, Institute of Basic Medical Sciences, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100005, China.
Yanyong
Y
Liu
Department of Pharmacology, Institute of Basic Medical Sciences, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100005, China.
Nan
N
Yang
Department of Pharmacology, Institute of Basic Medical Sciences, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100005, China.
Chao
C
Ji
Department of Neurobiology, Beijing Institute of Geriatrics, Xuanwu Hospital of Capital Medical University, Beijing 100053, China.
Piu
P
Chan
Department of Pharmacology, Institute of Basic Medical Sciences, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100005, China.
Pingping
P
Zuo
Parkinson's disease; c-Jun N-terminal kinase; mitogen-activated protein kinase; neural regeneration; neuroprotecion; p38MAPK; substantia nigra