Fucoidan protects against dopaminergic neuron death in vivo and in vitro.
Parkinson's disease is a neurodegenerative disorder of uncertain pathogenesis characterized by a loss of dopaminergic neurons in substantia nigra pars compacta, and can be modeled by the neurotoxin 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). Oxidative stress may contribute to MPTP- and Parkinson's disease-related neurodegeneration. Fucoidan is a sulfated polysaccharide extracted from brown seaweeds which possesses a wide variety of biological activities including potent antioxidative effects. Here we investigated the effect of fucoidan treatment on locomoter activities of animals, striatal dopamine and its metabolites and survival of nigral dopaminergic neurons in MPTP-induced animal model of Parkinsonism in C57/BL mice in vivo and on the neuronal damage induced by 1-methyl-4-phenylpyridinium (MPP(+)) in vitro, and to study the possible mechanisms. When administered prior to MPTP, fucoidan reduced behavioral deficits, increased striatal dopamine and its metabolites levels, reduced cell death, and led to a marked increase in tyrosine hydroxylase expression relative to mice treated with MPTP alone. Furthermore, we found that fucoidan inhibited MPTP-induced lipid peroxidation and reduction of antioxidant enzyme activity. In addition, pre-treatment with fucoidan significantly protected against MPP(+)-induced damage in MN9D cells. Taken together, these findings suggest that fucoidan has protective effect in MPTP-induced neurotoxicity in this model of Parkinson's disease via its antioxidative activity.
Luo
Dingzhen
D
Key Laboratory of Neurodegenerative Diseases of the Ministry of Education, Capital Medical University, Beijing, PR China.
Zhang
Quanbin
Q
Wang
Haomin
H
Cui
Yanqiu
Y
Sun
Zuoli
Z
Yang
Jian
J
Zheng
Yan
Y
Jia
Jun
J
Yu
Fen
F
Wang
Xuan
X
Wang
Xiaomin
X
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D004298:Dopamine / Q000172:deficiency / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D020267:MPTP Poisoning / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011134:Polysaccharides / Q000494:pharmacology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D000975:Antioxidants; D018696:Neuroprotective Agents; D011134:Polysaccharides; D015102:3,4-Dihydroxyphenylacetic Acid; C007789:fucoidan; D014446:Tyrosine 3-Monooxygenase; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine