Analgesia Fucoidan protects against dopaminergic neuron death in vivo and in vitro

a r t i c l e i n f o Keywords: Fucoidan Neuroprotection Antioxidant activity Oxidative stress 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine Parkinson's disease 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. Parkinson's disease is a progressive neurological disorder characterized by the loss of the dopamine in the striatum, which occurs mainly due to the death of the dopaminergic neurons in the substantia nigra compacta pars. A meperidine analog, 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP), causes selective nigral dopaminergic lesions, resulting in Parkinsonian syndromes in humans, primates and mice (Bloem et al., 1990). Numerous studies have subsequently demonstrated that the toxicity of MPTP depends on its conversion to its active metabolite, 1-methyl-4-phenylpyridinium (MPP +) (Tipton and Singer, 1993). MPP + rapidly accumulates in dopaminergic neurons via the plasma membrane dopamine transporter. Once inside cells, MPP + accumulates in mitochondria where it inhibits complex I of the mitochondrial electron transport chain. This leads to impairment of energy production and increased free radical generation, and eventually causes dopaminergic neuron death (Alcaraz-Zubeldia et al., 2001; Thomas et al., 2000). It was reported that MPTP might preferentially target dopaminergic neurons rather than other neurons in the same region. Such toxicity on the dopaminergic nigrostriatal system seems reasonable since the …