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Objective The present study is to elucidate the protective effect of Polysaccharide from Spirulina Platensis (PSP) on dopaminergic neurons of MPTP induced C57BL/6J mice.Methods Animals were divided into 5 groups:(1) NS (i.g.) × 10 d; (2) NS (i.g.) × 10 d + MPTP (15 mg/kg,i.p.) × 4; (3) PSP (200 mg/kg,i.g.) × 10 d + MPTP (15 mg/kg,i.p.) × 4;(4) PSP (400 mg/kg,i.g.) × 10 d + MPTP (15 mg/kg,i.p.) × 4; (5) PSP (800 mg/kg,i.g.) × 10 d + MPTP (15 mg/kg,i.p.) × 4.Immunohistochemistry assay,RT-PCR,HPLC-ECD were used to detect the protein and mRNA levels of tyrosine hydroxylase (TH) and dopamine transporters (DAT) in the substantia nigra (SN),the content of dopamine (DA) and its metabolites:3,4-dihydroxyphenyl acetic acid (DOPAC),homovanilic acid (HVA) in the striatum (Str).The results showed that,compared with control group,the TH and DAT immunoreactive stain in MPTP group was significantly decreased in the SN (P < 0.01),as well as the TH mRNA and DAT mRNA (P<0.01).The content of DA,DOPAC and HVA in Str was also decreased (P < 0.01).While in PSP 800 mg/kg pretreatment group,the protein and mRNA levels of TH and DAT in the SN were increased (P < 0.05),and the content of DA,DOPAC and HVA in the Str was also increased compared with MPTP group (P < 0.05).The results suggested that PSP plays a protective effect on MPTP-damaged dopaminergic neurons of C57BL/6J mice.