title: Sodium benzoate exposure downregulates the expression of tyrosine hydroxylase and dopamine transporter in dopaminergic neurons in developing zebrafish.
abstract: BACKGROUND
  Recent data have demonstrated that treatment with sodium benzoate (SB) leads to significant developmental defects in motor neuron axons and neuromuscular junctions in zebrafish larvae, thereby implying that SB can be neurotoxic. This study examined whether SB affects the development of dopaminergic neurons in the zebrafish brain.
  
  
  METHODS
  Zebrafish embryos were exposed to different concentrations of SB for various durations, during which the survival rates were recorded, the expression of tyrosine hydroxylase (TH) and dopamine transporter (DAT) in the neurons in the ventral diencephalon were detected by in situ hybridization and immunofluorescence, and the locomotor activity of larval zebrafish was measured.
  
  
  RESULTS
  The survival rates were significantly decreased with the increase of duration and dose of SB-treatment. Compared to untreated clutch mates (untreated controls), treatment with SB significantly downregulated expression of TH and DAT in neurons in the ventral diencephalon of 3-day post-fertilization (dpf) zebrafish embryos in a dose-dependent manner. Furthermore, there was a marked decrease in locomotor activity in zebrafish larvae at 6dpf in response to SB treatment.
  
  
  CONCLUSIONS
  The results suggest that SB exposure can cause significantly decreased survival rates of zebrafish embryos in a time- and dose-dependent manner and downregulated expression of TH and DAT in dopaminergic neurons in the zebrafish ventral diencephalon, which results in decreased locomotor activity of zebrafish larvae. This study may provide some important information for further elucidating the mechanism underlying SB-induced developmental neurotoxicity.
authors.affiliation: Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong Province, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Chen
authors.forename: Nan-Nan
authors.initials: NN
authors.lastname: Huang
authors.forename: Jin-Tao
authors.initials: JT
authors.lastname: Huang
authors.forename: Shen
authors.initials: S
authors.lastname: Chen
authors.forename: Jinjin
authors.initials: J
authors.lastname: Fan
authors.forename: Chaohong
authors.initials: C
authors.lastname: Li
authors.forename: Fu-Kang
authors.initials: FK
authors.lastname: Xie
mesh_terms: D000818:Animals; D001483:Base Sequence; D018076:DNA, Complementary / Q000235:genetics; D004027:Diencephalon / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000096:biosynthesis* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D005520:Food Preservatives / Q000633:toxicity*; D017403:In Situ Hybridization; D007814:Larva / Q000187:drug effects; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011897:Random Allocation; D020160:Sodium Benzoate / Q000633:toxicity*; D013550:Swimming; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis* / Q000235:genetics; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D018076:DNA, Complementary; D050483:Dopamine Plasma Membrane Transport Proteins; D005520:Food Preservatives; D029961:Zebrafish Proteins; D014446:Tyrosine 3-Monooxygenase; D020160:Sodium Benzoate