Objective To explore the effect of sodium para-aminosalicylate (PAS-Na) on the expression of gammaaminobutryic acid type A receptor (GABAAR) and gamma-aminobutryic acid transporter (GAT-1) in short-term or subchronic manganese (Mn)-exposed rats.
Methods In the short-term experiment, rats were divided into control, Mn-exposed, lowdose PAS-Na (L-PAS) and high-dose PAS-Na (H-PAS) groups, each subgroup of 10 rats were necropsied at the end of week 7 and 10. In the subchronic experiment, rats were divided into control, Mn-exposed, PAS-Na prevention (P-PAS), and L-PAS, M-PAS (middle-dose PAS-Na) and H-PAS groups, and were observed at week 4, 8, 12 and 18. The mRNA and protein expression of GABAAR and GAT-1 in rat basal ganglia were examined by real-time fluorescence polymerase chain reaction (RT-PCR) and Western blot (WB).
Results In the short-term experiment, on observation week 7, GABAAR protein expression was significantly increased in Mn-exposed group (P < 0.05); on observation week 10, GABAAR and GAT-1 mRNA expression were significantly decreased in Mn-exposed rats (P < 0.05), and L-PAS and H-PAS treatment restored their GAT-1 mRNA expression (P < 0.05). In the subchronic experiment, on obervation week 4, GABAAR mRNA expression was greatly increased in Mn-exposed rats (P < 0.05); on observation week 8, GABAAR mRNA expression was greatly decreased in Mn-exposed rats vs controls (P < 0.05) and increased in P-PAS group vs Mnexposed rats (P < 0.05); however, on obervation week 12, GABAAR protein expression was greatly increased in Mn-exposed rats vs controls (P < 0.05) and decreased in P-PAS vs Mn-exposed rats (P < 0.05); on observation week 18, GABAAR mRNA expression was greatly decreased in Mn-exposed rats vs controls (P < 0.05), and GAT-1 mRNA expression was greatly increased in Mn-exposed rats vs controls (P < 0.05) and decreased in H-PAS vs Mn-exposed rats (P < 0.05).
Conclusion Short-term and subchronic exposure of manganese exhibited obvious toxic effects in the expression of mRNA GABAAR and GAT-1 in basal ganglions of rats. PAS-Na played a preventive intervention role in the GABAAR mRNA or protein expression of subchronic Mn-exposed rats and a therapeutic intervention role in the GAT-1 mRNA expression.
DownLoad: