Exposure to propofol down-regulates myelin basic protein expression in zebrafish embryos: its neurotoxicity on oligodendrocytes and the molecular mechanisms

Abstract

To investigate the mechanism underlying propofol- induced down-regulation of myelin basic protein (MBP) in zebrafish embryos. Zebrafish embryos (6-48 h post-fertilization [hpf]) were randomized into 4 equal groups for exposure to dimethyl sulfoxide (DMSO), 20 μg/mL propofol, 30 μg/mL propofol, or no particular treatment (control group). The larvae were collected at 48 or 72 hpf for detecting the mRNA levels of MBP, Olig1, Olig2, and Sox10 using qRT-PCR (n=80). The protein expression of MBP was quantitatively detected using Western blotting (n=80), and the apoptosis of the oligodendrocytes was investigated using TUNEL staining (n=6). Exposure to 20 and 30 μg/mL propofol caused significant reductions in the mRNA expressions of Olig1, Olig2, and Sox10 at 48 and 72 hpf (P < 0.05) and also in MBP mRNA and protein levels at 72 hpf (P < 0.05). Exposure to 30 μg/mL propofol induced more obvious reduction in MBP protein expression than 20 μg/mL propofol at 72 hpf (P < 0.05), and the exposures resulted in a significant increase of oligodendrocyte apoptosis at 72 hpf (P < 0.05). Propofol exposure reduces MBP expression at both the mRNA and protein levels in zebrafish embryos by down-regulating the expressions of Olig1, Olig2 and Sox10 mRNA levels and increasing apoptosis of the oligodendrocytes.