Propofol upregulates the expressions and secretions of brain derived neurotrophic factor in rat hippocampal astrocytes via extracellular signal-regulated kinase signaling pathway

Abstract

Objective To detect the expression level and secretion change of brain derived neurotrophic factor (BDNF) in rat hippocampus and hippocampal astrocytes induced by propofol and address its mechanism. Methods According to the treatment time of propofol, 24 rats were randomly divided into three groups, i.e. 0, 45 min and 90 min groups. Rats were administrated intraperitoneally with propofol (10 g/L, 100 mg/kg body weight). The levels of BDNF mRNA and glial fibrillary acidic protein (GFAP) in rat hippocampus were evaluated by real time polymerase chain reaction (PCR) and immunohistochemistry respectively. Primary cultured hippocampal astrocytes in vitro were divided into 3 groups: Control group (group Ctrl), Propofol group (group Pro), and Inhibitor PD98059+ Propofol group (group Pro-PD). In group Pro-PD, astrocytes were pretreated with 10 μmol/L extracellular signal regulated kinase (ERK) inhibitor PD98059 for 2 h, then incubated with 10 μmol/L propofol for 24 h. Finally cell apoptosis and the expression and secretion levels of BDNF were examined. Results Forty-five min and 90 min after injection of propofol, the mRNA levels of BDNF in the hippocampal tissue were 1.20±0.05 fold and 0.86±0.04 of the expression level in group 0 min respectively (P 0.05). The BDNF mRNA level of hippocampal astrocytes in group Pro was 1.15±0.04 fold of that in group Ctrl (P<0.05). The BDNF mRNA level in group Pro-PD was 0.92±0.05, which was significantly lower than that of group Pro (P<0.05). The BDNF secretion level of hippocampal astrocytes in group Pro was (62±4) ng/L, which was higher than(49±3) ng/L in group Ctrl. The BDNF secretion level in group Pro-PD was (44±3) ng/L, which was significantly lower than that of group Pro(P<0.05). Conclusions Propofol activated the rat hippocampal astrocytes and enhanced the expression level and secretion of BDNF in astrocytes through ERK signaling pathway. Key words: Propofol; Astrocyte; Extracellular signal-regulated kinase; Brain derived neurotrophic factor