Effect of propofol anesthesia on the expression of BDNF mRNA and proBDNF/mBDNF in hippocampus and long-term spatial learning/memory functions in neonatal rats / 解放军医学杂志

ABSTRACT

Objective To investigate the effect of propofol anesthesia on the expression of brain-derived neurotrophic factor (BDNF) mRNA and BDNF precursor (proBDNF)/mature (mBDNF) in hippocampus of neonatal rats, and the relationship with long-term spatial learning/memory functions. Methods One hundred and eight SD rats aged 7 days weighing 12-16g were randomly divided into 3 groups (36 each) control group (C), propofol anesthesia once group (P1) and multiple propofol anesthesia group (P2). Rats in group C were intraperitoneally injected with 0.9% normal saline, 7.5ml/kg once a day for 7 days; rats group P1 were injected normal saline 7.5ml/kg once a day for 6 days and propofol 75mg/kg on the last day; rats group P2 received propofol 75mg/kg once a day for 7 days. Fifteen minutes after the last intraperitoneal injection, blood gas analysis and blood glucose detection were performed in 6 rats of each group. The hippocampal tissues were taken at 6, 24, 48, 72h and 30d to measure BDNF mRNA, proBDNF and mBDNF by RT-PCR and Western blotting after the completion of the injection. Learning and memory functions were assessed using Morris water maze at 25 days old of rats. Results The expression of BDNF mRNA and mBDNF protein increased gradually in hippocampus, while of proBDNF protein and the ratio of proBDNF/mBDNF decreased gradually in group C. In group P1, the BDNF mRNA and mBDNF protein were down-regulated, the ratio of proBDNF/mBDNF were up-regulated (P<0.05), the escape latency was prolonged, and space exploration time was shortened compared with group C (P<0.05). Compared with group C and group P1, the BDNF mRNA and mBDNF protein were down-regulated significantly, the proBDNF protein and the ratio of proBDNF/mBDNF were up-regulated observably (P<0.05), the escape latency was distinctly prolonged, and space exploration time was shortened apparently in group P2 (P<0.05). Conclusions Propofol anesthesia may impair the learning and memory function of infancy in rats, the effects are more obvious in repeated propofol anesthesia than in single ones. The mechanisms may be related to the changed expression of BDNF mRNA and the ratio of proBDNF/mBDNF.