Relationship between histone acetylation and NR2B-CREB-BDNF signaling pathway during sevoflurane-induced cognitive decline in aged mice / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the relationship between histone acetylation and N-methyl-D-aspartic acid (NMDA) receptor subunit 2B (NR2B)-cAMP-response element binding protein (CREB)-brain-derived neurotrophic factor (BDNF) signaling pathway during sevoflurane-induced cognitive decline in aged mice.Methods:Forty-eight SPF healthy male C57BL/6J mice, aged 22 months, weighing 32-40 g, were divided into 4 groups ( n = 12 each) using a random number table method: control group (group C), sevoflurane group (group S), dimethyl sulfoxide (DMSO) plus sevoflurane group (group DS) and histone deacetylase inhibitor vorinostat (SAHA) plus sevoflurane group (group SS). The 100% oxygen was inhaled for 2 h in group C. In S, DS and SS groups, 3.0% sevoflurane was inhaled for 2 h, Morris Water Maze (MWM) test was performed at 24 h after the end of sevoflurane inhalation.SAHA 50 mg/kg was intraperitoneally injected in group SS, and the equal volume of DMSO was given instead in group DS at 2 h before sevoflurane inhalation and at 2 h before MWM test was performed every day.Animals were sacrificed after the MWM test, and hippocampi were isolated for determination of the expression of acetyl-H3 in the nucleus and NR2B, phosphorylated CREB (p-CREB) and BDNF in cytoplasm by Western blot.Real-time polymerase chain reaction was used to determine the expression of NR2B and BDNF mRNA. Results:Compared with group C, the escape latency was significantly prolonged, and the percentage of time spent in target quadrant was decreased, and the expression of acetyl-H3, NR2B, p-CREB, BDNF, NR2B mRNA, and BDNF mRNA was down-regulated in S, DS and SS groups ( P<0.05). Compared with group S or group DS, the escape latency was significantly shortened, the percentage of time spent in target quadrant was increased, the expression of acetyl-H3, NR2B, p-CREB, BDNF, NR2B mRNA, and BDNF mRNA was up-regulated in group SS ( P<0.05). There was no significant difference in each parameter mentioned above between group S and group SD ( P>0.05). Conclusion:Histone acetylation is involved in the pathophysiological mechanism of cognitive decline induced by sevoflurane anesthesia by regulating NR2B-CREB-BDNF signaling pathway in aged mice.