Abstract: Objective: Investigating the role of phosphorylated extracellular kinase (ERK) in the bed nucleus of stria terminalis of juvenile mice after multiple sevoflurane exposure. Methods: SPF male C57/BL mice aged 3 weeks were randomly divided into 6 groups: control group (group C, n = 11), sevoflurane group (group S, n=12), control + vehicle group (group C1, n= 5), control + ERK inhibitor group (group C2, n= 5), sevoflurane + vehicle Group (group S1, n=5), sevoflurane + ERK agonist group (group S2, n= 5). Mice in group S, group S1, and group S2 were exposed to 3% sevoflurane + 30% oxygen two hours per day for three consecutive days, and mice in Group C, Group C1, and Group C2 were exposed to 30% oxygen. One day after sevoflurane exposure, mice received the electric footshock intermittently, and the stress-enhanced fear learning model was established. The trauma context test was performed on the second day, the matching new scene test was performed on the third day, and the sensitization test was performed on the fourth day.30 minutes before the sensitization test, mice in Group C2 were intraperitoneally injected with ERK inhibitor U0126(10 mg/kg) , and mice in group S2 were intraperitoneally injected with ERK agonist Honokiol (10 mg/kg) , mice in Group C1 and S1 were intraperitoneally injected with 500 ul saline, the time of freezing behavior was recorded and the freezing level was calculated. The expression of p-ERK was detected by immunohistochemistry and theco-labeling of p-ERK and VGULT2 was detected by immunofluorescence. Results: Compared with C group, the freezing level in group S was significantly decreased (p 0.05). Compared with Group C, the p-erk positive cells in the bed nucleus of stria terminalis in group S were significantly increased (p 0.05). Compared with Group C1, the freezing level of Group C2 was significantly lower (p 0.05), and the freezing level of group S2 was significantly higher than group S1(p 0.05). The results of immunofluorescence showed that the activated ERK and VGLUT2 were co-expressed in the bed nucleus of stria terminalis. Conclusion: Multiple sevoflurane exposure could alleviate PTSD in young mice, which may be caused by inhibiting ERK in excitatory neurons in bed nucleus of stria terminalis.
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