Sevoflurane exposure alleviate posttraumatic stress disorder by inhibiting extracellular signal-regulated kinase activation in the bed nucleus of stria terminalis in juvenile mice
Objective To investigate the regulatory role of phosphorylated extracellular signal-regulated kinase(p-ERK)in the bed nucleus of stria terminalis(BNST)in alleviating post-traumatic stress disorder in juvenile mice with 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+extracellular signal-regulated kinase(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 for 3 consecutive days for 2 h per day,and mice in group C,group C1,and group C2 were exposed to 30％oxygen for 3 consecutive days for 2 h per day.The mice in group S,group S1,group S2 were treated with sevoflurane on the 1st day,and the model of stress-enhanced fear learning was established.The mice in group C and group S were subjected to trauma scene test on the second day to observe the rigidity behavior of the mice,the percentage of stiff behavior time(T1)was calculated,and six groups of mice were paired with electric shock-new scene on the 3rd day to observe the stiff behavior and the percentage of time of basal stiffness(T2)was calculated;the 6 groups of mice underwent sensitization test on day 4,observed the stiff behavior of mice,and calculated the percentage of time(T3)of mouse sensitization test stiff behavior.Thirty minutes before the sensitiza-tion test,mice in group C2 were intraperitoneally injected with ERK inhibitor U0126 10 mg/kg,mice in group S2 were intraperitoneally in-jected with ERK agonist Honokiol 10 mg/kg,and mice in group C1 and group S1 were intraperitoneally injected with 500 µl normal sa-line,group C and group S were not treated.The expression of p-ERK in bed nucleus of stria terminalis(BNST)of 6 groups of mice was detected by immunohistochemistry,the co-labeling of p-ERK and vesicular glutamate transporter 2(VGLUT 2)in BNST was detected by immunofluorescence in group C and group S.Results Compared with group C,T1 and T3 in group S were significantly decreased(P＜0.05),but T2 had no significant difference(P＞0.05);compared with group C1,the level of T3 in group C2 was lower(P＜0.05),but the level of T2 was not significantly different(P＞0.05);compared with group S1,T3 in group S2 was significantly increased(P＜0.05),and T2 had no significant difference(P＞0.05).Compared with group C,the area of p-ERK positive cells in BNST in group S decreased(P＜0.05);compared with group C1,the area of p-ERK positive cells in group C2 decreased significantly(P＜0.05);compared with group S1 the area of p-ERK positive cells in group S2 increased significantly(P＜0.05);compared with group C2,the area of p-ERK positive cells in group S2 increased significantly(P＜0.05).Group C had more VGLUT2 in ERK-positive neurons activated by BNST,and acti-vated p-ERK co-expressed with VGLUT2,while group S did not.Conclusion Repeated sevoflurane exposure can alleviate PTSD in young mice,which may be caused by inhibition of ERK in excitatory neurons in the bed nucleus of striatum.
SevofluraneExtracellular signal-regulated kinasePost-traumatic stress disorderBed nucleus of stria termi-nalisYoung mice
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