The Effect And Mechanism Of Propofol On The Learning And Memory In The Premature Ovarian Failure Mice

Objective:To compare the effect of cisplatin and ovariectomy on mice's learning and memory,andfind a suitable premature ovarian failure model for our study;to research the influence and its possible molecular mechanism of propofol on learning and memory of the mice with premature ovarian failure.Methods:1.ICR mice(female,6-8 weeks)were randomly divided into four groups:control,CDDP,sham-operated and OVX.The general status,oestrous cycle were observed in all mice;and the overian and uterine wet weights of control and CDDP group were also measured.Using HE staining to observe the pathological changes of the ovarian and uterine in the CDDP group.The concentration of FSH,LH,P and E2 in the serum of mice were tested by ELISA,and passive avoidance test were also detected for the reseach of learning and memory ability by observing the the error number and latency.2.ICR mice(female,6?8 weeks)were randomly divided into six groups:sham-operated,Pro50,Pro250,OVX,Pro50+OVX and Pro250+OVX.The general situation of all the mice were observed everyday;and passive avoidance test was used to research the learning and memory ability of each mouse;the expression of GSK-3?,p-GSK-3?-Ser9,CREB,p-CREB-Serl33 and caspase-3 in the hippocampus 1h and 24h after propofol injection were tested by western blot and immunohistochemistry;and we also use Nissl staining to observe the damage of hippocampus neuron.Results:1.The mice in the CDDP group showed significant loss of body weight compared with the control group(P<0.01),and also performed bad general statues and continous diestrous,meanwhile,the overian and uterine wet weights of the CDDP were significant loss;the pathological of the ovarian and uterine in the CDDP showed significant changes;its latency was decreased significant compared with the control group(P<0.01)and its error number was increased significant compared with the control group(P<0.01);the concentration of FSH,LH and E2 in the serum had no important difference between the two group(P>0.05),the concentration of P in the serum of the mice who received cisplatin was significant descreased(P<0.01).There were little change between the weight of ovariectomy and sham-operated mice(P>0.05);the OVX mice showed dysfunction of estrous cycle;its latency was decreased significant compared with the sham-operated group(P<0.01),its error number had no significant difference between the two group(P>0.05);the concentration of FSH and LH in the serum of ovariectomy mice were significant increased(P<0.01);and the concentration of P and E2 in the serum were significant descreased(P<0.01).2.The spontaneous locomotor activity was smiliar between before and after propofol inj ection in each mouse(P>0.05);and compared to the mice in sham-operated group,the memory retention latencies of mice in Pro50,Pro250,and OVX were significantly prolonfed(P<0.0001).3.1h after propofol injection:the subanesthesic and anesthesic dose of propofol can induce down-regulated expression of p-GSK-3?-Ser9,p-CREB-Ser133 and up-regulated expression of caspase-3 in the hippocampus of sham-operated mice,but subanesthesic dose of propofol can up-regulate the expression of p-GSK-3?-Ser9 in the hippocampus of OVX mice;24h after propofol inj ection:the subanesthesic and anesthesic dose of propofol can induce up-regulated expression of caspase-3 in the hippocampus of sham-operated mice,meanwhile,subanesthesic dose of propofol can up-regulate the expression of p-GSK-3?-Ser9,p-CREB-Ser133 and down-regulate the expression of caspase-3 in the hippocampus of OVX mice;compared to the mice in sham-operated group,there were some neuron loss in the hippocampus of mice in Pro50,Pro250,OVX and Pro250+OVX group,and the contour of the cells are vague and have been disordered arrangement,and tigroid body was decreased in the neuron;however,the hippocampus of mice in Pro50+OVX group can only see little changes in the cell morphology compared to the mice in OVX group.Conclusions:1.The ovariectomy mice model can well simulate the symptom of premature ovarian faliure,and the influence of learning and memory was less than the cisplatin.2.propofol can dose dependently damage the memory consolidation of mice received sham operation;while subanesthesic dose of propofol can promote the memory consolidation of mice received ovariectomy;3.propofol can down-regulate expression of p-GSK-3?-Ser9,p-CREB-Ser133 and up-regulate expression of caspase-3 in the hippocampus of mice received sham operation,increasing the damage of neuron in the hippocampus;meanwhile,subanesthesic dose of propofol can up-regulate expression of p-GSK-3?-Ser9,p-CREB-Ser133 and down-regulate expression of caspase-3 in the hippocampus of mice received ovariectomy,improving the damage of neuron in the hippocampus.