ABSTRACT
Objective To investigate the effect of celastrol on space learning capability and expressions of beta-amyloid (Aβ) 40 and Aβ42 in hippocampus in APPswe/PS1dE9 double transgenic mouse after partial hepatolobectomy.Methods The 3-month-old APPswe/PS1dE9 double transgenic mice (n =96) were randomly divided into three groups according to the random number table method.Surgery group (group S, partial hepatolobectomy;n =32), celastrol group (group C, injections of dimethyl sulphoxide/DMSO and celastrol for 3 days before undergoing partial hepatectomy, on the surgery day, and for a further 4 days after surgery;n =32), and DMSO group (group D, injections of DMSO for 3 days before undergoing partial hepatectomy, on the surgery day, and for a further 4 days after surgery;n =32).Eight mice were selected randomly in each group and were Morris-water maze trained for continuous 5 days.Theirs learning and memory abilities were evaluated at 1,3, 7 and 14 d after surgery, respectively.Hippocampus was collected and the changes of β40 and Aβ42 were measured by enzyme-linked immunosorbent assay (ELISA) at the time set in advance in each group.Results The average escape latency of group C was significantly shorter than groups S and D at 3, 7 and 14 d after partial hepatectomy (P ＜ 0.05).Times of passing through the platform groups S and D were significantly less than group C (P ＜ 0.05).The expressions of Aβ40/Aβ42 in group C were lower than group S and group D at 1, 3, 7 and 14 d after partial hepatectomy (P ＜ 0.05).Conclusions Through decreasing the expressions of Aβ40 and Aβ42 in hippocampus,celastrol improves the space learning capability in APPswe/PS1dE9, the double transgenic mouse after partial hepatolobectomy.
ABSTRACT
Objective To study the influences of hepatolobectomy on space learning capability and the expressions of Drebrin and PSD95 in the hippocampus in APP/PS1 transgenic mouse model of Alzheimer's disease.Methods A total of fifty-four 3-month-old APP/PS1 transgenic mouse were randomly divided into 3 groups:3-month-old control group,sham surgery group,hepatolobectomy group,3-month-old littermates control group and 6-month-old control group.Morris water maze test was used to observe space learning capability on the 1st,3rd,7th,14th day after surgery,meanwhile the expressions of Drebrin and PSD95 in hippocampus were measured by Western blotting.Results Compared with the sham surgery group,the results of the Morris water maze test were decreased in hepatolobectomy group at day 3,7,14 after surgery [(62.9±6.9) s vs.(35.7±12.2) s,(66.3± 9.5) s vs.(39.3±8.3) s,(67.1±7.5) s vs.(32.6±14.1) s],and 6-month-old control group [(75.9±12.1) s] (all P＜0.05).The escape latency were (62.9±6.9)s,(66.3±9.5)s,(67.1± 7.5)s and (75.9±12.1)s,the probe trials were (2.1±0.7) times,(1.83±1.5) times,(2.5±1.9) times and (1.8±0.8) times respectively in hepatolobectomy group at day 3,7,14 after surgery and 6-month old control group.No significant differences in the results of the Morris water maze test were found among 3-month-old control group,3-month-old littermates control group,and sham surgery group.Compared with 3-month-old control group and sham surgery group atday 1,3,7,14 after surgery the expressions of Drebrin were decreased in 6-month-old control group and the hepatolobectomy group at the same time points.Meanwhile,the expression of Drebrin in hepatolobectomy group was increasedat day 14 versus day 7 after surgery.Compared with 3 month-old control group,the expression of Drebrin was increased at day 7 after sham surgery.Compared with 3-month-old control group and sham surgery group at day 3,7 and 14,the expressions of PSD95 were decreased in hepatolobectomy group at the same time points.Compared with 3-month-old control group,the expression of PSD95 was increased in sham surgery group at 7th day (P＜0.05).Between 3 month-old control group and 3-month-old littermates control group,the expressions of Drebrin and PSD95 had no significant differences.Concltsions Hepatolobectomy can impair the capabilities of space learning and memory in 3-month-old APP/PS1 transgenic mice,which may be associated with the decreased expressions of Drebrin and PSD95 in hippocampus.
ABSTRACT
Objective To investigate the effects of partial hepatectomy on spatial learning and memory abilities and the expression of spinophilin,which was used as a marker to quantify changes in dendritic spine density in the hippocampus of APP/PS1 transgenic mice.Methods 3-month-old and 6-month-old male APP/PSI transgenic mice and 3-month-old wild-type male littermates were divided into five groups based on their genetic background:3-month-old control (group A,n =8),anesthesia (group B,n =32),surgery (group C,n =32),littermates control(group D,n =8),6-month-old control (group E,n =8).According to the different time points at day 1,3,7,14 after anesthesia or surgery,group B and C were divided randomly into 4 subgroups:B1,B3,B7,B14 and C1,C3,C7,C14.The spatial learning and memory abilities were detected by Morris water maze test in each group at the corresponding time points.Meanwhile,spinophilin expression was detected by Western blot and Immunocytochemistry in the hippocampus.Results Compared with the same time point subgroup B,the latency to find a hidden platform was longer and the frequency of passing through the platform was decreased in Group C at day 3,7,14(P ＜ 0.05).No significant differences were found among group A,group D,and group B (P ＞ 0.05).The grey value and Western blot relative integrated optical density of spinophilin in group A(1 609 453 ±92 801/0.471±0.015),approached the Group D(1 329 398.4±77 783/0.434±0.008)(P＞0.05),were significantly increased compared with that(801 678 ± 10 505/0.053 ± 0.003) in group E (P ＜ 0.01).Compared with the Group A,the same time point subgroup B and subgroup C14,the grey value and Western blot relative integrated optical density of spinophilin were decreased in Group C at day 1,3,7 (P ＜ 0.05).Conclusion Partial hepatectomy can impair spatial learning and memory abilities of the APP/PS1 transgenic mice,which is closely related to the decrease expression of spinophilin in hippocampus.