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Objective:To investigate the effect of repetitive transcranial magnetic stimulation (rTMS) on the hippocampal lipidome in a rat model of chronic unpredictable stress(CUS).Methods:Twenty-four SD rats were randomly assigned to the following 3 groups ( n=8 for each group): sham group, CUS group and CUS+ rTMS group. The sham group received only sham stimulation and rats in the CUS and CUS+ rTMS group were subjected to CUS stimulation. Then, rats received 5 Hz rTMS (5 Hz, 1.26 Tesla) or sham rTMS for 7 days. After the last stimulation, all rats underwent sucrose preference test, open filed test and forced swimming test so as to observe the effect of rTMS on depressive behavior. Then, rats were sacrificed, and the levels of lipid composition in hippocampus were determined by high performance liquid chromatography mass spectrometry and analyzed by lipid search software version 4.1 and SIMCA-P 14.1.The software of SPSS 19.0 was used for statistical analysis. Univariate analysis of variance was used for comparison among groups, and Tukey test was used for multiple comparison. Results:(1)There were significant differences in open field test, sugar preference test and forced swimming test among the three groups( F=6.853-7.466, all P<0.05). In the open field experiment, the exploring time and percentage of movement distance in central area of rats in CUS group((50.72±6.38)s, (11.41±1.55)%) was significantly less than that of sham group ((86.06±7.31)s, (18.60±1.21)%) and CUS+ rTMS group((79.87±7.87)s, (16.74±1.27)%)(all P<0.05). The results of sucrose preference test showed that the percentage of sucrose intake of rats in CUS group ((37.63±6.06)%) was significantly lower than that in sham group ((68.30±6.39)%) and CUS+ rTMS group ((62.68±5.50)%)(both P<0.05) . In forced swimming test, the immobility time of rats in CUS group ((137.60±13.36)s) was significantly longer than that of sham group ((80.57±10.36)s)) and CUS+ rTMS group ((86.14±11.49)s) (both P<0.05). (2)The levels of lipid composition in hippocampus were significantly different in the three groups( F=3.826-15.440, all P<0.05). The contents of phosphatidylethanolamine (PE) ((20 850±956.56)×10 7, (24 133.33±1 242.04)×10 7), phosphatidylinositol (PI) ((788.78±136.11)×10 7, (953.65±131.26)×10 7), lysophosphatidylcholine (LPC) ((340.29±35.66)×10 7, (275.32±35.78)×10 7), creatine phosphate (CerP) ((239.65±18.14)×10 7, (293.82±38.28)×10 7), sphingosine (So) ((22.96±4.04)×10 7, (15.36±3.87)×10 7), diglyceride (DG) ((3.35±0.85)×10 7, (4.57±1.02)×10 7) and monoglyceride (MG) ((6.71±0.82)×10 7, (7.94±0.91)×10 7)in hippocampus of rats in CUS group were significantly higher than those of sham group(all P<0.05), while the phosphatidic acid(PA) ((424.52±33.38)×10 7, (509.22±42.09)×10 7) and acyl carnitine(AcCa) ((2.68±0.33)×10 7, (3.39±0.33)×10 7) decreased(both P<0.05). Compared with CUS group, the contents of PE(21 816.67±928.26)×10 7, PI(83.16±91.52)×10 7, LPC(323.59±33.91)×10 7, CerP(236.39±32.02)×10 7, So(23.35±4.46)×10 7, DG(3.16±0.85)×10 7 and MG(7.03±0.26)×10 7 in the hippocampus of CuS+ rTMS group decreased, while the contents of PA(421.55±44.28)×10 7 and ACCA(2.56±0.32)×10 7 in the hippocampus of CUS+ rTMS group increased (all P<0.05). Conclusion:The levels of glycerophospholipids, glyceroglycerides, sphingolipids, fatty acids and other lipids in the hippocampus of CUS model rats are abnormal. And the 5 Hz rTMS intervention can ameliorate the depression like behavior and the disturbances of lipid in hippocampus of CUS model rats.
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Objective To investigate the effects of gastrodin on neural function and the expression of myelin basic protein (MBP) and neurofilament high molecular weight (NFH) in the striatum during cerebral ischemiareperfusion in mice.Methods 36 Kunming mice were randomly divided into sham group,MCAO group and gastrodin (GAS) group.The middle cerebral artery occlusion(MCAO) was established by artery embolization.The mice in sham group were received fake surgery and saline,and the mice in MCAO and GAS group were exposed to MCAO,and received saline and GAS (100 mg/(kg · d)) injection,respectively,immediately after the operation for 7 days.On the 8th day of operation,the neurological severity scores of the mice were observed and the volume ratio of the cerebral infarction was estimated by triphenyl tetrazolium chloride (TTC) staining.Immunohistochemistry was used to detect the MBP and NF-H in the striatum.Results (1) The mice in MCAO group showed significant neurologic deficient in comparison with sham group,and the neurological severity scores of gastrodin group(3.13±0.64) were significantly higher than that(1.38±0.52) of MCAO group (P＜0.05).(2) Results of TTC staining showed that the infarction volume was obviously larger in the injured cerebral tissue in MCAO group in comparison with sham group,and the volume ratio of the cerebral infarction significantly decreased after the intervention with GAS (P＜0.05).(3) The integral optical density of MBP(272968.14±1215.23) and NF-H(12 142.73±47.16) in MCAO group decreased as compared to that((43 855.23±2434.16),(275 321.00±926.15)) in sham group and GAS group((321 531.2±2376.14),(106 135.73±598.15)) (P＜0.05).Conclusion GAS can improve neural function of mice after middle cerebral artery occlusion,and it may play an important role in protecting myelin and nerve fibers of striatum.
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Objective To investigate the effect of quetiapine (QUE) on the memory and doublecortin (DCX) expression in the hippocampus of C57BL/6 mice with cuprizone (CPZ)-induced schizophrenia in C57BL/ 6 mice.Methods 1％ dimethyl sulfoxide (DMSO) was used as a vehicle to dissolve QUE.Three group of mice,16 in each of three groups,were treated with vehicle (control group),0.2％ CPZ alone (CPZ group) or 0.2％ CPZ combined with 10 mg· kg-1 · d-1 QUE (QUE+CPZ group) for six weeks,respectively.Spatial working memory was evaluated by Y-type maze test 24 hours after the completion of the treatment period.The number of DCX positivenew neurons was calculated by immunofluorescence staining assay.The expression of Notch1 and Hes1 mRNA were detected by reverse transcription-polymerase chain reaction (RT-PCR) assay.Results (1) Y-maze test:CPZ group achieved a much lower percentage of correct alternation than control group ((22.70±6.70) ％ vs (57.69 ±6.70)％) in Y-maze test (P＜0.05).The percentage of correct alternation in CPZ + QUE group ((54.69± 10.06) ％) was significantly increased compared with CPZ group (P＜0.01).CPZ mice exhibited significant spatial working memory impairment.(2) Immunofluorescence staining:the number of DCX-positive cells in the hippocampus of the CPZ group (6342.85± 1801.72) was significantly decreased compared with that in control group (19428.57±2507.13) (P＜0.01),and it was reversed by QUE intervention (15928.57±2049.97).(3) RT-PCR:the Notch1 and Hes1 mRNA expression in CPZ group were significant lower than that in sham and CPZ + QUE group,(Notch1 (0.97±0.29) vs (0.23±0.20),P＜0.01);Hes1 (1.00±0.41) vs (0.38±0.30),P＜0.01),and there was no significant difference between sham group and CPZ + QUE group.Conclusion QUE is helpful to relieve CPZ-induced cognitive impairment and decreases expression of DCX in hippocampal,which may be related with activation of Notch1 pathway.
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Objective To investigate the effect of quetiapine on the behavior and expression of pERK1/2 in chronic unpredictable stress(CUS) model rats.Methods 32 adult male Sprague Dawley rats were randomly divided into four groups (n =8 for each group):control group,CUS group,CUS + QUE (5 mg/kg,L) group and CUS + QUE(10 mg/kg,M)group.The rats in control group were left undisturbed in their home cage for 28 days and the other groups were exposed to 28 consecutive days of CUS,then the rats in control group and CUS group were treated with 1％ DMSO in saline (5 ml/kg,intraperitoneal injection),the rats in CUS + QUE (L)group and CUS + QUE(M) group respectively treated with quetiapine (5 mg/kg)or quetiapine(10 mg/kg) for consecutive 7 days.The weight data of each group were recorded,and the behavioral changes in these rats were analyzed by open field test and forced swimming test;and the expression of pERK1/2 was measured by Western blot.Results (1)Compared with control group,quetiapine (10 mg/kg) ameliorated the inhibition of body weight gain that induced by chronic unpredictable stress (P ＜ 0.05),but quetiapine (5 mg/kg) did not have this effect.(2)Open field and Forced swimming test showed significant difference (P ＜ 0.05) of horizontal motion distance (F =17.846),the number of central region entering(F=4.720) and the immobility time(F=26.090) in each group.And these tests showed that horizontal motion distance and the number of central region entering in CUS group ((6696.30 ±1061.19)mm,(19.63 ±9.15)times) were significantly lower than that of control group ((10824.61 ± 1399.37) mm,(37.75 ± 13.02) times) and CUS + QUE (M) group ((9637.51 ± 1630.16) mm,(32.38 ± 6.23)),while the immobility time (110.73 ± 15.98)s were significantly higher than that of control group((66.13 ± 5.18)s)and CUS + QUE (M) group((73.40 ± 11.99) s,P ＜ 0.05).But there was no significant difference between that of CUS group and CUS + QUE(L) group(P＞0.05).(3)The expression of pERK1/2 in CUS group showed significant decrease when compared with control group or CUS + QUE (M) group,but showed no significant difference with CUS + QUE(L) group(F=6.641,P＜ 0.01).Conclusion Quetiapine can ameliorate depressive-like behaviors induced by chronic unpredictable stress,and this effect may be carried out by up-regulation the expression of pERK1/2 in the hippocampus.
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Objective To investigate the effect of rosmarinic acid on the behavioral changes in enhanced single prolonged stress (ESPS) model rats and the levels of interlukin-1β (IL-1β) and interlukin-6 (IL-6) in the hippocampus.Methods 48 adult male Sprague Dawley rats were randomly divided into six groups (n =8):Control group,Control + RA (L) group,Control + RA (H) group,ESPS group,ESPS + RA (L) group and ESPS + RA (H) group.Behavioral changes of these rats were analyzed by open field test and elevated plus-maze.The levels of IL-1 β and IL-6 were measured by enzyme linked immunosorbent assay (ELISA).Results (1) Open field test showed that the number of central region entering and the fraction of time exploring in center of ESPS group were significantly reduced than that of Control group ((18.13 ± 10.15) times,(26.68 ± 10.06) ％) and ESPS + RA (H) group ((16.88 ± 8.81) times,(25.08 ± 8.52) ％) (P ＜ 0.05).And it showed no significant difference among Control + RA(L) group,Control + RA(H) group and Control group.Meanwhile,there was also no statistic difference between ESPS group and ESPS + RA(L) group.(2) Elevated plus-maze test showed that percentages of open arm entries and fraction of time exploring in open arm in reference to total number of entries into all arms and total time spent on all arms in ESPS group were significantly reduced than that of Control group((37.38 ± 8.24)％,(17.63 ±4.74)％) and ESPS + RA(H) group((33.72 ±9.49)％,(16.99 ±4.28)％) (P ＜ 0.05),but there was no significant difference between that of ESPS group and ESPS + RA(L) group(P＞0.05).It also showed no significant difference among Control + RA (L) group,Control + RA (H) group and Control group.(3) Compared with ESPS group,RA(10mg/kg) reduced the levels of IL-1β and IL-6 in the hippocampus,but RA(5mg/kg) did not have this effect.(4) Correlation analysis results showed the level of IL-1β in the hippocampus was negatively related with the ameliorated PTSD-like behaviors of ESPS exposure rats.Conclusion RA can ameliorate PTSDlike behaviors of ESPS exposure rats,and this effect may be carried out by down-regulating the levels of IL-1β and IL-6 in the hippocampus,especially the IL-1β.
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Objective To study the changes of negative symptoms in PCP-induced schizophrenia rat model.Methods Thirty newborn female SD rats randomly divided into control group,PCP-week 6 group and PCP-week 10 group( n=10 in each group).Perinatal rat treated with PCP ( 10 mg/kg) on postnatal days 7,9 and 11(10 mg/kg,ip),and sucorse intalce test(SIT),forced swimming test(FST) and resident-intruder test(RIT) were used to test the emotional and negative symptoms.Results In the SIT,there was no difference between control and PCP groups (con:(28.24 ±0.86) ml/kg; week 6:(26.57 ± 1.01 ) ml/kg; week 10:(27.98 ±0.99) ml/kg,F =12.35,P ＞ 0.05 ).In the FST,PCP model rats showed longer still time ( con:(39.32 ± 1.98 ) s ; week 6:(52.39 ± 1.66)s,week 10:(55.56 ± 1.49)s,F=3.99,P＜ 0.05 ).In the RIT,PCP models rats showed less explore time ( (40.31 ± 13.56)s vs (63.90 ± 13.12)s,(43.65 ±12.86 )s vs (65.18 ± 15.12)s,P ＜ 0.05 ) and more escape time ((19.33±2.26) s vs (9.26 ± 1.32) s,(17.79 ±2.99) s vs (9.38 ± 1.36) s,P＜ 0.05).Conclusion Perinatal PCP injection can induce the long-lasting negative-symptoms changes.
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Objective To observe the effect of fluoxetine on the single prolonged stress model which mimic the post-traumatic stress disorder (PTSD). Methods Rats receiving single prolonged stress (SPS) (2 h restraint + 20 min FST + anaesthesized to lose consciousness with ethylether) or not were given fluoxetine or tap water for 15 days. Elevated plus maze(EPM),open-field test(OF) and morris water maze(MWM) tests were used to evaluate rats' fear response to environment,high alertness,anxiety & depression behavior,and learning and memory ability. Results In open field test, group of fluoxetine(F1 (8895. 85 ± 599. 78) mm, (40. 23 ±4. 32) s;F2 (8654.07 ±866.05)mm,(41.57 ±4.34)s, P<0.05) showed significant increase in activity times and horizontal motion distance compared with group of SPS (4678.85 ±495.33)mm, (22.15 ±3.43)s, P<0.05). In EPM experiment,group of fluoxetine(F1 (32. 62 ± 4. 57)% , (17. 58 ± 3. 23)% ; F2 (39. 75 ± 4. 46)% , (19. 74 ± 4.44) %) showed significant increase in percentage of the open-arm into the maze and percentage of the open arm pause compared with group of SPS ((23.67 ±2. 87)% ,(12.46 ±2.55)% , P<0.05). In MWM experiment,the escape latency of the SPS group increased significantly in comparison to that in sham group (P<0.01) and fluoxetine group. Fluoxetine significantly reversed the SPS-induced decrease in time spent in the target quadrant (P< 0.05). Conclusion Added fluoxetine can obviously improve rats' fear response to environment ,high alertness ,anxiety & depression behavior as well as learning and memory ability.
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Objective To investigate the effect of sertraline on the viability and the expression of tyrosine hydroxylase (TH) and phosphorylated ERK1/2 in NGF-induced rat pheochromocytoma (PC12) cells.Methods NGF-induced PC12 cells were pretreated or directly treated with different concentrations of sertraline for 24 or 48 hours and the pretreated groups were then subjected to serum withdrawal condition. Then cell viability was determined by the cell counting Kit-8 (CCK-8). The expression of Tyrosine hydroxylase (TH) and pERK1/2in NGF-induced PC12 cells was determined by immunohistochemistry and western blot respectively. Results The viability of NGF-induced PC12 was improved after administration with sertra]ine. After 24h sertraline administration, the cells activity of PC 12 cells at 20μM ( 1.32 ± 0. 11 ) , 10μM ( 1. 17 ± 0.05 ) of direct effect, and 20μM ( 1.15 ±0.11 ) of protect effect increased dramatically as compared with control group. But high dose ( 50μM )sertraline express high toxic effect to PC12 cells. The expression of TH was increased by sertraline 20 μM at both 24h(ratio of TH/β-actin = 1.27 ±0.05) and 48h(ratio of TH/β-actin = 1. 23 ±0.08) compare with control group,and the expression of pERK1/2 also increased dramatically by sertraline 20 μM at both 24h (ratio of (pERK1/2)/β-actin = 1.41±0.05) and 48h( ratio of (pERK1/2)/β-actin = 1.40 ±0.06) compare with control group(P＜0. 01, P ＜ 0. 05). Immunohistochemistry showed similar results. Conclusion These data suggest that the neuroprotective effect of sertraline may play an important role in depression therapy, and this effect might be mediated by TH and pERK1/2 up-regulation.