ABSTRACT
Objective To investigate the correlationship between depressed behaviors and interleukin-1β (IL-1β) in brain tissue in mice which are insensitive to fluoxetine,and to mimic the treatment resistant depression (TRD) in clinical condition.Methods 50 BALB/c mice were randomly divided into Control group (Control),Chronic unpredictable mild stress (CUMS) group and CUMS+fluoxetine group.Mice in Control group were raised ad libitum for 9 weeks,those in CUMS group received CUMS for 9 weeks and those in CUMS+fluoxetine group received 8 weeks' CUMS followed 1 week' s treatment with Fluoxetine(10 mg · kg-1 · d-1).At the end of the 9th week,mice in(CUMS + treatment)group were selected into antidepressant treatment-resistant mice(ATRM) as no remission and Depression Group (DM) as symptoms improved.Body mass test (BMT),open field test (OFT) and forces swim test (FST) were completed respectively in these 4 groups at the endpoint of the experiment,and the brain tissue were extracted after the tests for IL-1β Elisa test.Results (1) BMT:there was no effect of weightgain in ATRM after 1 week' s therapy with Fluoxetine.There was no difference in body-weight between ATRM ((18.56±7.56) g) and CUMS ((19.03± 8.58) g) mice,while compared with Control ((24.56±5.45) g) and DM mice ((20.12±9.17) g) ATRM and CUMS mile's body weight were significantly lower (P＜0.05).(2)OFT and FST:in OFT,there was no significant difference in of horizontal moving distance(F=0.355) either in the frequencies of entering the central zone (F=0.327) among the 4 groups;in OFT,the immobility time of ATRM ((241.50 ± ± 36.55) s) was significantly longer than that in DM ((156.00± 25.47) s) (F=13.573,P＜0.05).(3) Elisa test of IL-1β:the brain' s IL-1β serum level in ATRM ((164.90±46.70) pg/mg) was higher than those in Control ((69.68±6.56) pg/mg)),and DM ((93.09±4.65) pg/mg) (P＜0.01),while no difference with that in CUMS mice.Additionally,the depressive behaviors in ATRM showed its positive correlation with the IL-1β level in CNS (r=0.669,P=0.006).Conclusion CUMS can elicit the refractory depressive symptoms in BALB/c mice to simulate TRD' s characteristic,and the elevated level of IL-1 β within brain tissue may play an important role in the development of TRD.
ABSTRACT
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.
ABSTRACT
BACKGROUND:Osteoporosis is a bone metabolic disease that affects women more than men. Prevention and treatment of osteoporosis is becoming a serious medical problem because of the aging of the population. OBJECTIVE:To explore the effects of lithium chloride treatment on bone microarchitecture and bone marrow stromal cel differentiation of ovariectomized osteoporosis rats. METHODS:After ovariectomy, 28 of 30 healthy female Sprague-Dawley rats, 3 months old, were randomly divided into the folowing three groups: ovariectomizedin vivo group (9 rats), ovariectomizedin vitro group (10 rats), and lithium chloride group (9 rats). At the 11th week postoperatively, rats in the lithium chloride were intragastricaly injected with lithium chloride at a dose of 15 mg/kg, three times per week. After 8 weeks of treatment, the bone microarchitectures of the rat left femur in the ovariectomizedin vivo group and lithium chloride group were detected by micro-CT. The bone marrow mesenchymal stem cels were freshly isolated from the bone marrow of the bilateral femurs and tibia of rats in the ovariectomizedin vitro group. After 24 hours of inoculation, the cels were cultured in lithium chloride and divided into 0 mmol/L (control), 1 mmol/L and 5 mmol/L groups. At 6 and 8 days of culture, the medium was changed and lithium chloride with the corresponding concentrations was added. At 10 days of culture, western blot assay was adopted to detect protein expression of Runx-2, SP7 and PPARγ2. RESULTS AND CONCLUSION:(1) Compared with the ovariectomizedin vivo group, the volume density of trabecular bone, number of trabecular bone, and bone volume fraction in the lithium chloride group were significantly increased and the separation of trabecular bone was significantly decreased. However, no differences were seen in the thickness of trabecular bone and structure model index. (2) Lithium chloride at 1 and 5 mmol/L could increase the protein expression of Sp7 and Runx-2 in bone marrow stromal cels, but decrease the protein expression ofPPARγ2. These results indicate that lithium chloride may improve the microarchitecture of the trabeculr bone in ovariectomized osteoporosis rats through stimulating the osteogenic differentiation of bone marrow stromal cels.
ABSTRACT
Objective To investigate the effect of repetitive transcranial magnetic stimulation (rTMS) on the depressive like behaviors and expression of brain derived neurotrophic factor (BDNF),IL-1β and NF-κB of hippocampal in chronic unpredictable mild stress (CUMS) rats.Methods Thirty-two adult male rats were randomly divided into four groups (n =8):Control group,Control + rTMS group,CUMS group and CUMS + rTMS group.The sucrose preference test,forced swim test and open field test were used to evaluate depressive like behaviors for each groups.In addition,the expression of BDNF,NF-κB and IL-1 β in hippocampal were detected by western blot and ELISA after behavioral test,respectively.Results 1.The effects of rTMS on depressive like behaviors of CUMS rats:in the sucrose preference test,the sucrose preference rate of CUMS rats (0.67 ± 0.06) was significantly lower than Control group (0.91 ± 0.04),which was higher in the CUMS + rTMS group (0.83 ±0.08).In the forced swim test,the immobility time of CUMS group ((26.88 ± 11.33) s) was longer than Control group ((15.22 ± 6.75) s) and CUMS + rTMS group ((18.41 ± 6.95) s).In the open field test,both the total distance travelled and number of central area entry times of CUMS group((849.165 ± 769.01) cm,(7.42 ± 5.68))were significantly shorter ((6224.81 ± 1403.2) cm) and smaller (22.86 ± 3.72) than Control group,and those of the CUMS + rTMS were longer ((4105.57 ± 1516.92)cm) and larger (21.25 ± 3.45).All the behavioral results were statistically significant (P＜ 0.05).And of all the aforementioned behavioral parameters,there were no significant differences between Control group and Control + rTMS group(P＞0.05).2.The effects of rTMS on the hippocampal expressions of BDNF,NF-κB and IL-1β in CUMS rats:compared with Control group,the hippocampal expression of BDNF in CUMS rats was significantly decreased,while the expressions of NF-κB and IL-1β in the hippocampus were significantly increased (P＜ 0.05).Compared with CUMS group,the hippocampa expression of BD-NF in the CUMS + rTMS group was increased,and the expressions of NF-κB and IL-1β in the hippocampus was significantly decreased (P ＜ 0.05).The expressions of BDNF,NF-κB and IL-1β had no differences between Control group and Control + rTMS group.Conclusion rTMS increased the expression of BDNF,reduced the production of NF-κB and IL-1β,and alleviated depressive like behaviors in CUMS rats.
ABSTRACT
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.