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Objective To investigate the effect of venlafaxine on learning and memory ability in rats with vascular dementia(VD).Methods Totally 90 Wistar rats were divided into sham-operation group,model group and treatment group (n=30 for each).The VD rat model was established by modified pulsinellis 4-vessel occlusion (4 VO).Rats in the sham-operation group and model group were administered with gastric perfusion of distilled water.Rats in the treatment group were administrated with gastric perfusion of Venlafaxine at 15 mg/kg per day for 4 weeks from the 2nd day after the modeling.The one-way avoidance test was performed to study the learning-memory ability of each group.The contents of norepinephrine,5-hydroxytryptamine and BDNF in the hippocampus and cortex of rats were observed.Results Model group demonstrated a decrease in the percentage of one-way avoidance test (50.3±6.2 vs.92.3±5.6,P＜0.01) as compared with sham-operation group,and this value was increased in treatment group (62 2±4.6).Compared with the sham-operation group,the contents of NE and 5-HT in the hippocampus [(226±34) pg/g and (340±40) pg/g],and cortex [(601±66) pg/g and (657±43) pg/g] in rat brains of model group were decreased (P＜0.01),while increased in treatment group [(264±45) pg/g and (379±42)pg/g,(665±68) pg/g and (798±51)pg/g,P＜0.05].The OD value of BDNF in the hippocampus (0.495±0.041) and cortex (0.488±0.042) were increased (P＜0.05) in model group,and in treatment group,BDNF levels were more higher (0.579±0.044 and 0.578±0.06/4,P＜0.05).Conclusions The content of brain monoamine neurotransmitters are decreased in rats with VD,while venlafaxine can improve the learning memory ability in model rats through increasing the levels of 5-HT,NE and BDNF in hippocampus and cortex.
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Objective To explore the possible molecular mechanism of Ginsenoside Rg1 preventing against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced substantia nigra neurons apoptosis in Parkinson disease(PD) mouse model. Methods C57BL mice were administrated(sc) with MPTP to produce PD mouse model.Different doses of Rg1(5.0,10.0,20.0*!mg/kg) were given(ip) prior 3*!d to MPTP in the pretreatment groups.Nissl staining,tyrosinehydroxythase(TH) immunostatining,cleaved caspase-3 immunostatining and TUNEL staining were used to observe the changes of nigra neurons,meanwhile,Western blot was used to detect the phosphorylated protein of JNK and c-Jun in substantia nigra. Results Pretreatment with Rg1 could prevent the loss of Nissl staining neurons and TH-positive neurons,inhibit JNK and c-Jun phosphorylation in SN,decrease the percent of cleaved caspase-3 and TUNEL-positive cell.Conclusion Rg1 can attenuate MPTP-induced apoptosis in substantia nigra neurons through blocking JNK signaling cascade.
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AIM: To study the possible molecular mechanism of beta-amyloid peptide_ 1-40 -induced apoptosis in rat cortical neurons. METHODS: 40 mg/L beta-amyloid peptide_ 1-40 (A?_ 1-40 ) was used to induce apoptosis in cultured rat cortical neurons. The level of CDK4, phosphorylated pRB were detected by flow cytometry and immunoblotting; RT-PCR was used to examine the mRNA expression of E2F1 while fluorescent spectrofluorometer was used to measure caspase-3 activity. All of the above study was designed to observe whether the level of CDK4, phosphorylated pRB and E2F1 mRNA expression could be affected by A?_ 1-40 . RESULTS: (1)The level of CDK4, phosphorylated pRB increased markedly 2-4 hours after treatment with A?_ 1-40 , and caspase-3 activity elevated remarkably 12-24 hours after treatment with A?_ 1-40 ; (2) E2F1 mRNA expression was upregulated 3 hours after incubation with A?_ 1-40 . CONCLUSION: A?_ 1-40 may induce apoptosis in rat cortical neurons in a manner dependent on CDK4-pRB-E2F1 pathway.
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AIM: To explore the possible signal transduction pathway of 1-methyl-4-phenylpyridinium(MPP +)-induced apoptosis. METHODS: The apoptosis of SHSY5Y cells induced by MPP + was observed by acridine orange-ethidium bromide(AO-EB) staining. Western blot was used to detect the activity of JNK in SHSY5Y cells, and the antisense oligo- neucleutide of JNK were used as inhibitor of JNK. RESULTS: MPP + induced apoptosis in SHSY5Y cells. During the apoptotic process, JNK activity increased. MPP +-induced apoptosis in SHSY5Y cells was obviously inhibited by pretreatment with NAC or by transfection with antisense oligonucleotide of JNK into SHSY5Y cells. Simultaneously, decrease in JNK activity and percentage of positive cleaved caspase-3 cells in these groups were also observed. CONCLUSION: The possible signal transduction pathway of MPP +-induced apoptosis in SHSY5Y cells might be attributed to the production of ROS ,activation of JNK and then activation of caspase 3.
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Objective To investigate the effects of caspase\|3 on ? ?? 1 40 induced apoptosis in rat cortical neurons. Methods Apoptosis was induced by 40?mg\5L -1 ?\|AP 1 40 .The apoptotic neurons were observed by TUNEL staining and DNA gel electrophoresis.The activity and mRNA expression of caspase\|3 was measured by fluorescent spectrofluorometer and RT\|PCR.The cleaved caspase\|3 was detected with immunocytochemistry. Results After treatment with ?\|AP 1\|40 ,the rat cortical neurons showed DNA fragmentation.The expression of caspase\|3 mRNA ratio to ? actin was 0^78,0^85 and 0^39 respectively after treatment for 12,24 and 48?h.Caspase\|3 activity was 133 24?7 47,192 16?11 03,88 87?4 24 MFI\5?g protein -1 \5h -1 .The cleaved caspase\|3 was observed within cytoplasm.Specific inhibitor of caspase\|3 Ac\|DEVD\|CHO inhibited caspase\|3 activation and blocked cortical neurons apoptosis markedly.Conclusion\ Caspase\|3 might be an executor during ? AP 1 40 induced apoptosis in rat cortical neurons.[