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1.
AIM: To investigate whether chrysophanol alleviates amyloid β-protein (Aβ)-induced cognitive dysfunction and the underlying antioxidative mechanism.METHODS:Adult male Wistar rats (230~250 g) were randomly divided into control group, Aβ1-42 group, chrysophanol group, and Aβ1-42+chrysophanol (1, 10 and 100 mg/kg) groups. Aβ1-42 was delivered by intracerebroventricular injection under the guidence of a brain stereotaxic apparatus. Y-maze test, open-field test and Morris water maze test were performed 1 week after Aβ1-42 injection to evaluate the ability of rat spacial learning and memory. Chrysophanol was intraperitoneally injected once daily for 5 consecutive days. After the behavioral tests, the animals were sacrificed immediately by decapitation, and the hippocampus were collected. The malondialdehyde (MDA) content and the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) in the hippocampus were measured.RESULTS:Multiple (7 consecutive days, once daily) but not single (once a day) chrysophanol treatment at 1, 10 and 100 mg/kg effectively prevented Aβ1-42-induced cognitive function deficits in a dose-dependent manner as shown by Y-maze test and Morris water maze test. Moreover, the Aβ1-42-induced increase in MDA content and decrease in the activity of antioxidant enzymes (SOD, GSH-Px and CAT) in the hippocampus of the rats were also attenuated by multiple chrysophanol treatment.CONCLUSION:Repeated chrysophanol treatment attenuates Aβ1-42-induced cognitive deficits and synaptic plasticity dysfunction, and the mechanisms underlying the neuroprotective effects are likely due to its antioxidant activity.  相似文献   

2.
AIM：To investigate the effect of insulin signaling on the development of Alzheimer disease (AD) and to explore its potential mechanisms. METHODS：The rats were treated with streptozotocin (STZ, 3 mg/kg) intracerebroventricularly (ICV) at the 1st day and the 3rd day of the experiment to induce dementia model. Twenty-one days after the injection of STZ at the 1st day, spatial learning and memory of the rats were determined by Morris water maze test. The expression levels of insulin-degrading enzyme (IDE), glycogen synthase kinase 3β (GSK-3β), phosphorylated GSK-3β (p-GSK-3β), tau and phosphorylated tau (p-tau) were measured by Western blotting. The levels of amyloid β-proteins (Aβ1-40 and Aβ1-42) in the brain of the rats were detected by the method of immunohistochemistry. The mRNA levels of insulin, insulin receptor, tau and IDE were measured by real-time RT-PCR. RESULTS：ICV-STZ deteriorated the abilities of spatial learning and memory of the rats and reduced the activity of IDE and the mRNA levels of insulin and insulin receptor. STZ treatment enhanced GSK-3β activity and tau phosphorylation. The levels of Aβ1-40 and Aβ1-42 in cerebral cortex were significantly increased in the rats treated with STZ. CONCLUSION：ICV-STZ results in AD-like behaviors and pathological changes via damaging the brain insulin signaling, indicating that insulin signaling may play important roles in the AD pathogenesis.  相似文献   

3.
AIM:To explore the effect of TAK-242 on the learning and memory ability of C57BL/6 mice with sepsis-associated encephalopathy induced by lipopolysaccharide (LPS), to observe the pathological and morphological changes of the mouse brain, and to explore the mechanism of protein pathway associated with the effect of TAK-242. METHODS:Healthy female C57BL/6 mice (n=80), aged 10~12 months, weighing 20~30 g, were randomly divided into 4 groups (n=20):blank control (CON) group, TAK-242 control (TAK) group, sepsis encephalopathy model (LPS) group and TAK-242 pretreatment (T+L) group. Peripheral inflammation in the mice was detected by testing the arterial blood and lung tissues. The behavioral changes of the mice were observed by the open-field test, elevated plus-maze test (EPMT) and Morris water maze test. Immunohistochemistry was performed to observe the changes of microglia-specific marker, ionized calcium-binding adapter molecule-1 (Iba-1), in the hippocampus. Finally, the protein expression levels of NF-κB p65, TLR4, Aβ1-42 and p-tau (S396) were determined by Western blot. RESULTS:Compared with CON group, the mice in other groups didn't showed significant difference in the arterial blood gas analysis and lung tissue HE staining. In the anxiety and fear behavior tests, central active duration and times of crossing central field of the mice in LPS group were significantly decreased compared with CON group (P<0.01). The times of open arm entry and the times of head area entry in the EPMT were significantly less than those in CON group (P<0.05). The escape latency of spatial probe experiments was significantly extended (P<0.05). Microglial activation in the hippocampus was significantly increased (P<0.05) and the protein expression levels of NF-κB p65, TLR4, Aβ1-42 and p-tau (S396) were significantly increased (P<0.01). Conversely, compared with LPS group, the central active duration and times of crossing central field in T+L group were significantly increased (P<0.01). The times of open arm entry and the times of head area entry in the EPMT were significantly increased (P<0.05). The escape latency of spatial probe experiments was significantly shortened (P<0.05). Microglial activation in the hippocampus was significantly decreased and the protein expression levels of NF-κB p65, TLR4, Aβ1-42 and p-tau (S396) were down-regulated (P<0.05). CONCLUSION:TAK-242 obviously improves the ability of learning and memory, and the mechanism may be related to the inhibition of the central microglia activation and down-regulation of protein expression levels of NF-κB p65, TLR4, Aβ1-42 and p-tau (S396).  相似文献   

4.
AIM: To investigate the relationship between classical Wnt pathway with β-amyloid peptide(Aβ) deposition in hippocampus of insulin resistance(IR) rat model and to observe the above-mentioned proteins and the correlation with peroxisome proliferator-activated receptor γ(PPARγ) by treating the IR rats with rosiglitazone.METHODS: The rat models of IR and TZD were made. The plasma insulin and the plasma glucose levels were tested by RIA and glucose-oxidase methods, respectively. The indexes of insulin resistance were calculated by HOMA-IR. The proteins of Aβ, Wnt3a, β-catenin and PPARγ were analyzed by Western blotting.RESULTS: The plasma insulin in IR group was significantly higher than that in control group. Insulin resistance, which was calculated by HOMA-IR, was significantly higher in IR group than that in control group. The levels of Aβ and β-catenin in IR group were higher than those in control group, while the levels of Wnt3a and PPARγ were decreased. After treatment with rosiglitazone, Aβ was reduced but Wnt3a, β-catenin and PPARγ were increased.CONCLUSION: In hippocampus of IR rats, Aβ is deposited and the levels of Wnt3a and Wnt are reduced. Rosiglitazone, as a PPARγ agonist, can upregulate the activity of Wnt pathway and reduce Aβ deposition in rat hippocampus.  相似文献   

5.
AIM: To explore the effect of ovariectomization on Alzheimer-like phosphorylation of Tau in hippocampus of Sorague-Dawlery rats. METHODS: An animal model was developed using ovariectimized (OVX) rats, and the phosphorylation of Tau protein was measured by Western blot. RESULTS: The levels of phosphorylated Tau at PHF-1epitope were elevated in ovariectimized rat brain hippocampus 4 weeks and 8 weeks after ovariectomization, when compared with sham-OVX rats (P<0.05). On the other hand, the levels of non-phosphorylated Tau at Tau-1site were decreased in same brain regions at the same time point examined (P<0.05). No significant difference of phosphorylated Tau at those epitops was seen 1 week, 2 weeks, 3 weeks after ovariectomization between sham-OVX group and OVX group (P>0.05). CONCLUSION: Ovariectomization may induce Alzheimer-like hyperphosphorylation of Tau protein in brain hippocampus of rats.  相似文献   

6.
AIM:To investigate the effect of tenuigenin(TEN) on hyperphosphorylation of tau protein in neurons of amyloid β-peptide1-40(Aβ1-40) -induced Alzheimer disease(AD) rats. METHODS:Aβ1-40 was injected into hippocampus CA1 region of the rats to establish AD model. TEN at different doses(18.5 mg/kg, 37.0 mg/kg and 74.0 mg/kg) was intragastrically administered. The protein expression of protein kinase A(PKA),protein phosphatase 2A(PP2A), total tau and p-tau(Ser396) in the neurons was observed by the method of immunohistochemistry. The protein content of total tau and p-tau(Ser396), and the expression level of PKA and PP-2A were detected by Western blotting analysis. RESULTS:In Aβ1-40 group, the level of total tau, the phosphorylation of tau protein and the expression of PKA were significantly increased compared with those in sham operation group. Meanwhile, the expression of PP2A in Aβ1-40 group was lower than that in sham operation group. In TEN treatment group, the level of total tau, the phosphorylation of tau protein and the expression of PKA were markedly decreased, and the expression of PP2A was increased as compared with Aβ1-40 group. CONCLUSION:TEN may protect the neurons from the toxic effect of Aβ1-40 and reduce the hyperphosphorylation of tau(Ser396) in the neurons of AD rats by activating the expression of PP2A and inhibiting the expression of PKA.  相似文献   

7.
YAN Can  WU Li-li  XU Zhi-wei  SHI Ya-fei  PAN Yi 《园艺学报》2005,21(10):2032-2034
AIM: To observe the effect of Jiawei sinisan (JWSNS) on some amino acids in hippocampus of rats with chronic stress. METHODS: Wistar rats were randomly divided into 3 groups: control, model and JWSNS group. OPA (HPLC) was adopted to detect the contents of amino acids in hippocampus. RESULTS: The contents of Glu and Asp in hippocampus of model group increased significantly (P<0.01), while the contents of GABA and Tau decreased significantly (P<0.01 or P＜0.05). In JWSNS group, the contents of Glu and Asp decreased significantly, although GABA and Tau was no significant difference compared with the chronic stress group. CONCLUSION: JWSNS regulates the levels of amino acids in hippocampus during chronic stress, which prevents the neuro-toxicity of excitatory amino acids.  相似文献   

8.
AIM: To investigate the effect of high mobility group box-1 protein (HMGB1) on the expression of nuclear factor-κB (NF-κB) in BV-2 cells stimulated with amyloid β-protein (Aβ)25-35. METHODS: Cultured BV-2 cells in logarithmic growth phase were divided into 4 groups:normal cell group (without any treatment), model group (treated with Aβ25-35 at 40 μmol/L), RNA interference (RNAi) group (conducted with HMGB1-siRNA followed by Aβ25-35 stimulation) and solvent control group (treated with 0.1% DMSO). After treatment with Aβ25-35 for 24 h, the protein levels of HMGB1 and NF-κB in BV-2 cells were determined by Western blot. RESULTS: Aβ25-35 at 40 μmol/L was used to stimulate BV-2 cells. The GFP fluorescence-tagged HMGB1-siRNA (30 nmol/L) was used to transfect BV-2 cells and its transfection efficiency was about 80%~90%. The results of Western blot showed that the protein level of HMGB1 was significantly decreased after the interference of siRNA fragment (P<0.05). The protein levels of HMGB1 and nucleic NF-κB p65 were dramatically increased in BV-2 cells stimulated with Aβ25-35 (P<0.05). After RNA interference with HMGB1, the expression of HMGB1 and nucleic NF-κB p65 were significantly decreased in BV-2 cells stimulated with Aβ25-35 (P<0.05). CONCLUSION: RNA interference with HMGB1 reduces the expression of nucleic NF-κB in BV-2 cells stimulated with Aβ25-35.  相似文献   

9.
LIU Han  LUO Yong-jie 《园艺学报》2018,34(10):1805-1810
AIM: To investigate the effect of edaravone on acute cerebral ischemia/reperfusion rats. METHODS: SD rats were randomly divided into sham operation group (saline), model group (modeling given saline), low dose group (edaravone at 6 mg/kg) and high dose group (edaravone at 10 mg/kg). The rat model was established by Zea Longa suture method. The nerve function scores were evaluated after operation, and the infarct volume was measured by TTC assay. The mRNA expression of aquaporin 4 (AQP4) and amyloid β-protein (Aβ) in the brain tissue was detected by RT-qPCR. The protein levels of APQ4 and Aβ were determined by Western blot. The activity of matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9(MMP9) was detected by gelatin zymography. RESULTS: Compared with model group, edaravone administration markedly alleviated neurological deficits, histological damages and brain edema. The mRNA and protein levels of AQP4 and Aβ, and the activity of MMP2 and MMP9 were downregulated (P<0.05). Furthermore, the improvements in high dose group were significantly more effective than those in low dose group. CONCLUSION: Edaravone significantly reduces neurological deficits and brain edema in the rats with acute ischemic stroke, and the mechanisms may be related to the downregulation of AQP4 and Aβ, and the activation of MMP2 and MMP9.  相似文献   

10.
AIM: To investigate the effect of bone marrow mesenchymal stem cell (BMSC) transplantation on learning and memory abilities and pathological changes of Alzheimer disease (AD) mice and the molecular mechanisms. METHODS: C57/BL6 wild-type (WT) and transgenic (Tg) mice were randomly divided into 4 groups:WT/PBS group, WT/BMSCs group, Tg/PBS group and Tg/BMSCs group. The mice were administered with PBS or BMSCs via intracerebroventricular injection. Spatial learning and memory abilities of the mice were evaluated by Morris water maze test on the 3rd day after surgery. Real-time PCR was applied to detect the mRNA expression of CX3C chemokine ligand 1 (CX3CL1), CX3C chemokine receptor 1 (CX3CR1), IL-1β, TNF-α, Nurr1, YM1, insulin-degrading enzyme (IDE) and matrix metalloproteinase 9 (MMP9). The protein levels of CX3CL1 and Aβ42 were measured by ELISA. Western blot was used to detect the protein expression of postsynaptic density protein 95 (PSD95) and synaptophysin (SYP). RESULTS: The transplanted BMSCs were observed near the hippocampus of APP/PS1 mice on the 10th postoperative day. The escape latency of the mice in Tg/PBS group was significantly longer than that in the WT/PBS mice (P<0.05). Compared with Tg/PBS group, the escape latency of Tg/BMSCs group was significantly shorter (P<0.05), and the mRNA and protein levels of CX3CL1 in Tg/BMSCs group were significantly higher than those in Tg/PBS group (P<0.01). The results of immunohistofluorescence staining showed that BMSC transplantation promoted the activation of microglia in the brain of WT and Tg mice. The mRNA expression of YM1 was up-regulated in WT/BMSCs group and Tg/BMSCs group (P<0.05). Compared with WT/PBS mice, the mRNA expression of TNF-α in the cortex and hippocampus of Tg/PBS group was significantly increased (P<0.05), and the mRNA expression of Nurr1 in the cortex was significantly decreased (P<0.01). Meanwhile, the mRNA expression of TNF-α in the cortex of Tg/BMSCs mice was decreased (P<0.01) and the mRNA expression of CX3CR1 and Nurr1 was up-regulated compared with Tg/PBS group (P<0.05). The results of Western blot showed that the protein levels of PSD95, p85, p110 and p-Akt in Tg/BMSCs group were significantly higher than those in Tg/PBS group (P<0.05). Finally, BMSC transplantation reduced the protein level of Aβ42 in APP/PS1 mice (P<0.05), and increased the mRNA expression of IDE and MMP9 in the hippocampus (P<0.05). CONCLUSION: BMSC transplantation modulates neuroinflammatory responses and promotes neuroprotective factor and synaptic protein expression, thus improving the learning and memory abilities in the APP/PS1 mice, which may be achieved by up-regulating the expression of CX3CL1.  相似文献   

11.
AIM: To explore the therapeutic effect of a novel Rho kinase inhibitor FSD-C10 on β-amyloid protein precursor (APP)/presenilin-1 (PS1) double transgenic mice. METHODS: The transgenic mice overexpressing human APP with the Swedish mutation (695) and human PS1 with ΔE9 mutation at the age of 8 months were used in this study. The mice were randomly divided into model group and FSD-C10 intervention group, and wild-type mice at the same age served as normal controls. The mice in FSD-C10 intervention group were treated with FSD-C10 (25 mg·kg-1·d-1) for 2 months by intraperitoneal injection. The mice in model group and the wild-type mice were injected with saline in the similar manner. Morris water maze (MWM) test was applied to examine the capacity of learning and memory. The Aβ1-42 deposition, Tau protein phosphorylation, and the expression of β-site APP-cleaving enzyme (BACE) as well as inflammatory molecules, such as TLR-4 and NF-κB, and M1/M2 microglial markers, such as iNOS and Arg-1, were determined by the methods of immunohistochemistry and Western blot. RESULTS: Compared with model group, FSD-C10 significantly improved the learning and memory abilities of APP/PS1 double transgenic mice, accompanied by reduced Aβ1-42 deposition, Tau protein phosphorylation and BACE expression in the hippocampus. The intervention of FSD-C10 decreased the protein levels of TLR-4 and p-NF-κB, reduced the expression of iNOS and increased the expression of Arg-1 in the brain tissues. CONCLUSION: The novel Rho kinase inhibitor FSD-C10 improves the capacity of spatial learning and memory in APP/PS1 double transgenic mice, which may be related to the inhibition of TLRs/NF-κB signaling pathway, the reduction of the secretion of inflammatory molecules and the polarization of anti-inflammatory M2 microglia, thus improving the inflammatory microenvironment of the brain in APP/PS1 double transgenic mice.  相似文献   

12.
AIM：To explore the anti-inflammatory effect of huperzine A (HupA) and its neuroprotective effect on rat neural stem cells (NSCs). METHODS：The microglia and NSCs were isolated from neonatal rat hippocampal tissues and co-cultured in a Transwell system. The cells were divided into 3 groups：control group, amyloid beta-peptide (Aβ) group and HupA group. The microglia layer in Aβ group was treated with Aβ1-42 (10 μmol/L), while that in HupA group was pretreated with HupA (1 μmol/L) before Aβ1-42 stimulation. The culture supernatant levels of inflammatory mediators, including interleukin 6 (IL-6), tumor necrosis factor α (TNF-α) and macrophage inflammatory protein 1α (MIP-1α), were detected by LiquiChip technique. The apoptosis of NSCs was determined by flow cytometry and Western blotting. RESULTS：The microglia secreted a large number of inflammatory mediators with the stimulation of Aβ. In Aβ group, the levels of IL-6, TNF-α and MIP-1α were significantly higher than those in control group at 72 h (P<0.01), and the apoptotic rate of NSCs was 25.46% (P<0.01). In HupA group, the concentrations of IL-6, TNF-α and MIP-1α decreased significantly as compared with Aβ group (P<0.01), and the apoptotic rate of NSCs was only 8.05% (P<0.01). The Bcl-2/Bax ratio in HupA group was higher than that in Aβ group (P<0.05). CONCLUSION：Huperzine A reduces the secretion of cytokines and chemokines, and attenuates microglia-mediated neuroinflammation, thus protecting NSCs against inflammation-induced apoptosis.  相似文献   

13.
AIM: To explore the effects of astragalan (AG) on the neurotransmitters,acetylcholine (ACh), norepinephrine (NE) and 5-hydroxytryptamine (5-HT), and the expression of c-fos mRNA in hippocampus after ischemic brain injury in rats. METHODS: Male Wistar rats (180~220 g) were randomly divided into 10 groups (n=10): sham-operated group (SOG), 3 model groups (MG 1 d, 3 d, 7 d) and 3 low- or high-dose AG treatment groups (L/H-AGTG 1 d, 3 d, 7 d), respectively. The middle cerebral artery of the rats in MG group and AGTG group were blocked by operation to induced brain injury. The cerebral blood vessels of the animals were blocked on day 1, day 2 and day 7, respectively, after the L/H-AGTG were treated with AG (5 mg/kg and 15 mg/kg, ip). The content of ACh,5-HT and NE was determined using their respective ELISA kits, and the expression of c-fos mRNA in the hippocampus homogenate was semiquantitative analyzed by RT-PCR after neurologic impairment (NIP) was scored. RESULTS: AG attenuated the injury in hippocampus by cerebral ischemia in a dose-dependent manner. The content of ACh, 5-HT and NE in L-AGTG 7 d,H-AGTG 3 d and 7 d groups was significantly higher than that in MG group, but was lower in SOG group (P<0.05 or P<0.01). The mRNA expression of c-fos in SOG group was lower than that in MG group (P<0.05 or P<0.01), indicating that reinforcement expression of c-fos mRNA by cerebral ischemia and the expression of downstream genes may be beneficial for protecting the neurons. The mRNA expression of c-fos in H-AGTG 3 d/7 d groups was higher than that in MG group (P<0.05). CONCLUSION: AG attenuates the damage of neurons and improves the functions of hippocampus under the condition of cerebral ischemia/reperfusion by increasing the content of ACh, NA and 5-HT, and the mRNA expression of c-fos in hippocampus.  相似文献   

14.
AIM: To observe the effects of neuroglobin(NGB) overexpression on the apoptosis induced by Aβ in the brains of double transgenic AD(APPswe/PS1dE9) mice and to explore its potential mechanisms.METHODS: Twenty-four 13-month-old double transgenic AD mice were randomly divided into 3 groups:intracerebroventricular injection with normal saline(NS) group, intracerebroventricular injection with pcDNA3.1 and NS group, and intracerebroventricular injection with pcDNA3.1 and pNGB group. Immunohistochemistry was used to detect the expression of Aβ1-42 in the brains. TUNEL staining was used for analyzing the apoptosis, and the protein levels of cleaved caspase-3, caspase-9, PI3K, Akt and p-Akt were determined by Western blot.RESULTS: After intracerebroventricular injection with pNGB, the areas of Aβ1-42 in the hippocampus and cortex were decreased compared with NS group and pcDNA3.1+NS group(P<0.01). The TUNEL-positive staining cells in the pNGB group were less than those in NS group and pcDNA3.1 group(P<0.01). NGB overexpression attenuated the protein levels of cleaved caspase-3 and caspase-9(P<0.01), but induced the production of PI3K and p-Akt(P<0.01).CONCLUSION: Overexpression of pNGB significantly inhibits the generation of Aβ and attenuates the apoptosis induced by Aβ, indicating that NGB overexpression activates PI3K/Akt pathway and inhibits the production of cleaved caspase-3 and caspase-9, which were tightly related with apoptosis.  相似文献   

15.
AIM: To study the effects of baicalin (BC) on glial fibrillary acidic protein (GFAP) and nuclear factor-κB (NF-κB) expression and neuronal apoptosis in juvenile rat hippocampus after status convulsion (SC). METHODS: One hundred and ninety five juvenile male Sprague-Dawley rats were randomly divided into 3 groups: normal saline pretreatment group (NS group), SC group and SC with BC pretreatment group (BC group). Each of these 3 groups would be subdivided into 5 subgroups sacrificed at 4 h, 12 h, 24 h, 48 h and 72 h after SC. The rat SC model was prepared by lithium-pilocarpine chemical method. The protein expression of GFAP and NF-κB was detected by the method of immunohistochemistry. The mRNA expression of GFAP was detected by RT-PCR. The neuronal apoptosis was observed by TdT-mediated dUTP nick end labeling (TUNEL). RESULTS: Compared with NS group, the GFAP positive cells was increased in SC group (P<0.05). Compared with SC group, the expression of GFAP was significantly reduced in BC group (P<0.05). Compared with NS group, the NF-κB positive cells was increased in SC group (P<0.05). Compared with SC group, the expression of NF-κB was significantly reduced in BC group. RT-PCR showed that the expression trend of GFAP mRNA was similar to that of the protein. Compared with NS group, the TUNEL positive cells in the hippocampus CA1 area in SC group increased significantly 12 h after SC (P<0.01), and reached a peak at 48 h. After the intervention with BC, the TUNEL positive cells decreased significantly between 12~48 h after SC (P<0.05 or P<0.01), but the number of TUNEL positive cells remained significantly greater than that in NS group (P<0.05). CONCLUSION: The expression of GFAP and NF-κB in the hippocampus increased after SC in rats. Baicalin decreases the expression of GFAP and NF-κB in hippocampus of rats with pilocarpine-induced seizures, and reduces the number of neuronal apoptosis, suggesting that baicalin may protect against the brain damage caused by status convulsion.  相似文献   

16.
AIM: To investigate the effects of Scutellaria barbata flavonoids (SBF) on neurofibrillary tangle (NFT) aggregation, tau protein phosphorylation and the regulated mechanism of glycogen synthase kinase (GSK) 3β and protein phosphatase (PP) 2A in the rats induced by amyloid β protein 25-35 (Aβ25-35) in combination with AlCl3 and recombinant human transforming growth factor (RHTGF)-β1(composited Aβ). METHODS: The male SD rats were used to establish the simulated Alzheimer disease (AD) model by intracerebroventricular injection of composited Aβ. The Morris water maze was applied for screening the successful model rats with learning and memory deficits. The successful model rats were daily and orally administrated with SBF at doses of 35, 70 and 140 mg/kg or positive control drug Ginkgo biloba leaves flavonoids (GLF) at 140 mg/kg for 37 d. The silver nitrate staining was used to determine the cortical NFT. The protein levels of total tau, phosphorylated protein of tau at Ser199 and Ser214 sites, GSK3β and PP2A in hippocampus and cortex were determined by Western blot. The mRNA expression of GSK3β and PP2A in the hippocampus and cortex was detected by RT-PCR. RESULTS: Compared with sham group, the cell number of positive NFT with silver nitrate staining in model rat cerebral cortex was significantly increased. The protein levels of phosphorylated tau protein at Ser199 and Ser214 sites, GSK3β in the hippocampus and cerebral cortex in the model rats dramatically elevated, and PP2A was marked decreased as compared with the sham group rats. Meanwhile, the mRNA expression of GSK-3β significantly increased but PP2A was decreased. However, these above abnormalities were differently attenuated by treating with SBF at different doses or GLF at 140 mg/kg for 37 d. CONCLUSION: SBF suppresses the NFT aggregation by inhibition of the regulatory functions of GSK-3β and PP2A, thus reducing the phosphorylation of tau protein.  相似文献   

17.
AIM: To study the role of P2Y1 receptor in the activation of astrocytes induced by Aβ25-35.METHODS: Astrocytes were isolated and cultured from newborn Wistar rats and divided into control group, Aβ25-35 group, MRS2179(P2Y1receptor inhibitor)+Aβ25-35 group and MRS2179 group by treating the cells with the corresponding reagents. The expression levels of GFAP and P2Y1 were determined by the methods of immunohistochemistry, immunofluorescence and Western blotting.RESULTS: No significant change of the astrocyte numbers in all groups was observed. Compared with the control cells, the fluorescence intensity of GFAP significantly increased in Aβ25-35 group and decreased in both MRS2179+Aβ25-35 group and MRS2179 group. The expression level of GFAP determined by Western blotting and immunofluorescence showed the similar trend of change in each group. Compared with control group, the expression of P2Y1 in Aβ25-35 group was significantly increased (P<0.05), and no significant change between MRS2179+Aβ25-35 group and MRS2179 group was found (P>0.05).CONCLUSION: Aβ25-35 activates astrocytes by activation of P2Y1 receptor.  相似文献   

18.
AIM: To investigate the effects of curcumin (Cur) on the expression of High mobility group box 1 protein (HMGB1), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) in amyloid-β (Aβ)-induced primary rat microglial cells. METHODS: Microglia were derived from the cerebral cortices of postnatal rat brains. The cells were identified by immunocytochemistry using mouse anti rat Iba-1 monoclonal antibody. A cell model using primary rat microglial cells incubated with Aβ25-35 as an inflammation model of Alzheimer's disease (AD) was set up. The morphological characters of primary rat microglial cells were observed. The concentration of Aβ25-35 and the treatment concentration of curcumin were selected by CCK-8 assay. Cultured primary rat microglial cells were divided into 5 groups:normal cell group, Aβ25-35 group, Cur group, Aβ25-35+Cur group and Aβ25-35+DMSO group. The expression of HMGB1, NF-κB, and receptor for advanced glycation end products (RAGE) was detected by Western blot. The levels of HMGB1, IL-1β, and TNF-α in the culture supernatant were measured by ELISA. RESULTS: The purity of primary microglias determined by Iba-1 immunofluorescence was more than 95%. The protein levels of HMGB1, RAGE and NF-κB were significantly increased after Aβ25-35 stimulation. After treatment with Cur, the protein levels of HMGB1, RAGE and NF-κB were significantly decreased (P<0.05). The levels of HMGB1, IL-1β and TNF-α in the supernatant were significantly increased after Aβ25-35 stimulation. Cur significantly decreased the level of HMGB1, IL-1β and TNF-α in the supernatant. CONCLUSION: Curcumin significantly inhibits neuroinflammation stimulated by Aβ25-35 in primary rat microglial cells.  相似文献   

19.
AIM: To investigate the effects of Chinese traditional medicine-selected recipe Q0409 on the ability of learning and memory in SAM-P/8 mice. METHODS: Total 91 mice (4-month-old SAM-P/8 mice, SAM-R/1 mice and Kunming mice) were used in the study, in which the male and female animals were labeled separately. According to the performance of Morris water maze test, the mice were divided into 5 groups randomly. The mice were fed with different drugs or distilled water for 60 d (from 4 months to 6 months). The mice were fed with the drugs from 61 d to 65 d, and 1 h later each time, the Morris water maze test was carried out. After this Morris test were finished at 65 d, the mice were killed immediately and their hippocampal tissues were isolated. Half of the hippocampal tissues were added with precooled normal saline and made into 10% (g/mL) homogenate for detecting the protein content and acetyl cholinesterase (AChE) activity. The other half was fixed with 4% paraformaldehyde and embedded with paraffin for immunohistochemical staining of amyloid β-protein (Aβ). RESULTS: Compared with model group, the results of navigation training and spatial probe training in Morris water maze test were significantly improved (P<0.05), and the activity of AChE in the hippocampal homogenate was significantly decreased (P<0.05) in Q0409 treatment group. No difference in Q0409 group was observed compared with control group and positive drug (huperzine A) group. Immunohistochemical staining showed no typical "senile plaques" in the male mice of Q0409 group, while there was shallower and smaller brown staining in the hippocampus of the female mice of Q0409 group. The positive area of Aβ deposition decreased in the CA1 area of hippocampal tissues in Q0409 group. These results were similar to those in positive drug group. CONCLUSION: Q0409 improves the ability of learning and memory in SAM-P/8 mice, which is related to the inhibition of AChE activity and the reduction of Aβ protein deposition in the hippocampus. The effects is similar to those of huperzine A.  相似文献   

20.
AIM: To investigate the effects of rolipram on the ability of learning and memory and the activity of PDE4 in hippocampus following the focal brain injury induced by ischemia- reperfusion in rats. METHODS: The cerebral ischemia-reperfusion injury model was made by middle cerebral artery occlusion (MCAO) in rats. The rats were randomly divided into sham-operated group, model group, and rolipram group. Rolipram was administered once a day (1 mg/kg, ip) from 6 h after the onset of the operation for 2 weeks. Then the learning and memory abilities were tested after Morris water maze and step-though training. The activity of PDE4 in hippocampus was evaluated by HPLC. RESULTS: In the Morris water maze test, compared to sham-operated group, the platform-finding time and swimming distance in model group were significantly longer (P<0.05). Compared to model group, the platform-finding time and swimming distance in rolipram group were significantly shorter (P<0.05). In the step-through test, compared to sham-operated group, the lantent period in model group was significantly shorter (P<0.01) and the error times were statistically increased(P<0.05). Compared with model group, the lantent period in rolipram group were significantly longer (P<0.05), and the error times were markedly decreased. The assay of the HPLC demonstrated that the activities of PDE4 in hippocampus in model group were higher than those in the sham-operated group and rolipram group. CONCLUSION: Rolipram reduces the activity of PDE4 in hippocampus and enhances the ability of learning and memory after the injury induced by ischemia-reperfusion.  相似文献   

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