Effect of curcumin on scopolamine-induced memory impairment in mice

AIM:Scopolamine blocks cholinergic transmission and impairs learning and memory in mice. The purpose of this study was to evaluate the memory-improving properties of curcumin on scopolamine-induced memory impairment in mice. METHODS:The mice of memory impairment were induced by scopolamine. Step down test and Morris water maze test were used to observe the learning and memory ability in curcumin-treated mice. Biochemical assessments of AChE, MDA, and GSH-Px levels in brains were performed. RESULTS:Oral administration of curcumin significantly reduced the numbers of step-down errors (P<0.05) and prolonged the step-down latency induced by scopolamine (P<0.05). The escape latency time in mice treated with curcumin was remarkably reduced compared to that in scopolamine group by Morris water maze test (P<0.05). After the platform was removed, the total time that the mice swam in the target quadrant was also longer in curcumin group than that in model group (P<0.05). The data also indicated that curcumin significantly inhibited AChE activity (P<0.01) and prevented oxidative stress characterized by the significant reduction in MDA content and the significant increase in GSH-Px activities in the brain (P<0.01). CONCLUSION:Curcumin induces cognitive improvement by enhancing the function of cholinergic system and its antioxidant activity.     

Effects of Chinese traditional medicine-selected recipe Q0409 on ability of learning and memory in SAM-P/8 mice

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.     

Effect of BDNF expression in cerebral cortex and hippocampus on ability of learning and memory in APP/PS1 transgenic mice

AIM: To investigate the expression changes of brain-derived neurotrophic factor (BDNF) in the cerebral cortex and hippocampus and their effects on the ability of learning and memory in the wild-type (WT) mice and APP/PS1 transgenic mice. METHODS: WT mice and APP/PS1 transgenic mice were selected as study subjects. Aβ plaques, apoptosis rate and BDNF expression in the cerebral cortex and hippocampus of WT mice and APP/PS1 transgenic mice were detected by the methods of Congo red staining, TUNEL, immunofluorescence and Western blot. The abilities of learning and memory were determined by Morris water maze test. RESULTS: The Aβ plaques appeared in the cerebral cortex and hippocampus of APP/PS1 transgenic mice, and the number of Aβ plaques in 12-month-old mice was larger than that in 6-month-old mice (P<0.05). The number of apoptotic neurons in the cerebral cortex and hippocampus of 12-month-old APP/PS1 transgenic mice was larger than that of WT mice (P<0.01). The expression level of BDNF in the cerebral cortex and hippocampus of WT mice was higher than that of APP/PS1 transgenic mice (P<0.01). The Morris water maze test showed that the escape latency in APP/PS1 transgenic mice was longer than that in WT mice, and the times across the platform quadrant in 60 s was less than that in WT mice (P<0.01). The swim-tracking path of APP/PS1 transgenic mice was disordered and irregular. CONCLUSION: The expression of BDNF in the cerebral cortex and hippocampus of APP/PS1 transgenic mice was lower than that of WT mice, accompanied by increased neuronal apoptosis and decreased spatial learning and memory ability. The decrease in learning and memory ability may be related to decreased BDNF expression in the cerebral cortex and hippocampus of APP/PS1 transgenic mice, leading to increased neuronal apoptosis, which may be one of the pathological mechanisms of Alzheimer disease.     

Effects of Chinese herbal compound Huannaoyicongfang on inflammatory cytokines and oxidative stress in brain of APP transgenic mice

AIM: To study the effects of Chinese herbal compound Huannaoyicongfang (HNYCF) on inflammatory reaction and oxidative stress in the brain of Alzheimers disease (AD) animal model, and to explore its role in treating AD. METHODS: APP695V717I transgenic mice (3 months old),as an AD model in this study, were randomly divided into model group, donepezil group, HNYCF high-dose group and HNYCF low-dose group. C57BL/6J mice, which were of the same age and genetic background as the transgenic mice, were used as controls. The animals were administered intragastrically with the drug or water from 3 months old to 9 months old. Morris water maze test was performed to measure the spatial learning and memory ability. Step-down test was performed to observe the learning and memory ability of single passive avoidance response. The expression of nuclear factor kappa B (NF-κB) and peroxisome proliferator-activated receptor γ (PPARγ) in hippocampus CA1 region was detected by immunohistochemistry with image analysis. The levels of interleukin-6 (IL-6) and high sensitivity C-reactive protein (hs-CRP) in the brain cortex and hippocampus homogenate were measured by radioimmunoassay. The activity of superoxide dismutase (SOD) in serum was detected by colorimetry. The content of malondialdehyde (MDA) in serum was detected by thibabituric acid method. RESULTS: Morris water maze test showed that the times of crossing platform, and the swimming time and distance in the fourth quadrant in HNYCF groups were much more than those in model group. The step-down test manifested that the escape latency in HNYCF high-dose group was significantly longer than that in model group. Compared with model group, the expression of NF-κB obviously decreased, the expression of PPARγ significantly increased and the content of IL-6 was lower in HNYCF groups. The activity of serum SOD in HNYCF groups was significantly higher than that in model group. CONCLUSION: HNYCF evidently ameliorates the learning and memory ability in APP transgenic mice, which may be related to the anti-inflammatory and anti-oxidation effects of HNYCF.     

Effects of rolipram on learning and memory and the activity of PDE4 in hippocampus following the focal brain injury induced by ischemia- reperfusion in rats

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.     

Protective effect of paeoniflorin on nerve cells in APP/PS1 mice and its mechanism

AIM: To investigate the therapeutic and preventive effects of paeoniflorin (PF) on APP/PS1 mice, and to explore the possible mechanism. METHODS: Fifteen male 5-month-old APP/PS1 non-dominant mice were chosen as normal control group, 15 male 5-month-old APP/PS1 double transgenic mice were used as model group, and 15 male 5-month-old APP/PS1 double transgenic mice treated with 5 mg/kg PF by intraperitoneal injection were allocated in administation group. The learning and memory ability of the mice in each group was detected by Morris water maze. The apoptosis was assessed by TUNEL fluorescence staining. The protein expression of PI3K, Akt, p-PI3K, p-Akt, caspase-3, caspase-9, Bcl-2 and Bax in cerebral cortex and hippocampus was detected by Western Blot. The protein expression levels and distribution of caspase-3 and caspase-9 were detected by immunohistochemistry. RESULTS: (1) Compared with normal control group, the learning and memory ability declined in APP/PS1 model group. Compared with APP/PS1 model group, PF obviously improve the ability of learning and memory in mice. (2) Compared with normal control group, the apoptosis of nerve cells in APP/PS1 model group significantly increased and distributed in wider areas, while that in PF group was reduced (P<0.05). (3) Compared with APP/PS1 model group, PF could significantly lower pro-apoptotic factors, caspase-3, caspase-9 and Bax (P<0.05), and increase the expression of anti-apoptotic factors, p-PI3K, p-Akt and Bcl-2 (P<0.05). CONCLUSION: PF can up-regulate the expression of Bcl-2 and down-regulate the expression levels of caspase-9, caspase-3 and Bax via the activation of PI3K/Akt pathway, thereby inhibiting the nerve cell apoptosis and protecting the nerve cells, so as to treat neurodegenerative diseases.     

Effect of Buyanghuanwu decoction on the expression of ERK2 and CaMKⅡβ in hippocampus tissue and on ability of learning and memory in vascular dementia rats

AIM: To investigate the effect of Buyanghuanwu decoction, a Chinese medicine, on the ability of learning and memory in the rats with vascular dementia (VD) and on the protein expression of extracellular signal-regulated kinase 2(ERK2) and calcium/calmodulin-dependent protein kinase Ⅱβ(CaMKⅡβ) in hippocampus CA1 area.METHODS: The rats were divided into 4 groups: sham group, VD group, VD+Buyanghuanwu decoction group and VD+nimodipine group. The VD rat model was prepared by Pulsinelli's four-vessel occlusion. At 7th day, 14th day or 28th day after operation, the behaviors of the rats were tested by Morris water maze. The morphological changes of the neurons in hippocampus CA1 area were observed by HE staining 30 d after operation. Western blotting was used to observe the protein expression of ERK2 and CaMKⅡβ in the brain tissues of hippocampal CA1 area of the VD rats. RESULTS: Compared with sham group, the pathological changes such as irregular arrangement, coagulation necrosis and obvious deletion in the neurons of hippocampus CA1 area in VD group appeared significantly. The obstacle of learning and memory ability was observed and the protein expression of ERK2 and CaMKⅡβ in hippocampal CA1 area was significantly decreased (P<0.05). Compared with VD group, the neurons in hippocampal CA1 area of VD+Buyanghuanwu decoction group and VD+nimodipine group were in eumorphism, lined up in order, and the structure was close to that in sham group. The ability of learning and memory also significantly improved (P<0.05). The protein expression of ERK2 and CaMKⅡβ in hippocampal CA1 area significantly increased (P<0.05). CONCLUSION: Buyanghuanwu decoction promotes the protein expression of ERK2 and CaMKⅡβ in hippocampus CA1 area to protect the neurons from injury, builds up the synapses and promotes the ability of learning and memory in VD rats.     

Influences of Vit-E on the mtDNA damage and Ca2+ homostasis of hippocampus and antioxidative ability in brain of aging mice induced by D-galactose

AIM: To study the influences of vitamin E (Vit-E) on the mtDNA damage and Ca²⁺ homeostasis in hippocampus and antioxidative ability in aging brain induced by D-galactose.METHODS: D-galactose (1 000 mg·k^-1·d^-1 ) was injected into mice hypodermically for 8 weeks to induce aging animal model, and Vit-E (100 mg·kg^-1; 250 mg·kg^-1) was administered for 6 weeks by ig at the 3rd week of making model. After Vit-E treatment for 8 weeks, water maze test was used to determine the ability of mice’s learning and memory. The activities of glutathione peroxidase (GSH-Px) and succinate dehydrogenase (SDH), the content of nitric oxide (NO) and activity of nitric oxide synthase (NOS) in the brain tissue were detected separately. Fura-2/AM, double-wave-length fluorospectrophotometer and PCR method were used to measure the concentration of calcium ion and mtDNA mutation in the hippocampus cells.RESULTS: Administration of Vit-E improved significantly the ability of learning and memory in model mice, inhibited the activity of NOS and decreased the amount of NO, and increased the activities of GSH-Px and SDH respectively in brain tissues, decreased the concentration of calcium ion (P<0.01, P<0.05), and prevented the damage of mtDNA in hippocampus.CONCLUSION: Vit-E can enhance the antioxidative ability, regulate the homeostasis of Ca²⁺ and inhibit the damage of mtDNA caused by oxidative stress in aging brain, and improve the ability of learning and memory in aging mice.     

Expression of synaptophysin in hippocampal CA1 region and prefrontal cortex of PTSD rats

AIM:To investigate the expression of synaptophysin in the CA1 region of hippocampus and prefrontal cortex (PFC) of rats with posttraumatic stress disorder (PTSD), and to explore the mechanism of spatial memory changes in PTSD rats.METHODS:Healthy adult SD rats (n=36) were randomly divided into 2 groups:control group and model group, with 18 rats in each group. The rats in model group was continuously given single prolonged stress (SPS) to construct the PTSD model. Morris water maze (MWM) was used to test the learning and memory ability of the rats in the 2 groups. The protein expression of synaptophysin in the hippocampal CA1 area and PFC was examined by immunohistochemistry, Western blot and immunofluorescence experiments. RESULTS:The latency of the rats in searching for the underwater platform in model group was significantly longer than that in control group from the 2nd day (P<0.01) in the MWM experiment, the target quadrant swimming time was significantly shortened (P<0.01), and the times of crossing the platform were also significantly reduced (P<0.01). The results of immunohistochemistry, Western blot and immunofluorescence experiments showed that the expression of synaptophysin was obviously reduced in the CA1 region of hippocampus and PFC in model group as compared with control group (P<0.05 or P<0.01).CONCLUSION:The reduction of spatial memory ability in PTSD rats may be associated with the decreased expression of synaptophysin in the CA1 region of hippocampus and PFC.     

Effects of clonidine on learning and memory and protein levels of ERK signal pathway-related proteins in rats with chronic cerebral ischemia

AIM:To investigate the regulatory effects and underlying molecule-mechanism of clonidine on learning and memory in rats with chronic cerebral ischemia. METHODS:Sprague-Dawley rats (n=45) were randomly divided into sham-operation group, cerebral ischemia model group and clonidine group, 15 rats in each group. The chronic cerebral ischemia rat model was established by right middle cerebral artery occlusion for 2 h and reperfusion for 30 d. Clonidine was administrated by i.g. for 7 days in clonidine group. The ability of spatial reference memory of the rats with cerebral ischemia was tested by Morris water maze. The protein levels of extracellular signal-regulated kinase 1/2 (ERK1/2), phosphorylated ERK1/2 (p-ERK1/2), cAMP-response element binding protein (CREB) and phosphorylated CREB (p-CREB) were determined by immunohistochemistry and Western blot. RESULTS:The results of Morris water maze test showed that compared with the sham-operation group, the ability of spatial reference memory was obviously impaired in the cerebral ischemia model group. Compared with the cerebral ischemia model group, the ability of spatial reference memory in the clonidine group were improved. Compared with the sham-operation group, the protein levels of p-ERK1/2 and p-CREB in hippocampus were increased in model group (P<0.01). Compared with the cerebral ischemia model group, the protein levels of p-ERK1/2 and p-CREB in hippocampus were decreased in the clonidine group (P<0.01). CONCLUSION:Clonidine improves the learning and memory abilities of the rats with cerebral ischemia, and ERK1/2 and CREB are involved in this process.     

The effect of buyanghuanwu decoction on expression of AMPA receptor GluR1 subunit in mRNA and protein levels in rat hippocampus with vascular dementia

AIM: To observe the effect of buyanghuanwu decoction, a Chinese medicine, on the expression of AMPA receptor GluR1 subunit in mRNA and protein levels in rat hippocampus with vascular dementia (VD). METHODS: One hundred and forty-four rats were randomly divided into 4 groups: sham-operation group, VD model group, nimodipine group and buyanghuanwu decoction treatment group. The rat model of VD was built up by the method of 4 vessel occlusion. The VD rats were intragastrically treated with buyanghuanwu decoction suspension (pharmacognostic 50 g·kg-1·d-1) and nimodipine suspension (20 mg·kg-1·d-1) for 30 d. The learning and memory abilities were evaluated by Morris water maze testing. The change of GluR1 protein in hippocampal neurons in each group of rats was measured with immunohistochemistry and Western blotting techniques. The expression of GluR1 mRNA in hippocampus was determined by real-time fluorescence quantitative PCR. RESULTS: Compared to sham-operation group, the average escaping latency period (s) of Water maze tests in VD rats prolonged significantly and cross-platform time (numbers/min) shortened distinctly (P<0.05). The VD rats treated with buyanghuanwu decoction significantly improved the above-mentioned learning and memory performances (P<0.05); no significant difference of above-mentioned learning and memory performances among the rats in sham-operation group, nimodipine group and buyanghuanwu decoction treatment group was observed (P>0.05). Compared to the rats in sham-operation group, the mRNA and protein levels of GluR1 were apparently decreased in VD rats (P<0.05). The mRNA and protein levels of GluR1 in the neurons of hippocampus in buyanghuanwu decoction treated VD rats were higher than those in the model animals (P<0.05), and no difference was discovered in the rats among sham operation group, buyanghuanwu decoction treatment group and nimodipine group (P>0.05). CONCLUSION: Buyanghuanwu decoction improves the learning and memory abilities in VD rats. The therapeutic mechanism is associated with lessening the neuron injury on CA1 field in hippocampus and restoring the mRNA and protein expression of GluR1.     

Molecular mechanism of BMSC intracerebral transplantation in improving learning and memory abilities of AD mice

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.     

Effect of TAK-242 on learning and memory dysfunction in mice with lipopolysaccharide-induced sepsis-associated encephalopathy

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).     

Effect of curcumin on learning-memory ability and expression of HMGB1 and JNK in rat model of Alzheimer disease

AIM: To evaluate the effect of curcumin on impaired learning-memory ability and the expression of high mobility group box protein 1 (HMGB1) and c-Jun N-terminal kinase (JNK) in a rat model of Alzheimer disease (AD). METHODS: Male Sprague-Dawley rats, weighing 250~270 g, were randomly divided into 4 groups (n=9): blank control group (group A), model group (group B), curcumin treatment group (group C, curcumin injected intraperitoneally at 100 mg·kg-1·d-1 for 6 consecutive days) and solvent control group (group D). The rats of AD model were induced by injection of ibotenic acid into the nucleus basalis of Meynert (NBM) bilaterally. All rats were trained in Morris maze to assess the ability of learning and memory. The expression of HMGB1 and JNK in the hippocampus was detected by the methods of immunohistochemistry and Western blotting. RESULTS: Compared with group A, the average escape latency (AEL) in groups B and D were obviously longer (P<0.05), while AEL in group C in the 5th and 6th days were significantly shorter (P<0.05). The releases of HMGB1 in the CA1 and CA3 areas in groups B and D from the nucleus were abundant. Compared with groups B and D, HMGB1 in hippocampal CA1 and CA3 areas in group C secreted out of the nucleus decreased obviously (P<0.05). No significant difference of the release of HMGB1 between group A and group C was observed (P>0.05). No significant difference in the expression of HMGB1 in the hippocampus among the 4 groups was found (P>0.05). However, compared with groups B and D, the expression of JNK in group C was decreased obviously (P<0.05). CONCLUSION: Curcumin significantly improves the learning and memory ability of AD rats. The probable mechanisms may be related to inhibiting the release of HMGB1 from the nucleus of hippocampal neurons and decreasing the expression of JNK in the hippocampus.     

Effect of 5-HT1A receptor in hippocampal CA1 region on spatial memory of PTSD rats

AIM: To investigate the change of long-term potentiation (LTP), and the expression of 5-hydroxytryptamine 1A receptor (5-HT_1A receptor) and postsynaptic density protein 95 (PSD-95) in the hippocampus of the rats with posttraumatic stress disorder (PTSD), and to explore the mechanism of 5-HT_1A receptor in the regulation of spatial memory in the PTSD rats.METHODS: Healthy adult SD rats (n=36) were randomly divided into control group and model group, with 18 rats in each group. The rats in model group were treated with single prolonged stress to construct the model of PTSD. Morris water maze (MWM) was used to test the learning and memory ability. The LTP induced by high-frequency stimulation (HFS) was detected by electrophysiological method. The protein expression of 5-HT_1A receptor and PSD-95 in the hippocampus was determined by Western blot and immunofluorescence. RESULTS: The MWM analysis showed that the latency of the rats searching for the underwater platform in model group was significantly longer than that in control group (P<0.01). The results of electrophysiological analysis showed that the amplitude of the evoked potential in both groups were significantly increased after HFS in the hippocampus, but that in model group was significantly lower than that in control group (P<0.01). The results of Western blot and immunofluorescence analysis showed that compared with control group, the protein expression of 5-HT_1A receptor was obviously increased (P<0.05), while the expression of PSD-95 was obviously decreased in model group (P<0.05).CONCLUSION: The spatial memory impairment in the PTSD rats may be associated with the increase in the expression of 5-HT_1A receptor and the decrease in the expression of PSD-95 in the CA1 region of hippocampus.     

Transplantation of human amnion epithelial cells improves learning and memory function in Alzheimer's disease-like pathology rat model

AIM: To observe the treatment effect and its immune regulation of human amnion epithelial cells (hAECs) on Alzheimer's disease (AD)-like pathology rat model. METHODS: The hAECs were isolated from amnion with trypsin digestion, and the phenotype of hAECs was analyzed by flow cytometry. SD rats (n=48) were randomly divided into sham control group, model group, medium group and hAECs group. AD-like pathology rat model was induced by bilateral intraventricular injection of lipopolysaccharide (LPS). hAECs (5×10⁵) were injected into the hippocampus of the AD-like pathology rats. At 2 weeks after transplantation, the animals were tested by Morris water maze to observe the function of learning and memory. The pathological change of the brain was observed by HE staining. The expression of amyloid β-protein 42(Aβ42) and Tau protein and the level of acetylcholine (ACh) in the injury brain were determined by immunohistochemistry. The survival and differentiation of hAECs in the hippocampus were measured by immunofluorescent technique. The percentages of lymphocyte subsets in the peripheral blood mononuclear cells were analyzed by flow cytometry. The contents of serum cytokines were detected by cytometric bead array. RESULTS: Compared with model group and medium group, hAECs group showed shortened escape latency (P<0.01), increased frequency of going through the platform (P<0.05), reduced loss of hippocampal neurons, decreased expression of Tau protein and Aβ42 in the hippocampus (P<0.05), increased ACh level in the hippocampus (P<0.05), decreased percentages of Th1 and Th17 subsets, increased percentages of Th2 and Treg cells (P<0.05), decreased concentrations of IFN-γ and IL-2 in the serum, and increased concentration of IL-4(P<0.05). CONCLUSION: hAECs improve the cognitive learning and memory function and alleviate pathologic damage of hippocampus through immune regulation in AD-like pathology rats.     

Effects of maternal high-fat diet on motor ability,learning and memory of male offspring mice in late adolescence

AIM To study the effects of maternal high-fat diet （HFD） on motor ability， learning and memory of male offspring mice in late adolescence and the underlying mechanism. METHODS The female rats were fed with HFD for 16 weeks until the end of lactation to establish the obesity model， and the offspring male rats were taken as the main research object. The motor coordination of offspring mice was studied by footprinting analysis and rotarod experiment， the change of motor ability of male offspring mice was studied by open field experiment， the change of learning memory behavior of offspring mice was studied by Morris water maze and new object recognition experiment， and the neurogenesis of dentate gyrus （DG） in hippocampus of offspring mice was observed by immunofluorescence staining. RESULTS The footprint angle of the offspring mice in maternal HFD group decreased significantly， and the stay time in rotarod of the offspring mice in maternal HFD group was significantly shorter than that of the offspring mice in maternal normal diet group（P<0.01）. In the open field experiment， the number of vertical times， the central time and the total distance of movement were significantly reduced， and the latency of water maze experiment and the preference index of new object recognition were significantly reduced. The results of immunofluorescence staining showed that the degree and complexity of neuron differentiation in DG area of hippocampus of offspring mice in maternal HFD group decreased significantly（P<0.01）. CONCLUSION Maternal HFD damages the movement and learning abilities of the male offspring in late adolescence by affecting the hippocampus neurogenesis.     

Effects of EGb761 on synaptophysin expression in hippocampus of vascular dementia rats

AIM: To investigate the effects of Ginkgo biloba extract 761 (Egb761) on synaptophysin (SYN) expression in hippocampus of vascular dementia (VD) rats.METHODS: VD rat models, established by repeatedly cerebral ischemia/reperfusion, were randomly divided into two groups: model group and EGb761 treated group (both n=30), and another 30 condition-matched rats were selected as the sham-operated controls. Spatial learning and memory abilities of rats were assessed by Morris water maze (MWM) task, and SYN expression in hippocampal formation of rats in different groups was detected by immunohistochemical technique and image analysis.RESULTS: The MWM escape latency (EL) in model group was highly longer than that in the sham-operated group (P<0.01), while the EL of EGb761-treated group was significantly shorter than that in model group, but still longer than that in the sham-operated group at 1 m, 2 m and 4 m after VD modeling operation (P<0.05 or P<0.01). Immunohistochemical analysis showed that the SYN immunoreactive expression in hippocampal formation in model group greatly decreased and mean optical density of SYN expression highly increased compared with both sham-operated group and EGb761-treated group at three time points (P<0.01).CONCLUSION: EGb761 can increase the expression of SYN in hippocampus, which may be one of important mechanisms of EGb761 in improving learning and memory dysfunction of VD rats.