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1.
JIANG Li-ying TANG Su-su WANG Xiao-yun LIU Li-ping LONG Yan HU Mei LIAO Ming-xing DING Qi-long HU Wei LI Jia-chang HONG Hao . 《中国药理学与毒理学杂志》2012,(3):437
OBJECTIVE Pioglitazone,known as a peroxisome proliferator-activated receptor γ(PPARγ) agonist,is used to treat type 2 diabetes(T2DM).T2DM has been associated with reduced performance on numerous domains of cognitive function.Here,we investigated the effects of pioglitazone on memory impairment in a mouse model with defects in insulin sensitivity and secretion,namely high-fat diet(HFD) streptozotocin(STZ)-induced diabetic mice.METHODS ICR mice were fed an HFD for 4 weeks and then injected with a single low dose of STZ followed by continued HFD feeding for an additional 4 weeks.The diabetic mice were orally administered with pioglitazone(9,18 mg·kg-1) for 4-5 weeks.Y-maze test and Morris water maze test(MWM) were employed for testing learning and memory.Serum glucose,serum insulin,serum triglyceride,brain amyloid peptide-β(Aβ),brain β-site amyloid precursor protein cleaving enzyme(BACE1),brain nuclear factor κB(NF-κB),brain receptor for advanced glycation end products(RAGE) were also tested.RESULTS The STZ/HFD diabetic mice,characterized by hyperglycemia,hyperlipemia and hypoinsulinemia,performed poorly on Y-maze and MWM hence reflecting impairment of learning and memory behavior with increases of Aβ40/Aβ42,BACE1,NF-κB,and RAGE in brain.Treatment of PPARγ agonist,pioglitazone,significantly reversed diabetes-induced impairment of learning and memory behavior,which is involved in decreases of Aβ40/Aβ42 via inhibition of NF-κB,BACE1 and RAGE in brain as well as attenuation of hyperglycemia,hyperlipemia and hypoinsulinemia.CONCLUSION It is concluded that PPARγ agonist pioglitazone may be considered as potential pharmacological agents for the management of cognitive dysfunction in T2DM. 相似文献
2.
Objective To observe the effect of Lycopene on the improvement of memory abilities by cumulating lactic acid for long time in atlas dentata vertebrae senile mice. Methods Totally 30% lactic acid 30μL one time every week was injected into the place between the first and the second cervical vertebrae for 3 weeks. Forty mice were randomized into five groups:young control group, model group, VitE group(50 mg/kg), control group,and two therapeutic groups of lycopene which was intragastric at the doses of 5, 2.5 mg/kg once everyday. The changes of memory in mice were observed with water-maze test and step-down avoidance test. The activities of acetylcholine esterase(AchE), and the content of acetylcholine, (Ach) in encephalon were tested. HE staining in mice brain, including the cortex and hippocampus was demonstrated. Results Compared with model group. Lycopene high dose could significantly shortened the latency period and wrong times in water-maze test (P <0.01 ), In stepdown avoidance test, the reaction period was shortened significantly ( P < 0.01 ) and the latency period was shortened significantly. The activities of ChE decreased (P <0.01 ) and the content of ACh increased in the Lycopene high doses group(P<0.01 ). The therapeutic groups of lycopene had less pathological change of cellular necrosis,neuron loss in hippocampal CAI than the model group. Conclusion Lycopene has a certain protective and improving effect on the decline of memory ability and cervical lesion induced by lactic acid in atlanto-axial joint cumulating. 相似文献
3.
Objective To observe the effect of Lycopene on the improvement of memory abilities by cumulating lactic acid for long time in atlas dentata vertebrae senile mice. Methods Totally 30% lactic acid 30μL one time every week was injected into the place between the first and the second cervical vertebrae for 3 weeks. Forty mice were randomized into five groups:young control group, model group, VitE group(50 mg/kg), control group,and two therapeutic groups of lycopene which was intragastric at the doses of 5, 2.5 mg/kg once everyday. The changes of memory in mice were observed with water-maze test and step-down avoidance test. The activities of acetylcholine esterase(AchE), and the content of acetylcholine, (Ach) in encephalon were tested. HE staining in mice brain, including the cortex and hippocampus was demonstrated. Results Compared with model group. Lycopene high dose could significantly shortened the latency period and wrong times in water-maze test (P <0.01 ), In stepdown avoidance test, the reaction period was shortened significantly ( P < 0.01 ) and the latency period was shortened significantly. The activities of ChE decreased (P <0.01 ) and the content of ACh increased in the Lycopene high doses group(P<0.01 ). The therapeutic groups of lycopene had less pathological change of cellular necrosis,neuron loss in hippocampal CAI than the model group. Conclusion Lycopene has a certain protective and improving effect on the decline of memory ability and cervical lesion induced by lactic acid in atlanto-axial joint cumulating. 相似文献
4.
Objective To study the preventive effect of rosiglitazone glial activation,oxidative/nitrative stress and spatial memory deficits induced by intracerebroventricular(ICV)injection of streptozotocin(STZ)in rats.Methods 24 male Wistar rats were randomly divided into sham operated group,model group and rosiglitazone group.The model of Alzheimer's was induced by injection with ICV 10% STZ bilaterally,on day 1 and 3(3 mg·kg-1).The rats were treated with rosiglitazone(2 mg·kg-1,p.o.)for a consecutive 21 days,once a day,beginning 7 days prior to STZ injection.The learning and memory behavior was assessed using Morris water maze task and Y-maze 21 d after ICV STZ injection.Malondialdehyde(MDA),superoxide dismutase(SOD),glutathione(GSH)levels and nitrotyrosine immunoreactivity in brain were estimated as parameters of oxidative/nitrative stress.Brain acetyl cholinesterase(AchE)activity was measured by EllMann's method and activated microglia and astrocytes were detected by immunohistochemistry.Results ICV STZ injection resulted in a severe deficit in spatial learning and memory associated with increased MDA level(+69.5%)and nitrotyrosine immunoreactivity(+23.7%),decreased SOD activity(-29.2%)and GSH(-25.1%)in brain.It also showed the activated microglia and astrocytes in the cortex and hippocampal CA1 region and a significant decrease in acetylcholinesterase activity(-40.2%).Compared with model group,chronic administration of rosiglitazone significantly shorten the escape latency time from the third day in place navigation test,increase the number of passing through primary flat place in spatial probe test in Morris water maze test,and decrease the error times in Y-maze test(P<0.05 or P<0.01).In addition,it also prevented the glial changes,decreased the elevated MDA and nitrite levels and restored the depleted GSH and acetylcholinesterase activity in cortex(P<0.05),but had no effect on SOD activity in cortex.Conclusions Rosiglitazone has a neuroprotective role against streptozotocin-induced cognitive impairment and associated oxidative/nitrative stress. 相似文献
5.
This study examined the protective effects of icariin (ICA) on the learning and memory deficits in Aluminium (Al) -treated rats and potential mechanisms. The screened, qualified rats were treated with 1. 6 g/L AlCl3 in drinking water for 8 months, and the ability of spatial learning and memory was tested by Morris water maze. Aluminium (Al) administration significantly increased the mean escape latency searching distance in place navigation test, and decreased the searching time in the quadrant once the platform was in space probe test and adjusted searching distance in space probe test, indicative of brain spatial learning and memory deficits. ICA treatment (60, 120 mg/kg, i. g 3 month) significantly protected against Al-induced spatial learning and memory deficits, as evidenced by decreased escape latency and searching distance, and by increased the searching time in the quadrant once the platform was adjusted via searching distance compared with the Al alone group. To examine the mechanisms of the protection, the activities of superoxide dismuase (SOD) and the contents of maloidaldehyde (MDA) in hippocampus were assayed by commercial kits, and the level of Aβ1-40 in hippocampus was examined by immunohistochemistry (IHC), respectively. ICA treatment significantly increased the activities of SOD, decreased the content of MDA and the level of Aβ1-40 in hippocampus in a dose - dependent manner. In summary, this study demonstrates that ICA is effective in improving the ability of spatial learning and memory of Al-intoxicated rats. 相似文献
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7.
Ping-ping LI ;Wei-ping WANG ;Zhi-hui LIU ;Shao-feng XU ;Wen-wen LU ;Ling WANG ;Xiao-liang WANG 《Acta pharmacologica Sinica》2014,35(7):869-878
Aim: Potassium 2-(1-hydroxypentyl)-benzoate (d/-PHPB) is a new drug candidate for ischemic stroke. The aim of this study was to investigate the effects of dI-PHPB on memory deficits and long-term potentiation (LTP) impairment in animal models of Alzheimer's disease. Methods: The expression of NMDA receptor subunits GluN1 and GluN2B in the hippocampus and cortex of APP/PS1 transgenic mice were detected using Western blot analysis. Memory deficits of the mice were evaluated with the passive avoidance test. LTP impairment was studied in the dentate region of Aβ1-42-injected rats and APP/PS1 transgenic mice. Results: APP/PS1 transgenic mice showed significantly lower levels of GluN1 and p-GluN2B in hippocampus, and chronic administration of dI-PHPB (100 mg·kg-1·d1, po) reversed the downregulation of p-GluN2B, but did not change GluN1 level in the hippocampus. Furthermore, chronic administration of d/-PHPB reversed the memory deficits in APP/PS1 transgenic mice. In the dentate region of normal rats, injection of dI-PHPB (100 μmol/L, icv) did not change the basal synaptic transmission, but significantly enhanced the high-frequency stimulation (HFS)-induced LTP, which was completely prevented by pre-injection of APV (150 μmol/L, icv). Chronic administration of dI-PHPB (100 mg·kg-1·d-1, po) reversed LTP impairment in Aβ1-42 -injected normal rats and APP/PS1 transgenic mice. Conclusion: Chronic administration of d/-PHPB improves learning and memory and promotes LTP in the animal models of Alzheimer's disease, possibly via increasing p-GluN2B expression in the hippocampus. 相似文献
8.
Aim: Hippocampal neuronal network and synaptic impairment underlie learning and memory deficit in Alzheimer's disease (AD) patients and animal models. In this paper, we analyzed the dynamics and complexity of hippocampal neuronal network synchronization induced by acute exposure to carbachol, a nicotinic and muscarinic receptor co-agonist, using the nonlinear dynamical model based on the Lempel-Ziv estimator. We compared the dynamics of hippocampal oscillations between wild-type (WT) and triple-transgenic (3xTg) mice, as an AD animal model. We also compared these dynamic alterations between different age groups (5 and 10 months). We hypothesize that there is an impairment of complexity of CCh- induced hippocampal oscillations in 3xTg AD mice compared to WT mice, and that this impairment is age-dependent. Methods: To test this hypothesis, we used electrophysiological recordings (field potential) in hippocampal slices. Results: Acute exposure to 100 μmol/L CCh induced field potential oscillations in hippocampal CA1 region, which exhibited three distinct patterns: (1) continuous neural firing, (2) repeated burst neural firing and (3) the mixed (continuous and burst) pattern in both WT and 3xTg AD mice. Based on Lempel-Ziv estimator, pattern (2) was significantly lower than patterns (1) and (3) in 3xTg AD mice compared to WT mice (P〈0.001), and also in 10-month old WT mice compared to those in 5-month old WT mice (P〈0.01). Conclusion: These results suggest that the burst pattern (theta oscillation) of hippocampal network is selectively impaired in 3xTg AD mouse model, which may reflect a learning and memory deficit in the AD patients. 相似文献
9.
Aging is an inevitable process featured by intelligence decline,behavioral disorders and cognitive disability.Increasing evidence indicates that oxidative stress plays a key role in the senescent development.Our previous study demonstrated that Saponins from Panax japonicus has a significant anti-oxidative effect in vitro.So the aim of the present study was to investigate the brain protective role of Saponins from Panax japonicus and its underlying mechanism.Mice were subcutaneously injected with D-galactose(D-gal,150 mg·kg-1·d-1) for 8 weeks and administered Saponins from Panax japonicus simultaneously.After 8 weeks of treatment,the animal behavior was observed in the open field test and water maze test,and the morphology of hippocampus was detected.The activities and mRNA expressions of antioxidant enzymes as well as the level of malondialdehyde(MDA) were evaluated.The extent of apoptosis was examined by TUNEL assay.The results indicate that Saponins from Panax japonicus markedly ameliorates the D-gal induced learning and memory impairment in both open field test and Morris water maze.Biochemical examination and RT-PCR method revealed that Saponins from Panax japonicus significantly increases the decreased activities and mRNA expressions of superoxide dismutase(SOD),catalase(CAT) and glutathione peroxidase(GSH-Px) and decreases the raised malondialdehyde(MDA) content in the serum and brain of aging mice induced by D-gal.Furthermore,Saponins from Panax japonicus significantly attenuates the D-gal-induced neuronal degeneration and apoptosis in the hippocampus.These results indicate that Saponins from Panax japonicus has a potential protect role on brain aging mice induced by D-gal and its mechanism,at least in part,via modification of the redox system in the organism. 相似文献
10.
Aim: To study the Central pharmacological effect of the water - and chloroform - extract compounds from Cynanchum Chinese R. Br. Methods: The minimal neurotoxicity of the extract - compounds were measured by rotorod test. The Independent activity test and the hypnotic synergism test by under threshold hypnotic dosage of pentobarbital were employed to evaluate the central pharmacological action of the extract - compounds. All the extract - compounds were evaluated for anticonvulsant activity by maximal electroshock (MES) and subcutaneous metrazol (MET) induced seizure. Result: The extract - compounds significantly inhibited the spontaneous motor activity dose - dependently in mice after intraperitoneal administration. The two extract - compounds promoted the hypnotic effect by under threshold hypnotic doses of pentobarbital, and the ED50 values were 2.36 g/kg and 0. 75 g/kg, respectively. Meanwhile, the water - extract compounds exhibited significant protection after intraperitoneal (ip) administration in MET - induced seizures and the ED50 value was 2.34 g/kg; however, the chloroform - extract compounds did not produced protective effect in this seizure model. On the other hand, the chloroform - extract compounds exhibited significant protection in MES and the ED50 value was 1.34 g/kg; the water- extract compounds had no protective effect. Both extract -compounds showed no neurotoxicity as compared with phenytoin. Conclusion : The extract compounds from Cynanehum Chinese R. Br show inhibition effect on CNS, and the water - and chloroform - extract compounds show different anticonvulsant activities in different seizure models in mice. 相似文献
11.
XUJiang-Ping WUHang-Yu LILin 《中国药理通讯》2004,21(2):32-32
AIM: To explore the effects of Compound Yi-Zhi (YZC) on learning and memory capacity and free radical metabolism in D-galactose induced mice dementia model. METHODS: The mice dementia model was induced by a daily D-galactose 0.15g/kg sc for 45 days and after 5 days‘D-galactose injection, the mice were treated with three doses of YZC 相似文献
12.
张聪 《中国药理学与毒理学杂志》2012,(3):437
OBJECTIVE Here we examined whether long-form PDE4Ds reversed memory impairment produced by Aβ1-42(Aβ42).METHODS Morris water-maze and novelty object recognition tests were used for memory measurements.Western blotting analysis was used for determination of the expression of CREB,pCREB,BDNF,IL-1β,TNF-α and NF-κB in order to explore the neurochemical mechanisms.RESULTS Aged Aβ42(0.5 μg/side) infused in bilateral dentate gyri produced memory deficits in the Morris water-maze(P<0.0001) and object recognition tests(P=0.0004) in mice.Microinfusions of lentiviral vectors containing miRNAs that target long-form PDE4D variants reversed Aβ42-induced memory deficits and concomitantly increased pCREB(P=0.0001) and BDNF(P<0.0001),and reduced inflammatory cytokines,including IL-1β(P=0.0026),TNF-α(P<0.0001),and NF-κB(P<0.0001) in the hippocampus of Aβ42-treated mice.CCONCLUSION These results suggest that long-form PDE4D variants maybe potential targets for treatment of memory loss associated with Alzheimer′s disease. 相似文献
13.
楚世峰 《中国药理学与毒理学杂志》2012,(3):463
The aim of present study is to observe the effect of ginsenoside Rg1′s metabolites(primary metabolit ginsenoside Rh1 and end metabolite protopanaxatriol) on learning and memory function.we employed the step through test and electrophysiological study to investigate the effects of Rh1 and Ppt on learning and memory as well as hippocampal excitability.The behavioral study showed that both ginsenoside Rh1 and Ppt significantly ameliorated memory-impaired model induced by scopolamine in mice.Consistently,electrophysiological work revealed that Rh1 and Ppt as well as their precursor Rg1 all increased hippocampal excitability in the dentate gyrus of anesthetized rats.The metabolism of Rg1 in cerebrospinal fluid was detected by HPLC-MS,indicating that Rg1 could not convert into Rh1 or Ppt.These results demonstrated that both Rh1 and Ppt have similar effect on improving memory and hippocampal excitability,suggesting that the role of ginsenoside’s sugar moeties in biological activities is not as necessary as traditionally considered. 相似文献
14.
Aim: To investigate the effect of EUK1001, one of derivatives of xanomeline, on the learning and memory as well as hippocampal synaptic plasticity in aging mice. Methods: Mice were i.p.injected respectively with saline, xanomeline (0. 5mg/Kg ) and EUK1001 (0.5mg/Kg and 1 mg/kg) for 15 days before they were tested by a novel object recognition task. Effects of EUK1001 (0. 1 and 1μm) on the synaptic plasticity of CA3- CA1 in hippocampus were also investigated using in vitro electrophysiological technique. Results: The derivatives of xanomeline, such as EUK1001, improve the performance of aging mice in the novel object recognition test, like xamomeline. In addition, bath application of low concentration (0. 1 and lμm) of EUK1001 induced long term potentiation (LTP) in the hippocampus. This EUK1001-induced effect can be blocked completely by pirenzepine dihydrochloride (0. 25μm), an antagonist of Ach receptor. Conclusion: EUK1001 ameliorates the normal aging related memory deficits. This effect on hippocampaldependent memory is mediated by enhancing synaptic plasticity of hippocampus. 相似文献
15.
Centrophenoxine improves chronic cerebral ischemia induced cognitive deficit and neuronal degeneration in rats 总被引:13,自引:0,他引:13
AIM:To study the effects of centrophenoxine (CPH, meclofenoxate) on chronic cerebral hypoperfusion induced deficits in rats. METHODS: Chronic hypoperfusion in rats was performed by permanent bilateral ligation of the common carotid arteries. Morris water maze was used to measure spatial memory performance. Spectrophoto-metrical techniques were used to assay SOD, GPx activities, MDA content, TXB2, and 6-keto-PGF1α levels. Morphological change was examined by HE staining. The expression of Bax and p53 protein were assayed by immunohistochemistry analysis. RESULTS: Chronic hypoperfusion in rats resulted in spatial memory impairments shownby longer escape latency and shorter time spent in the target quadrant. These behavioral dysfunction were accom-panied by increase in SOD and GPx activities, the content of MDA, the levels of pro-inflammatory mediators(TXB2, 6-keto-PGF1α, overexpression of Bax and P53 protein, and delayed degeneration of neurons in cortex andhippocampus. Oral administration of CPH (100 mg/kg, once per day for 37 d) markedly improved the memory impairment, reduced the increase in antioxidant enzyme activities, MDA content and the levels of pro-inflammatorymediators to their normal levels, and attenuated neuronal damage. CONCLUSION: The abilities of CPH to attenuate memory deficits and neuronal damage after ischemia may be beneficial in cerebrovascular type dementia. 相似文献
16.
The medicinal benefits of Allium vegetables, especially garlic, have been noted throughout recorded history. The known health benefits of Allium vegetables and their constituents include cardiovascular protective effects, stimulation of immune function, reduction of blood glucose level, radioprotection, improvement of memory loss, protection against microbial, viral and fungal infections, as well as anticancer effects. Population-based case control studies have suggested an inverse correlation between dietary intake of Allium vegetables and the risk of different types of cancers. The anticarcinogenic effect of Allium vegetables including garlic is attributed to organosulfur compounds (OSC), which are highly effective in affording protection against cancer in animal models induced by a variety of chemical carcinogens. More recent studies have shown that certain naturally occurring OSC analogues can suppress proliferation of cancer cells in culture and in vivo. The OSC-induced changes in the proliferation of cancer cells are frequently associated with perturbations in cell cycle progression and induction of G2/M phase arrest. The OSC have also been demonstrated to induce apoptosis via the intrinsic pathway by altering the ratio of the Bcl-2 .family of proteins both in cell culture and in in vivo models. Anti-angiogenic activity for garlic-derived OSC has also been documented. This article summarizes current knowledge on molecular targets of cancer chemoprevention by OSC. 相似文献
17.
AIM: To explore the inhibitory effect of antisense oligonucleotide (ODN) to mitogen activated protein kinase(MAPK) on cardiomyocyte hypertrophy induced by angiotensin Ⅱ (Ang Ⅱ). METHODS: A 17-mer phosphorothioate-protected antisense ODN directed against the initiation of translation sites of the p42 and p44 MAPK isoforms byliposomal transfection was applied to inhibit the translation of p44/p42 MAPK mRNA. The sense and random ODNs to p44/p42MAPK were used as sequence controls. Neonatal cardiac myocytes were exposed to Ang Ⅱ (10nmol/L) for 5 min and then harvested in lysis buffer for the measurement of the activity and the phosphorylated protein content of p44/p42MAPK that were tested by P-81 phosphocellulose filter paper method and Western blotting, respectively. The rate of protein synthesis by [^3H]leucine incorporation and the diameter of cell were measured after exposure to Ang Ⅱ for 24 h and 72 h, respectively. RESULTS: In cardiac myocyte Ang Ⅱ increased p44/p42MAPK activity and phosphorylated protein content by 140 % and 699 %, and also increased [^3H]leucine incorporation and cell diameter by 40 % and 27 %. c-fos and c-myc mRNAs were induced significantly after exposure to Ang Ⅱ. Antisense ODN to p44/p42MAPK (0.2 μmol/L) reduced Ang Ⅱ-induced MAPK activity by 30 %,and phophorylated MAPK protein expression by 59 % in cardiac myocyte, and inhibited c-fos and c-myc mRNA expression induced by Ang Ⅱ by 44 % and 43 %, respectively. The diameter and the rate of protein synthesis of cardiac myocyte induced by Ang Ⅱ were decreased by 16 % and 22 % after pretreatment with antisense ODN to p44/p42MAPK. CONCLUSION: Antisense ODN to p44/p42 MAPK inhibited the increase of rate of protein synthesis,and the augmentation of cell diameter and expression of c-fos and c-myc mRNA induced by Ang Ⅱ in culturedcardiac myocytes, p44/p42 MAPK played a critical role in the hypertrophic response induced by Ang Ⅱ in cultured neonatal rat cardiac myocytes. 相似文献
18.
Inhibitory effect of picroside Ⅱ on hepatocyte apoptosis 总被引:5,自引:0,他引:5
19.
ItoY KosuY 《中国药理学与毒理学杂志》2002,16(6):405-406
Aged garlic extract and its components such as S-allyl-L-cysteine (SAC) and sllixin have been shown to possess various biological effects including neurotrophic activity.We characterized the neuronal death induced by amyloid β-protein (Aβ),4-hydroxynoenal (HNE),tunicamycin(TM),and trophic factor-deprivation (TFD),and ivestigated whether these garlic compounds could prevent this in cultured PC12 cells and rat hippocampal neurons.Treatment with SAC protected these cells against Aβ- and TM-induced neuronal death.SAC also attenuated the processing of procaspase-12 induced by Aβ25-35 or TM.In contrast,allixin and its analogue,DHP,afforded no protection against Aβ-induced cell death.SAC afforded no protection against HNE- and TFD-induced cell death,which has been shown to be mediated by caspase-3 dependent pathway.These results suggest that SAC protect against the neuronal cell death that is triggered by ER dysfunction. 相似文献
20.
骆庆和 《中国药理学与毒理学杂志》2012,(3):435
Amyloid beta(Aβ) is the primary constituent of plaque seen in Alzheimer’s disease.APP/PS1 mice,which possess the human APP/PS1 mutation,have been shown to demonstrate both Aβ plaque pathology and memory deficits in behavioral task.While SAMP8 mice are the strain of animal exhibiting age-related pathological changes in the brain and deficit in learning and memory.We crossed APP/PS1 mice with SAMP8 strain mice and generated AD model(P8-APP/PS1) mice expressing human APP/PS1 gene in SAMP8 background.To characterize the P8-APP/PS1 model,behavioral evaluations in a full of sensorimotor,anxiety,and cognitive tasks were conducted in the new strain mice with same ages of C57 wild,C57 APP/PS1 and SAMP8 wild mice serving as control groups.At the ages of 3,6 and 9 months,P8-APP/PS1 mice exhibited greater open field activity than C57 APP/PS1.The elevated plus maze experiment showed that P8-APP/PS1 mouse spent more time in open arm compared with C57 APP/PS1.The learning memory ability was measured by applying shuttle box and Morris water maze.At 9 months old,the learning and memory deficit was found in P8-APP/PS1 mice,but there was not in control groups.To further evaluate the pathological changes,beta amyloid immunohistochemistry was performed and dense APP deposit was observed at the earlier life time as 6 months in P8-APP/PS1,but not in control groups.Moreover,APP deposit in P8-APP/PS1 was aggravated and most severe compared to other groups at 9 months old.Induced APP/PS1 into SAMP8 strain exacerbated cognitive impairment and accelerated APP deposition at an early age in SAMP8 life.Thus,P8-APP/PS1 model could be considered as a more relevant AD model for the AD research. 相似文献