Orally Administered Melatonin Prevents Lipopolysaccharide-Induced Neural Tube Defects in Mice

Lipopolysaccharide (LPS) has been associated with adverse pregnant outcomes, including fetal demise, intra-uterine growth restriction (IUGR), neural tube defects (NTDs) and preterm delivery in rodent animals. Previous studies demonstrated that melatonin protected against LPS-induced fetal demise, IUGR and preterm delivery. The aim of the present study was to investigate the effects of melatonin on LPS-induced NTDs. All pregnant mice except controls were intraperitoneally injected with LPS (25 µg/kg) daily from gestational day (GD)8 to GD12. Some pregnant mice were orally administered with melatonin (MT, 50 mg/kg) before each LPS injection. A five-day LPS injection resulted in 27.5% of fetuses with anencephaly, exencephaly or encephalomeningocele. Additional experiment showed that maternal LPS exposure significantly down-regulated placental proton-coupled folate transporter (pcft) and disturbed folate transport from maternal circulation through the placentas into the fetus. Interestingly, melatonin significantly attenuated LPS-induced down-regulation of placental pcft. Moreover, melatonin markedly improved the transport of folate from maternal circulation through the placentas into the fetus. Correspondingly, orally administered melatonin reduced the incidence of LPS-induced anencephaly, exencephaly or encephalomeningocele. Taken together, these results suggest that orally administered melatonin prevents LPS-induced NTDs through alleviating LPS-induced disturbance of folate transport from maternal circulation through the placenta into the fetus.     

Immune Response of Mice to Orally Administered Lactic Acid Bacteria

In order to elucidate the interaction of lactic acid bacteria with the immune system, immune responses to the lactic acid bacteria, Bifidobacterium longum and Lactobacillus acidophilus, were examined in mice fed with each organism. In mice fed with B. longum for more than 8 weeks, an antibody response was detected to the cytoplasm of B. longum, but not to the cell wall. On the other hand, in mice fed with L. acidophilus for more than 6 weeks, an antibody response was detected to both the cytoplasm and cell wall of L. acidophilus. Moreover, feeding each organism for 2 weeks enhanced the proliferative response of Peyer’s patch (PP) cells to the cell fraction against which the serum antibody was detected. However, this was not found with spleen cells. These results suggest that mucosal stimulation by lactic acid bacteria may induce a systemic immune response to them.     

Effects of Orally Administered Bovine Lactoperoxidase on Dextran Sulfate Sodium-Induced Colitis in Mice

The effect of lactoperoxidase (LPO) on dextran sulfate sodium-induced colitis was examined in mice. After 9 d of colitis induction, weight loss, colon shortening, and the histological score were significantly suppressed in mice orally administered LPO (62.5 mg/body/d) as compared to a group administered bovine serum albumin. These results suggest that LPO exhibits anti-inflammatory effects in the gastrointestinal tract.     

Dysfunction of astrocytes in senescence-accelerated mice SAMP8 reduces their neuroprotective capacity

Early onset increases in oxidative stress and tau pathology are present in the brain of senescence-accelerated mice prone (SAMP8). Astrocytes play an essential role, both in determining the brain's susceptibility to oxidative damage and in protecting neurons. In this study, we examine changes in tau phosphorylation, oxidative stress and glutamate uptake in primary cultures of cortical astrocytes from neonatal SAMP8 mice and senescence-accelerated-resistant mice (SAMR1). We demonstrated an enhancement of abnormally phosphorylated tau in Ser(199) and Ser(396) in SAMP8 astrocytes compared with that of SAMR1 control mice. Gsk3beta and Cdk5 kinase activity, which regulate tau phosphorylation, was also increased in SAMP8 astrocytes. Inhibition of Gsk3beta by lithium or Cdk5 by roscovitine reduced tau phosphorylation at Ser(396). Moreover, we detected an increase in radical superoxide generation, which may be responsible for the corresponding increase in lipoperoxidation and protein oxidation. We also observed a reduced mitochondrial membrane potential in SAMP8 mouse astrocytes. Glutamate uptake in astrocytes is a critical neuroprotective mechanism. SAMP8 astrocytes showed a decreased glutamate uptake compared with those of SAMR1 controls. Interestingly, survival of SAMP8 or SAMR1 neurons cocultured with SAMP8 astrocytes was significantly reduced. Our results indicate that alterations in astrocyte cultures from SAMP8 mice are similar to those detected in whole brains of SAMP8 mice at 1-5 months. Moreover, our findings suggest that this in vitro preparation is suitable for studying the molecular and cellular processes underlying early aging in this murine model. In addition, our study supports the contention that astrocytes play a key role in neurodegeneration during the aging process.     

Effects of Orally Administered Bovine Lactoferrin on the Faecal Enterobacteriaceae of SPF Mice Fed Milk

Several phytotoxic metabolites, including a novel compound chaetoglobosin O, were isolated from Cylindrocladium floridanum Sobers et Seymore. The structure of chaetoglobosin O, including its absolute configuration, was determined by a spectroscopic analysis and chemical correlation. Purified chaetoglobosins A, C, and O showed potent growth-inhibition activity against alfalfa seedlings.     

Chimeric Plant Virus Particles Administered Nasally or Orally Induce Systemic and Mucosal Immune Responses in Mice

The humoral immune responses to the D2 peptide of fibronectin-binding protein B (FnBP) of Staphylococcus aureus, expressed on the plant virus cowpea mosaic virus (CPMV), were evaluated after mucosal delivery to mice. Intranasal immunization of these chimeric virus particles (CVPs), either alone or in the presence of ISCOM matrix, primed CPMV-specific T cells and generated high titers of CPMV- and FnBP-specific immunoglobulin G (IgG) in sera. Furthermore, CPMV- and FnBP-specific IgA and IgG could also be detected in the bronchial, intestinal, and vaginal lavage fluids, highlighting the ability of CVPs to generate antibody at distant mucosal sites. IgG2a and IgG2b were the dominant IgG subclasses in sera to both CPMV and FnBP, demonstrating a bias in the response toward the T helper 1 type. The sera completely inhibited the binding of human fibronectin to the S. aureus FnBP. Oral immunization of the CVPs also generated CPMV- and FnBP-specific serum IgG; however, these titers were significantly lower and more variable than those generated by the intranasal route, and FnBP-specific intestinal IgA was undetectable. Neither the ISCOM matrix nor cholera toxin enhanced these responses. These studies demonstrate for the first time that recombinant plant viruses have potential as mucosal vaccines without the requirement for adjuvant and that the nasal route is most effective for the delivery of these nonreplicating particles.Replicating vaccines such as live-attenuated bacterial (13) and virus (36, 40, 45) vaccines, as well as naked DNA vaccines (31), induce stronger and longer-lasting immune responses than conventional killed-subunit vaccines and also elicit protective cell-mediated immunity, often without the need for adjuvant. There are however, safety concerns over the use of these vaccines (24, 49), where persistence or reversion to virulence of the live vaccine strains and integration of the naked DNA vaccine into the host chromosome are of major concern. Recent technological advances, such as the use of more-effective adjuvants for both mucosal and systemic delivery (12, 16), liposome and ISCOM encapsulation of proteins and peptides (3, 19, 27), multiple antigenic peptides (35), and virus-like particles (VLPs) (1), have led to the development of more-effective subunit vaccines. To circumvent the safety concerns of replicating vaccines and to avoid the need for peptide synthesis and chemical coupling to a carrier such as keyhole limpet hemocyanin, we have been examining the utility of the plant virus cowpea mosaic virus (CPMV) as a carrier of peptides for immune recognition. CPMV is composed of 2 subunits, the small (S) and large (L) coat proteins, of which there are 60 copies of each per virus particle (46). Foreign peptides up to 37 amino acids in length can be expressed on either the L or S proteins; hence, 60 to 120 copies of a peptide can be displayed on a single virus particle (4b, 34). A peptide from the human immunodeficiency virus (HIV) gp41 glycoprotein is highly immunogenic when displayed on CPMV, eliciting high titers of HIV neutralizing antibodies (28, 29). Furthermore, a peptide derived from the VP2 protein of canine parvovirus (CPV) expressed on CPMV is immunogenic when administered to mink and subsequently protected the mink from a lethal challenge with the CPV-related mink enteritis virus (10).Most infectious viral and bacterial diseases involve colonization or invasion through mucosal surfaces by the pathogen, and hence it is important to develop vaccines that induce strong protective mucosal immune responses as a first line of defense. Where the organism, such as Vibrio cholerae and enterotoxigenic Escherichia coli, is restricted to the mucosa, strong mucosal immunity is often sufficient. However, when the organism disseminates from the mucosa into the bloodstream, a strong systemic response is also required to engender sterile immunity. Hence, the ideal mucosal vaccine should generate local immune responses at mucosal surfaces but also elicit generalized vaccine-specific immunity in the systemic lymphoid organs. The potential of CPMV-based vaccines for mucosal vaccination has not previously been determined.Oral immunization with particulate antigens, especially when presented as viable organisms, which can colonize the mucosa better than killed organisms, is effective at inducing local and generalized secretory and systemic immune responses (5, 43). However, the acidic pH and the presence of degradative enzymes in the gastrointestinal tract mean that when nonreplicating antigens are used, high concentrations are often required to elicit high levels of immunity (6). Another way to elicit mucosal immunity but circumvent the problems of oral immunization is to vaccinate via the intranasal route (2). Intranasal immunization requires up to 10-fold less immunogen for effective immunization and avoids the problems of low pH. Live vaccines (15, 37), virus-like particles (4, 25, 32), and synthetic peptides (17, 33, 44) in the absence of adjuvant have been shown to stimulate strong immunity when administered by this route. Furthermore, stimulation of the nasal mucosa, like stimulation of the intestinal mucosa, has been shown to be effective at generating protective immunity at distant mucosal sites (reviewed in reference 2).To assess the potential of CVPs as mucosal vaccines, mice were immunized intranasally or orally with CPMV expressing a peptide derived from the fibronectin-binding protein B (FnBP) D2 motif of Staphylococcus aureus (14, 42). The three fibronectin-binding domains, termed D1, D2, and D3, of FnBP have been shown to be immunogenic in mice and rats (7, 41). The CVPs were shown to be more immunogenic when administered (without adjuvant) via the intranasal route than when administered by the oral route, generating high titers of D2-specific antibody in serum and mucosa, and the serum antibody inhibited fibronectin binding to FnBP.     

The Hippocampal Proteomic Analysis of Senescence-Accelerated Mouse: Implications of Uchl3 and Mitofilin in Cognitive Disorder and Mitochondria Dysfunction in SAMP8

Senescence-accelerated mouse prone 8 (SAMP8) is considered as a useful animal model for age-related learning and memory impairments. Hippocampus, a critical brain region associated with cognitive decline during normal aging and various neurodegenerative diseases, appeared a series of abnormalities in SAMP8. To investigate the molecular mechanisms underlying age-related cognitive disorders, we used 2-DE coupled with MALDI TOF/TOF MS to analyze the differential protein expression of the hippocampus of SAMP8 at 6-month-old compared with the age-matched SAM/resistant 1 (SAMR1) which shows normal aging process. Two proteins were found to be markedly changed in SAMP8 as compared to SAMR1: ubiquitin carboxyl-terminal hydrolase L3 (Uchl3), implicating in cytosolic proteolysis of oxidatively damaged proteins, was down-regulated while mitofilin, a vital protein for normal mitochondria function, exhibited four isoforms with a consistent basic shift of isoelectric point among the soluble hippocampal proteins in SAMP8 compared with SAMR1. The alterations were confirmed by Western blotting analysis. The analysis of their expression changes may shed light on the mechanisms of learning and memory deficits and mitochondrial dysfunction as observed in SAMP8.     

Senescence-Accelerated Mouse (SAM) with Special References to Neurodegeneration Models,SAMP8 and SAMP10 Mice

The SAM strains, a group of related inbred strains consisting of senescence-prone inbred strains (SAMP) and senescence-resistant inbred strains (SAMR), have been successfully developed by selective inbreeding of the AKR/J strain of mice donated by the Jackson laboratory in 1968. The characteristic feature of aging common to the SAMP and SAMR is accelerated senescence and normal aging, respectively. Furthermore, SAMP and SAMR strains of mice manifest various pathobiological phenotypes spontaneously. Among SAMP strains, SAMP8 and SAMP10 mice show age-related behavioral deterioration such as deficits in learning and memory, emotional disorders (reduced anxiety-like behavior and depressive behavior) and altered circadian rhythm associated with certain pathological, biochemical and pharmacological changes. Here, the previous and recent literature on SAM mice are reviewed with an emphasis on SAMP8 and SAMP10 mice. A spontaneous model like SAM with distinct advantages over the gene-modified model is hoped by investigators to be used more widely as a biogerontological resource to explore the etiopathogenesis of accelerated senescence and neurodegenerative disorders.     

Teratogenicity and Embryotoxicity of Orally Administered Fenchlorphos in Blue Foxes

Pregnant blue foxes (Alopex lagopus) were administered fenchlorphos (0-0-dimethyl-0-(2,4,5-trichlorophenyl) phos-phorothioate) orally at a dose of 100 mg/kg/day in different periods of gestation. The dose chosen represents the therapeutic dose for the treatment of parasitic lesions. At term the mean number of whelps were recorded, and they were killed and examined for external, visceral and skeletal malformations. Of 19 medicated vixens the mean number of live whelps at term was 1.2 per vixen versus 9.5 in the control group. There was an evident predominance of males in the medicated groups. Several malformations of the head were registered, among them incomplete ossification of the skull bones, cleft palate, hydrocephalus internus and externus. Minor malformations like extra ribs or missing ribs occurred in the medicated groups. Congenital alopecia, hypoplastic kidneys, and hydronephrosis were observed in all the whelps in 1 medicated group. No significant difference in total brain weight, cerebellum weight or the cerebellum-to-total-brain weight was observed. Histological examination of the cerebellum showed a narrowing or absence of the granular and the molecular layers of the cortical zone.     

Effects of Hydrogen-Rich Saline on Hepatectomy-Induced Postoperative Cognitive Dysfunction in Old Mice

This study aims to investigate the protective effects and underlying mechanisms of hydrogen-rich saline on the cognitive functions of elder mice with partial hepatectomy-induced postoperative cognitive dysfunction (POCD). Ninety-six old male Kunming mice were randomly divided into 4 groups (n?=?24 each): control group (group C), hydrogen-rich saline group (group H), POCD group (group P), and POCD?+?hydrogen-rich saline group (group PH). Cognitive function was subsequently assessed using Morris water-maze (MWM) test. TNF-α and IL-1β levels were measured by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry, along with NF-κB activity determined by ELISA. The morphology of hippocampal tissues were further observed by HE staining. Learning and memory abilities of mice were significantly impaired at day 10 and day 14 post-surgery, as partial hepatectomy significantly prolonged the escape latency, decreased time at the original platform quadrant and frequency of crossing in group P when compared to group C (p?<?0.05). The surgery also increased the contents of TNF-α, IL-1β, and NF-κB activity at all time points after surgery (p?<?0.05). The introduction of hydrogen-rich saline (group PH) partially rescued spatial memory and learning as it shortened escape latency and increased time and crossing frequency of original platform compared to group P (p?<?0.05). Moreover, such treatment also decreased TNF-α and IL-1β levels and NF-κB activity (p?<?0.05). In addition, cell necrosis in the hippocampus induced by hepatectomy was also rescued by hydrogen-rich saline. Hydrogen-rich saline can alleviate POCD via inhibiting NF-κB activity in the hippocampus and reducing inflammatory response.     

The Brewed Rice Vinegar Kurozu Increases HSPA1A Expression and Ameliorates Cognitive Dysfunction in Aged P8 Mice

Kurozu is a traditional Japanese rice vinegar. During fermentation and aging of the Kurozu liquid in an earthenware jar over 1 year, a solid residue called Kurozu Moromi is produced. In the present study, we evaluated whether concentrated Kurozu or Kurozu Moromi could ameliorate cognitive dysfunction in the senescence-accelerated P8 mouse. Senescence-accelerated P8 mice were fed 0.25% (w/w) concentrated Kurozu or 0.5% (w/w) Kurozu Moromi for 4 or 25 weeks. Kurozu suppressed cognitive dysfunction and amyloid accumulation in the brain, while Kurozu Moromi showed a tendency to ameliorate cognitive dysfunction, but the effect was not significant. We hypothesize that concentrated Kurozu has an antioxidant effect; however, the level of lipid peroxidation in the brain did not differ in senescence-accelerated P8 mice. DNA microarray analysis indicated that concentrated Kurozu increased HSPA1A mRNA expression, a protein that prevents protein misfolding and aggregation. The increase in HSPA1A expression by Kurozu was confirmed using quantitative real-time PCR and immunoblotting methods. The suppression of amyloid accumulation by concentrated Kurozu may be associated with HSPA1A induction. However, concentrated Kurozu could not increase HSPA1A expression in mouse primary neurons, suggesting it may not directly affect neurons.     

通心络治疗与SAMP8早期脑内淀粉样病变改善的相关性研究

目的:研究中药通心络(TXL)与治疗SAMP8小鼠早期脑内淀粉样病理变化改善的相关性.方法:取4月龄雄性SAMP8小鼠,随机分为6组:SAMP8(空白对照)组、石杉碱甲(阳性对照)组、TXL低剂(治疗)组、TXL中剂(治疗)组、TXL高剂(治疗)组、SAMR1(对照)组,每组15只.于第八周末,检测海马神经元染色质聚缩情况、皮质和海马耱原沉积情况、脑内淀粉样物质沉积情况、小鼠皮质Aβ 1-42寡聚体的水平.结果:(1)HE染色结果显示SAMP8组有明显的核深染现象,通心络治疗组有改善;(2)与SAMP8对照组相比,TXL中剂组、TXL高剂组淀粉样沉积均有显著性差异(P＜0.01);(3)与SAMP8组相比,TXL低剂组(P＜0.05)、TXL中剂组(P＜0.01)和TXL高剂组(P＜0.05)PAS阳性颗粒(acid-Schiff(PAS)-positive granular structures,PGS)显著减少;(4)与SAMP8相比,TXL各治疗组Aβ 42寡聚体水平均有显著性降(P＜0.01);(5)TXL治疗剂量与淀粉样沉积、糖原沉积具有相关性,TXL中剂量治疗即可达到改善的效果,而Aβ 42寡聚体聚集水平与TXL剂量有显著的线性负相关(r=-0.856,P＜0.01).结论:通心络治疗能够明显改善SAMP8小鼠早期脑内淀粉样病变.     

Continuous Orally Administered Coffee Enhanced the Antigen-Specific Th1 Response and Reduced Allergic Development in a TCR-Transgenic Mice Model

Coffee is a globally consumed beverage. Although recent studies have suggested that coffee reduced the risk of lifestyle-related diseases, there are few studies regarding allergic response.

This study investigates the effects of orally administered coffee (91 ml/kg/d) on allergic responses using a T cell receptor (TCR)-transgenic DO11.10 mouse allergic model. Splenocytes from coffee-administered naïve mice increased antigen (Ag)-specific interleukin (IL)-12p40 secretion. When Ag sensitization and coffee administration were concurrently performed, the splenocytes from coffee-administered mice showed a decrease of IL-2 and an increase of IL-12p40 secretion. The Ag-specific cutaneous response and serum IgE level were reduced in coffee-administered mice, although, after establishing the allergy, coffee administration did not suppress the allergic reaction.

These results suggest that coffee could induce a Th1-type response of the immune system and prevent an allergy developing. Further studies on the optimum dose, cultivar differences, and roasted degree need to be undertaken.     

Intermittent Hypoxia Can Aggravate Motor Neuronal Loss and Cognitive Dysfunction in ALS Mice

Background

Patients with ALS may be exposed to variable degrees of chronic intermittent hypoxia. However, all previous experimental studies on the effects of hypoxia in ALS have only used a sustained hypoxia model and it is possible that chronic intermittent hypoxia exerts effects via a different molecular mechanism from that of sustained hypoxia. No study has yet shown that hypoxia (either chronic intermittent or sustained) can affect the loss of motor neurons or cognitive function in an in vivo model of ALS.

Objective

To evaluate the effects of chronic intermittent hypoxia on motor and cognitive function in ALS mice.

Methods

Sixteen ALS mice and 16 wild-type mice were divided into 2 groups and subjected to either chronic intermittent hypoxia or normoxia for 2 weeks. The effects of chronic intermittent hypoxia on ALS mice were evaluated using the rotarod, Y-maze, and wire-hanging tests. In addition, numbers of motor neurons in the ventral horn of the spinal cord were counted and western blot analyses were performed for markers of oxidative stress and inflammatory pathway activation.

Results

Compared to ALS mice kept in normoxic conditions, ALS mice that experienced chronic intermittent hypoxia had poorer motor learning on the rotarod test, poorer spatial memory on the Y-maze test, shorter wire hanging time, and fewer motor neurons in the ventral spinal cord. Compared to ALS-normoxic and wild-type mice, ALS mice that experienced chronic intermittent hypoxia had higher levels of oxidative stress and inflammation.

Conclusions

Chronic intermittent hypoxia can aggravate motor neuronal death, neuromuscular weakness, and probably cognitive dysfunction in ALS mice. The generation of oxidative stress with activation of inflammatory pathways may be associated with this mechanism. Our study will provide insight into the association of hypoxia with disease progression, and in turn, the rationale for an early non-invasive ventilation treatment in patients with ALS.     

Intestinal Distribution and Intraluminal Localization of Orally Administered Clostridium butyricum in Rats

Clostridium butyricum has been used as a probiotic in animals and humans for years, however, its fate in the intestine has not been clarified yet. We investigated the intestinal fate of C. butyricum using a selective medium and a monoclonal antibody after orally administering C. butyricum spores to rats. The number of C. butyricum, both viable and dead cells, in the intestinal contents were counted by enzyme-linked immunosorbent assay (ELISA) at various times after a single oral administration. The total viable number of C. butyricum was counted using a selective medium, and viable resting spores were selectively detected by treating the samples with ethanol. To investigate the intraluminal localization of the C. butyricum cells, frozen intestinal tracts were imprinted onto slides and stained with immunogold-silver. Total viable spores exceeded the number of viable resting spores by more than 10-fold from the proximal to middle of the small intestine 30 min after administration. Vegetative cells of C. butyricum were first detected in the distal small intestine after 2 hr, and vegetative growth was observed from the cecum to the colon 5 hr after administration. Dead vegetative cells were detected 9 hr after administration, and C. butyricum cells were not detected in the intestine after 3 days. The C. butyricum cells in the intestinal imprints were stained specifically by immunogold-silver staining, and proliferative cells were observed in the cecum after 3 hr. These results suggest that the administered C. butyricum germinated in the upper small intestine, grew mainly from the distal small intestine to the colon and were excreted from the rat intestine within 3 days.     

Immature Persimmon Suppresses Amyloid Beta (Aβ) Mediated Cognitive Dysfunction via Tau Pathology in ICR Mice

This study confirmed the ameliorating effect of immature persimmon (Diospyros kaki) ethanolic extract (IPEE) on neuronal cytotoxicity in amyloid beta (Aβ)_1–42-induced ICR mice. The administration of IPEE ameliorated the cognitive dysfunction in Aβ_1–42-induced mice by improving the spatial working memory, the short-term and long-term memory functions. IPEE protected the cerebral cholinergic system, such as the acetylcholine (ACh) level and acetylcholinesterase (AChE) activity, and antioxidant system, such as the superoxide dismutase (SOD), reduced glutathione (GSH) and malondialdehyde (MDA) contents. In addition, mitochondrial dysfunction against Aβ_1–42-induced toxicity was reduced by regulating the reactive oxygen species (ROS), mitochondrial membrane potential and ATP contents. In addition, IPEE regulated the expression levels of tau signaling, such as TNF-α, p-JNK, p-Akt, p-GSK3β, p-tau, p-NF-κB, BAX and caspase 3. Finally, gallic acid, ellagic acid and quercetin 3-O-(6″-acetyl-glucoside) were identified as the physiological compounds of IPEE using ultra-performance liquid chromatography ion mobility separation quadrupole time-of-flight/tandem mass spectrometry (UPLC IMS Q-TOF/MS²).     

电针对SAMP8小鼠海马区PS1蛋白表达的影响

目的:研究电针对于SAMP8模型小鼠海马区早老蛋白1(presenilian 1,PS1)表达的影响,探讨电针治疗阿尔兹海默病(AD)的作用机制。方法:将20只SAMP8小鼠(早老化小鼠)随机分为模型对照组、电针治疗组,每组10只;10只SAMR1小鼠(正常老化小鼠)组成正常对照组。正常对照组和模型对照组正常饲养15天,在电针治疗组治疗时抓取束缚一次,不做任何治疗;电针治疗组每天治疗前抓取束缚之后再进行电针治疗,治疗穴位选取"百会"、"印堂"、"人中"三穴,频率2 Hz,电流强度以小鼠头部微颤为宜,留针20 min,每日1次,共15天。电针治疗结束后,通过Morris水迷宫实验观察小鼠的行为学变化;通过免疫组化观察SAMP8小鼠海马区PS1蛋白表达情况;通过Western blot方法检测各组海马区的PS1蛋白表达水平。结果:行为学中Morris水迷宫检测显示:模型组与正常对照组比较逃避潜伏时增加,空间探索实验穿越平台次数和平台象限游泳时间明显减少(P0.05,P0.01);电针治疗组逃避潜伏时明显减少,空间探索实验穿越平台次数和平台象限游泳时间明显增加(P0.05);免疫组化观察各组海马区PS1蛋白表达,电针治疗组较模型组明显降低;Western blot结果显示PS1蛋白在海马区表达水平,模型组高于正常对照组(P0.01),而电针治疗组低于模型组(P0.01)。结论:电针可以改善小鼠的学习记忆能力,而且电针治疗组海马区PS1蛋白含量明显低于模型组,电针治疗可能参与减弱PS1蛋白的表达,降低Aβ水平,对于AD治疗有益。