Morris Maze Test Research Articles

Design and preparation of NMN nanoparticles based on protein-marine polysaccharide with increased NAD+ level in D-galactose induced aging mice model

Nicotinamide mononucleotide (NMN) is being investigated for its ability to address the decline in NAD+ level during aging. This study aimed to construct a delivery system based on ovalbumin and fucoidan nanoparticles to ameliorate the bioaccessibility of NMN by increasing NAD+ level in aging mouse model. The NMN-loaded ovalbumin and fucoidan nanoparticles (OFNPs) were about 177 nm formed by the interplay of hydrogen bonds between ovalbumin and fucoidan. Compared with free NMN, NMN-loaded OFNPs intervention could obviously improve the antioxidant enzyme activity of senescent cell induced by D-galactose. The NMN-loaded OFNPs treatment could ameliorate the loss of weight and organ index induced by senescence, and maintain the water content for the aging mice. The Morris maze test indicated that hitting blind side frequency and escape time of NMN-loaded OFNPs group decreased by 13% and 35% compared with that of free NMN group. Furthermore, the NMN-loaded OFNPs significantly alleviated the age-related oxidative stress and increased the generation of NAD+ 1.34 times by improving the bioaccessibility of NMN. Our data in this study supplied a strategy to enhance the bioavailability of NMN in senescence treatment.

Sulphated Fucooligosaccharide from Sargassum Horneri: Structural Analysis and Anti-Alzheimer Activity.

In the present study, sulfated polysaccharides were obtained by digestion of Sargassum horneri and preparation with enzyme-assisted extraction using three food-grade enzymes, and their anti- Alzheimer's activities were investigated. The results demonstrated that the crude sulfated polysaccharides extracted using AMGSP, CSP and VSP dose-dependently (25-100µg·mL- 1) raised the spontaneous alternating manner (%) in the Y maze experiment of mice and reduced the escape latency time in Morris maze test. AMGSP, CSP and VSP also exhibited good anti-AChE and moderate anti-BuChE activities. CSP displayed the best inhibitory efficacy against AChE. with IC50 values of 9.77 µM. And, CSP also exhibited good inhibitory selectivity of AChE over BuChE. Next, CSP of the best active crude extract was separated by the preparation type high performance liquid phase to obtain the sulphated fucooligosaccharide section: SFcup (→3-α-L-fucp(2-SO3-)-1→4-α-L-fucp(2,3-SO3-)-1→section), SFcup showed a best inhibitory efficacy against AChE with IC50 values of 4.03 µM. The kinetic research showed that SFcup inhibited AChE through dual binding sites. Moreover, the molecular docking of SFcup at the AChE active site was in accordance with the acquired pharmacological results.

Exercise combined with postbiotics treatment results in synergistic improvement of mitochondrial function in the brain of male transgenic mice for Alzheimer’s disease

BackgroundIt has been suggested that exercise training and postbiotic supplement could decelerate the progress of functional and biochemical deterioration in double transgenic mice overexpresses mutated forms of the genes for human amyloid precursor protein (APPsw) and presenilin 1 (m146L) (APP/PS1TG). Our earlier published data indicated that the mice performed better than controls on the Morris Maze Test parallel with decreased occurrence of amyloid-β plaques in the hippocampus. We investigated the neuroprotective and therapeutic effects of high-intensity training and postbiotic supplementation.MethodsThirty-two adult APP/PS1TG mice were randomly divided into four groups: (1) control, (2) high-intensity training (3) postbiotic, (4) combined (training and postbiotic) treatment for 20 weeks. In this study, the whole hemibrain without hippocampus was used to find molecular traits explaining improved brain function. We applied qualitative RT-PCR for gene expression, Western blot for protein level, and Zymography for LONP1 activity. Disaggregation analysis of Aβ-40 was performed in the presence of Lactobacillus acidophilus and Bifidobacterium longum lysate.ResultsWe found that exercise training decreased Alzheimer’s Disease (AD)-related gene expression (NF-kB) that was not affected by postbiotic treatment. The preparation used for postbiotic treatment is composed of tyndallized Bifidobacterium longum and Lactobacillus acidophilus. Both of the postbiotics effectively disaggregated amyloid-β/Aβ-40 aggregates by chelating Zn2+ and Cu2+ ions. The postbiotic treatment decreased endogenous human APPTG protein expression and mouse APP gene expression in the hemibrains. In addition, the postbiotic treatment elevated mitochondrial LONP1 activity as well.ConclusionOur findings revealed distinct mechanisms behind improved memory performance in the whole brain: while exercise training modulates NF-kB signaling pathway regulating immune response until postbiotic diminishes APP gene expression, disaggregates pre-existing amyloid-β plaques and activates mitochondrial protein quality control in the region of brain out of hippocampus. Using the above treatments complements and efficiently slows down the development of AD.

Voluntary exercise does not increase gastrointestinal motility but increases spatial memory, intestinal eNOS, Akt levels, and Bifidobacteria abundance in the microbiome.

The interaction between the gut and brain is a great puzzle since it is mediated by very complex mechanisms. Therefore, the possible interactions of the brain-exercise-intestine-microbiome axis were investigated in a control (C, N = 6) and voluntarily exercised (VE, N = 8) middle-aged rats. The endurance capacity was assessed by VO2max on the treadmill, spatial memory by the Morris maze test, gastrointestinal motility by EMG, the microbiome by 16S RNA gene amplicon sequencing, caveolae by electron microscopy, and biochemical assays were used to measure protein levels and production of reactive oxygen species (ROS). Eight weeks of voluntary running increased VO2max, and spatial memory was assessed by the Morris maze test but did not significantly change the motility of the gastrointestinal tract or production of ROS in the intestine. The protein kinase B (Akt) and endothelial nitric oxide synthase (eNOS) protein levels significantly increased in the intestine, while peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), mitochondrial transcription factor A (TFAM), nuclear respiratory factor 1 (NFR1), SIRT1, SIRT3, nicotinamide phosphoribosyl transferase (NAMPT), and nuclear factor κB (NF-κB) did not change. On the other hand, voluntary exercise increased the number of caveolae in the smooth muscles of the intestine and relative abundance of Bifidobacteria in the microbiome, which correlated with the Akt levels in the intestine. Voluntary exercise has systemic effects and the relationship between intestinal Akt and the microbiome of the gastrointestinal tract could be an important adaptive response.

Study on Undercarboxylated Osteocalcin in Improving Cognitive Function of Rats with Type 2 Diabetes Mellitus by Regulating PI3K-AKT-GSK/3β Signaling Pathwaythrough medical images

ABSTRACT This paper aims to clarify the effect of Undercarboxylated osteocalcin (ucOC) on cognitive function in rats with type 2 diabetes mellitus (T2DM). This research reviewed the cognitive function of 35 diabetic patients, 33 non-diabetic patients and the serum levels of Undercarboxylated osteocalcin (ucOC) in patients. What’s more, we analyzed the correlation between serum ucOC levels and cognitive function. Diabetic rats were treated with high (30 μg·kg−1·d−1) and low (10 μg·kg−1·d−1) doses of ucOC to investigate its effects in regulating ucOC on blood lipid, blood glucose and cognitive function. We systematically detected the phosphorylation levels of cognitive level-related proteins (PI3K, AKT, and GSK/3β) in the hippocampus by Western Blot. Finally, PI3K-Akt pathway involved in regulating cognitive function in diabetic rats by ucOC was verified with AKT pathway inhibitor LY294002. MoCA score and serum ucOC levels were significantly reduced in patients with diabetes mellitus. ucOC could concentration-dose-dependently decrease the blood glucose and lipid levels, and improve glucose metabolism and weaken insulin resistance in diabetic rats (P < 0.001). In addition, escape latency in diabetic rats was significantly higher than that of normal rats in the Morris maze test, and ucOC dose-dependently shortened the escape latency in diabetic rats (all with P < 0.05). After using AKT pathway inhibitor, ucOC failed to shorten the escape latency in diabetic rats. In conclusion, this study explored the relevant mechanisms in inducing cognitive dysfunction of T2DM, suggesting the potential value of ucOC as a drug to improve cognitive dysfunction in patients with T2DM in clinical.

ВЛИЯНИЕ N-(4-АЦЕТОКСИБЕНЗОИЛ)ГЛИЦИНАТА КАЛИЯ НА СЕНСОРНО-МОТОРНЫЕ И КОГНИТИВНЫЕ НАРУШЕНИЯ В УСЛОВИЯХ ЭКСПЕРИМЕНТАЛЬНОЙ ХРОНИЧЕСКОЙ ИШЕМИИ ГОЛОВНОГО МОЗГА

The effect of a new conjugate of hydroxybenzoic acid with glycine on sensory-motor and cognitive impairments in experimental animals with chronic cerebrovascular insufficiency (CCI) was studied. CCI was modeled in rats by stenosis of thelumen of the carotid arteries in 60 %. 40 days after the operation, experimental groups were formed and the test compound was administered for 14 days. Citicoline was used as a reference drug, and saline was administered as placebo. After treatment with the Rotarod, Adhesion Test, Novel Object Recognition (NOR), and Morris Water Maze tests, the severity of sensory-motor and cognitive impairments was assessed. It was noted that in animals with CCI with placebo treatment, the pathology was accompanied by a pronounced impairment of coordination and sensory-motor function of the forelimbs, as wellas cognitive impairments (impaired short-term and long-term memory in the NOR and the Morris maze tests). The course introduction of anew conjugate of hydroxybenzoic acid with glycine contributed to a significant improvement in sensory-motor and cognitive functions in animals with CCI. The noted neuroprotective effect was comparable to that of the reference drug citicoline.

The neuroprotective effect of Xylopia parviflora against aluminum chloride-induced neurotoxicity in rats

Neurodegenerative disease such as Alzheimer’s disease, are progressive disorders which has been linked to oxidative imbalance and associated perturbations characterised by loss of memory, cognition and cholinergic deficit. To date, cholinesterase inhibition and neuroprotection are the two major strategies in drug development. Xylopia parviflora (Annonacea family) is a spice consumed in Cameroon and has been used in traditional medicine to treat various pains. In this study, X. parviflora was evaluated on behavioural studies, ion homeostasis, cholinesterase inhibitory and antioxidant activities. Rats were exposed to aluminium chloride (75 mg/kg) during 60 days, and were treated with the extract of X. parviflora (150 and 300 mg/kg BW) and two drugs references (Donepezil and Curcumin). Behavioural parameters were assessed using the Morris-Maze test and the Open Field, followed by biochemical investigations, namely, cholinesterase enzyme activity (AChE and BChE), oxidative stress (NO, MDA, GSH level, SOD and Catalase activities) and ion homeostasis (Mg2+ and Ca2+ levels). AlCl3 administration shows a decrease in learning and memory improvement during behavioural studies, significant alteration of the central cholinergic system characterised by an increase in AChE and BChE activities to 2.72 ± 0.002 mol/min/g and 5.74 ± 0.12 mol/min/g respectively, disturbance of ion homeostasis with an increase in Ca2+ level (25.68 ± 3.78 μmol/mg protein) and a decrease in Mg2+ level (15.97 ± 2.05 μmol/mg protein) and an increase in oxidative stress compared to the positive control group. Treatment with the different doses of X. parviflora increased memory and improved locomotion, improved cholinesterase activities, ion homeostasis and stabilized brain oxidative stress levels. The study suggests that X. parviflora could potentially be used for the management of some biochemical alterations associated with Alzheimer’s disease. It could even be a good alternative to chemical drugs for neurotoxicity and memory enhancement.

A partial reduction of Drp1 improves cognitive behavior and enhances mitophagy, autophagy and dendritic spines in a transgenic Tau mouse model of Alzheimer disease.

The purpose of our study is to understand the impact of a partial dynamin-related protein 1 (Drp1) on cognitive behavior, mitophagy, autophagy and mitochondrial and synaptic activities in transgenic Tau mice in Alzheimer's disease (AD). Our laboratory reported increased levels of amyloid-beta (Aβ) and phosphorylated Tau (P-Tau) and reported that abnormal interactions between Aβ and Drp1, P-Tau and Drp1 induced increased mitochondrial fragmentation and reduced fusion and synaptic activities in AD. These abnormal interactions result in the proliferation of dysfunctional mitochondria in AD neurons. Recent research on mitochondria revealed that fission protein Drp1 is largely implicated in mitochondrial dynamics in AD. To determine the impact of reduced Drp1 in AD, we recently crossed transgenic Tau mice with Drp1 heterozygote knockout (Drp1+/-) mice and generated double mutant (P301LDrp1+/-) mice. In the current study, we assessed the cognitive behavior, mRNA and protein levels of mitophagy, autophagy, mitochondrial biogenesis, dynamics and synaptic genes, mitochondrial morphology and mitochondrial function and dendritic spines in Tau mice relative to double mutant mice. When compared with Tau mice, double mutant mice did better on the Morris Maze (reduced latency to find hidden platform, increased swimming speed and time spent on quadrant) and rotarod (stayed a longer period of time) tests. Both mRNA- and protein-level autophagy, mitophagy, mitochondrial biogenesis and synaptic proteins were increased in double mutant mice compared with Tau (P301L) mice. Dendritic spines were significantly increased; mitochondrial number was reduced and length was increased in double mutant mice. Based on these observations, we conclude that reduced Drp1 is beneficial in a symptomatic-transgenic Tau (P301L) mice.

Glibenclamide Ameliorates the Expression of Neurotrophic Factors in Sevoflurane Anaesthesia-induced Oxidative Stress and Cognitive Impairment in Hippocampal Neurons of Old Rats.

IntroductionSeveral antidiabetic medications have been proposed as prospective treatments for cognitive impairments in type 2 diabetes patients, glibenclamide (GBC) among them. Our research aimed to evaluate the impact of GBC on hippocampal learning memory and inflammation due to enhanced neurotrophic signals induced by inhalation of sevoflurane.Material and MethodsRats (Sprague Dawley, both sexes) were assigned to four groups: a control (vehicle, p.o.), GBC (10 mg/kg b.w.; p.o.), low-dose sevoflurane and low-dose sevoflurane + GBC (10 mg/kg b.w.; p.o.) for 23 days. Terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining was performed to analyse the count of apoptotic cells and ELISA was conducted to assess the protein signals. A Western blot, a Y-maze test, and a Morris maze test were performed, and the results analysed. Blood and tissues were collected, and isolation of RNA was performed with qRT-PCR.ResultsThe Morris maze test results revealed an improvement in the length of the escape latency on days 1 (P < 0.05), 2 (P < 0.01), 3, and 4 in the low-dose Sevo group. Time spent in the quadrant and crossing axis and the percentage of spontaneous alterations showed a substantial decrease in the low-dose Sevo group which received GBC at 10 mg/kg b.w. Significant increases were shown in IL-6 and TNF-α levels in the low-dose Sevo group, whereas a decrease was evident in the GBC group.ConclusionOur results indicate that glibenclamide may be a novel drug to prevent sevoflurane inhalation-induced impaired learning and reduce brain-derived neurotrophic factor release, which may be a vital target for the development of potential therapies for cognitive deficits and neurodegeneration.

Neuroprotective Effects of Fluoxetine on Molecular Markers of Circadian Rhythm, Cognitive Deficits, Oxidative Damage, and Biomarkers of Alzheimer's Disease-Like Pathology Induced under Chronic Constant Light Regime in Wistar Rats.

There is mounting evidence of circadian rhythm disruption in Alzheimer's disease (AD); however, the cause-and-effect relationship between them is not understood. Chronic constant light exposure effectively disrupts circadian rhythm in rats. On the basis of previous publications, we hypothesized that chronic constant light exposure might contribute significantly to development of AD-like-phenotype in rats and that fluoxetine (Flx) treatment might protect the brain against it. Adult male rats were exposed to normal light-dark cycles, constant light (LL), constant dark, and LL+Flx (5 mg/kg/day, ZT5) for four months. The expression of molecular markers of circadian rhythm: Per2 transcripts; and protein expression of peroxiredoxin-1 (PRX1) and hyperoxidized peroxiredoxins (PRX-SO2/3) were significantly dysregulated in the suprachiasmatic nuclei (SCN) of LL rats, which was prevented with concomitant fluoxetine administration. The levels of glutamate and γ-aminobutyric acid were dysregulated, and oxidative damage was observed in the SCN and hippocampi of LL rats. Fluoxetine treatment conferred protection against oxidative damage in LL rats. Constant light exposure also impaired rats' performance on Y-maze, Morris maze, and novel object recognition test, which was prevented with fluoxetine administration. A significant elevation in soluble Aβ1-42 levels, which strongly correlated with upregulation of Bace1 and Mgat3 transcripts was observed in the hippocampus of LL rats. Further, the expression of antiaging gene Sirt1 was downregulated, and neuronal damage indicator Prokr2 was upregulated in hippocampus. Fluoxetine rescued Aβ1-42 upregulation and AD-related genes' dysregulation. Our findings show that circadian disruption by exposure to chronic constant light may contribute to progression of AD, which can be prevented with fluoxetine treatment.

Effect of moxibustion on learning and memory in neonatal hypoxic-ischemia encephalopathy mice

To observe the effect of moxibustion on the expression of phosphorylated calcium/calmodulin-dependent protein kinase Ⅱα(pCaMKⅡα) and neuronal nuclei (NeuN) and the ability of learning and memory in the neonatal mice model of hypoxic-ischemia encephalopathy(HIE), so as to explore its mechanism underlying improvement of learning and memory. ICR mice (aged 7 days) were randomly divided into sham operation, model and moxibustion groups. HIE model was induced by ligation of the right common carotid artery combined with hypoxia in a closed transparent chamber. Mice in the moxibustion group were treated with gentle moxibustion at "Dazhui"(GV14) for 35 min，once daily for 3 consecutive days. The pathological changes of brain tissues were observed with the naked eyes and under microscope after H.E. staining, respectively. The expressions of pCaMKⅡα and NeuN in the ischemic penumbra were examined by immunofluorescent staining, and the learning and memory ablility was tested with Morris maze. No infarcts were found in the brain tissue of the mice in the sham operation group. Compared with the sham operation group, mice in the model group had infarcts and the expression of pCaMKⅡα and NeuN in the ischemic penumbra was significantly reduced (P<0.01), and the latency to find a platform was significantly prolonged in Morris maze test (P<0.01). After moxibustion, in comparison with the model group showed that, small areas of infarction were seen in the right hemisphere of the moxibustion group, and the expressions of pCaMKⅡα, NeuN increased significantly (P<0.01), and the latency to find a platform was significantly shortened (P<0.01). Moxibustion can improve the ability of learning and memory in the neonatal mice with HIE, which might be related to alleviating brain injury and increasing the expression of pCaMKⅡα in neurons of ischemic brain tissues.

Effect of intra-hippocampal lead injection on affective and cognitive disorders in male WISTAR rats: Possible involvement of oxidative stress

This paper is focused on affective and cognitive disorders induced by direct exposure to lead chloride (Pb) and the possible implication of oxidative stress in male WISTAR rats. Using stereotaxic surgery, a group of male wistar rats received an intracerebral injection of 3 μL of lead chloride (1 mg / L) into the right hippocampus or 3 μL of 0.9% Nacl for shame operated controls groups. After 4 days of rest, a series of benchmark neurobehavioral tests were made to evaluate affective and cognitive behaviors, such as open field test (OFT) and Elevated plus maze (EPM) for anxiety like behavior; Forced swim test (FST) for depressive like behavior; finally Y maze (Y-Maze) and Morris maze (MWM) tests for working memory, spatial learning and spatial memory. The data showed that Pb induces anxiogenic and depressogenic effects but does not induce a significant effect in memory. Then by measuring oxidative stress markers using the hippocampal assay of lead-treated rats, it’s appears that Pb can increase nitrogen monoxide, lipid peroxidation and reduces significantly the activity of superoxide dismutase. Therefore, our results showed that Pb is able to induce affective disorders and increase highly oxidative stress but has an insignificant effect on cognitive impairment.

Edaravone Administration Confers Neuroprotection after Experimental Intracerebral Hemorrhage in Rats via NLRP3 Suppression

ObjectivesIntracerebral hemorrhage (ICH) is one of the leading causes of disability and mortality in adult, which lacks effective therapies. Edaravone has showed its neuroprotective effects after ischemia stroke, but its effects and possible mechanisms after ICH are poorly understood. Here, we investigated whether edaravone confers neuroprotection after ICH in rats and explored the potential mechanisms involved. MethodsICH was induced in the right basal ganglia of Sprague-Dawley rats by stereotacticly injection of 200 μl autologous blood. Edaravone (3 mg/kg) or vehicle (saline) was administered intravenously and NLRP3 selective antagonist (MCC950, 10 mg/kg) was intraperitoneally injected to study the potential mechanism. Water Morris Maze Test and Rotarod test were used to elucidate neurological function and Fluoro-Jade C was used to study neurodegeneration after ICH. Western blot assay, Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and immunohistochemistry were used to check the expression of molecules involved. ResultsAs a result, we found that edaravone significantly alleviated brain edema and conferred the neurological deficits of rats after ICH. Hematoma increased NLRP3 expression in microglia, which was decreased by edaravone. Moreover, we demonstrated that edaravone shared a similar effect with MCC950 on alleviating neurodegeneration and decreasing the expression of IL-1β, Caspase 1 and NF-κB in protein or mRNA. Lastly, edaravone and MCC950 both increased the number of Tuj-1 positive neuronal cells peripheral hematoma. ConclusionsThe present study demonstrated that edaravone conducted neuroprotection after ICH partially via suppressing NF-κB-dependent NLRP3 in microglia, which contributed a novel evidence for clinic usage of edaravone after ICH.

Comparative Analyses of DHA‐Phosphatidylcholine Forage and Liposomes on Alzheimer's Disease in SAMP8 Mice

The present work comparatively evaluates the efficacy of docosahexaenoic acid – phosphatidylcholine (DHA‐PC) forage and liposome on Alzheimer's disease (AD) in the senescence‐accelerated prone 8 (SAMP8) mice and illustrates the potential mechanism. The dose of DHA‐PC in forage group (1% of total diets) is equal to that of liposome group. The results of Morris maze test show that both DHA‐PC forage and liposome obviously alleviated cognitive impairment (P &lt; 0.05). Moreover, the administration of DHA‐PC liposome shows advantage than forage in reducing β‐amyloid (Aβ) accumulation (P &lt; 0.05). Meanwhile, DHA‐PC forage exhibits excellent inhibition on the IL‐1β protein expression (P &lt; 0.05) and improvement in the protein levels of SYN and BDNF (P &lt; 0.05). These data are the first to perform comparative analysis of DHA‐PC forage and liposome on AD.Practical Applications: The outcomes in the present study might help to understand the bioactivities of DHA‐PC forage and liposomes, which might exert potential application value for dietary supplement with neuroprotective effects.Both docosahexaenoic acid – phosphatidylcholine (DHA‐PC) forage and liposome shows benefits in alleviating Alzheimer's disease development in senescence‐accelerated prone 8 mice by inhibiting β‐amyloid generation, oxidative stress, apoptosis, neural inflammation, and enhancing neurotrophins pathway in different degrees.

Exercise and probiotics attenuate the development of Alzheimer's disease in transgenic mice: Role of microbiome.

It has been suggested that exercise training and probiotic supplementation could decelerate the progress of functional and biochemical deterioration in APP/PS1 transgenic mice (APP/PS1TG). APP/PS1TG mice were subjected to exercise training and probiotic treatments and functional, biochemical and microbiome markers were analyzed. Under these conditions the mice significantly outperformed controls on The Morris Maze Test, and the number of beta-amyloid plaques decreased in the hippocampus. B. thetaiotaomicron levels correlated highly with the results of the Morris Maze Test (p < 0.05), and this group of bacteria was significantly elevated in the microbiome of the APP/PS1TG mice compared to the wild type. L. johnsonii levels positively correlated with the beta amyloid content and area. Data revealed that exercise and probiotic treatment can decrease the progress of Alzheimer's Disease and the beneficial effects could be partly mediated by alteration of the microbiome.

Protective effect and mechanism of quercetin on learning and memory function after global ischemia/reperfusion injury in rats

Objective To observe the effect of quercetin (Que) on neurological behavior, cell apoptosis and apoptosis-related protein expression in hippocampus after global cerebral ischemia/reperfusion (I/R) injury. Exploring the mechanism of quercetin-induced neuroprotective effect against global cerebral I/R injury. Methods Seventy two Male SD rats were randomly divided into 4 groups (n=18): sham+vehicle group (S group), I/R+vehicle group (I/R group), I/R+Que 5 mg·kg-1·d-1 group (Q5 group) and I/R+Que 10 mg·kg-1·d-1 group (Q10 group). The global cerebral ischemia reperfusion model was established by a four-vessel occlusion (4-VO) ligation method, and the duration of ischemia was 15 min. Sham-operated animals were treated similarly to those in the ischemic group, but neither the vertebral arteries nor the common carotid arteries were occluded. The rats in Q5 group and Q10 group were administered with 0.05%, 0.10% of the quercetin solution by garage at the dose of 5 mg·kg-1·d-1 and 10 mg·kg-1·d-1 respectively. S group and I/R group were given equal volume of vehicle. The quercetin and vehicle were administrated by gavage once per day 3 d before I/R and continued till the end of observation. The Morris maze test was performed 8 d after reperfusion. At 24 h after reperfusion, TUNEL staining and Annexin V-FITC/PI double labeled flow cytometry were used to evaluate apoptosis in hippocampus tissue, the expressions of Bcl-2, Bcl-xl, survivin, cleaved caspase-3, phosphorylated protein kinase B(p-Akt), Bad, p-Bad protein were determined by Western blot. Results In Morris water maze test, escape latency results showed that compared with I/R group, the escape latency in Q5 group and Q10 group was obviously reduced (P<0.05). Space probe test showed that the active time in the target quadrant in Q5 group and Q10 group were significantly longer than active time in the target quadrant (P<0.05). The frequency of crossing the original position platform was significantly increased (P<0.05). TUNEL assay showed that a large number of apoptotic cells in I/R group, while less positive cells could be seen in Q5 group and Q10 group. Annexin V-FITC/PI double staining flow cytometry detection results showed that the proportion of apoptotic cells in Q5 group and Q10 group were significantly reduced (P<0.05). Western blot results showed that Bcl-2, Bcl-xl, survivin, p-Akt and p-Bad expression levels were significantly increased in Q5 group and Q10 group (P<0.05) while cleaved caspase-3 expression level was significantly decreased (P<0.05). Conclusions Quercetin can up-regulate the expression of p-Akt, p-Bad, Bcl-2, Bcl-xl and survivin while down-regulate the expression of cleaved caspase-3, which leads to the inhibition of apoptosis, eventually protects neuron cells from global cerebral I/R injury and improves the learning and memory function. Key words: Quercetin; Cerebral ischemia-reperfusion; Learning; Memory; Hippocampus; Apoptosis

PO-233 The Neuroprotective Effects of Aerobic Exercise and Oral Resveratrol on Hippocampal Neurons in Diabetic Rats

Objective The purpose of this study is to explore the effects of aerobic exercise combined with oral resveratrol on ethology and BDNF and CREB proteins of hippocampus neurons in diabetic rats, in order to provide a theoretical basis for revealing the neuroprotective mechanism of exercise and resveratrol.&#x0D; Methods 45 male Sprague Dawley rats, aged 8 weeks, were randomly divided into 5 groups: normal control (NC), diabetes control (DC), diabetes exercise (DE), diabetes resveratrol (DR) and diabetes exercise and resveratrol (DER). Exercise-related groups performed 8-week swimming training (60min/d，5d/week). Morris maze test, 7d. Escape latency time, strategy of finding platform performance, the protein expression of BDNF and CREB from hippocampus neurons were measured.&#x0D; Results 1）Compared with DM, DR and RE groups, the escape latency of DRE group was significantly shortened (p&lt;0.01), and the strategy of finding platform performance was remarkably improved (p&lt;0.05). 2) Compared with NC group, the protein expression of BDNF of DM group was obviously decreased (p &lt;0.01), while in DRE group was improved significantly than that in DE group (p&lt; 0.05). 3) The level of CREB expression in DM group clearly lower than in group NC (p&lt;0.01), and the expression of CREB in DER and DE groups were remarkably increased (P &lt;0.01) .&#x0D; Conclusions Eight weeks of swimming training and/or oral resveratrol could increase the expression level of BDNF and CREB protein in the hippocampal neurons of diabetic rats, and improve the ability of spatial learning from behavioral study. It is suggested that the aerobic exercise training and the SIRT1 mechanism of resveratrol perhaps improve the situation of high glucose and indirectly stimulate the expression of BDNF and CREB protein. As a result, that leads to improve the impair of learning and memory which caused by diabetes.&#x0D;

Radix Scutellariae Attenuates CUMS-Induced Depressive-Like Behavior by Promoting Neurogenesis via cAMP/PKA Pathway.

Chronic mild unpredictable stress (CUMS) causes neurogenesis damage in the hippocampus and depressive-like behaviors such as cognitive impairment. Radix Scutellariae from the dry root of Scutellaria baicalensis Georgi, with the common name Baikal skullcap. In this study, we demonstrated that Radix Scutellariae (RS 500, 1000mg/kg) notably improved the behavior of the rat, such as shortened escape latency in morris maze test, reduced immobility time in tail suspension test and in forced swimming test, as well as increased sucrose consumption in sucrose preference test. In addition, RS alleviated the damage CUMS-induced neurogenesis and the reduced levels of BrdU; DCX and NeuN, the neurons hallmark of hippocampus neurogenesis. Moreover, associated proteins in cAMP/PKA pathway were up-regulated after RS treatment. By HPLC analysis, we found that RS decoction contains four main components, including baicalin, baicalein, wogonoside and wogonin, respectively. In conclusion, RS could exert a natural antidepressant with improving depressive-like behavior via regulation of cAMP/PKA neurogenesis pathway.

Mechanisms of DHA-enriched phospholipids in improving cognitive deficits in aged SAMP8 mice with high-fat diet

Recent studies have shown that a high-fat diet (HFD) is involved in both metabolic dysfunction and cognitive deficiency and that docosahexaenoic-acid-enriched phospholipids (DHA-PLs) have beneficial effects on obesity and cognitive impairment. However, there are only a few studies comparing differences between DHA-PC and DHA-PS in HFD-induced Alzheimer's disease (AD) models. After 8 weeks feeding with HFD, 10-month-old SAMP8 mice were fed with 1% (w/w) DHA-PC or 1% DHA-PS (biosynthesized from DHA-PC) for 8 weeks; we then tested the behavioral performances in the Barnes maze test and Morris maze test. The changes of the generation and accumulation of Aβ, oxidative stress, apoptosis, neuroinflammation and neurotrophic factors were also measured. The results indicated that both DHA-PC and DHA-PS significantly improved the metabolic disorders and cognitive deficits. Both DHA-PC and DHA-PS could ameliorate oxidative stress, and DHA-PS presented more notable benefits than DHA-PC on Aβ pathology, mitochondrial damage, neuroinflammation and neurotrophic factors; DHA-PS was for the first time found to increase the production of insoluble Aβ (less pathogenic) in this AD model. These data suggest that DHA-PLs can significantly improve cognitive deficiency, and the molecular mechanisms for this closely relate to the phospholipid polar groups.

EPA enriched ethanolamine plasmalogens significantly improve cognition of Alzheimer’s disease mouse model by suppressing β-amyloid generation

EPA enriched ethanolamine plasmalogens (EPA-pPE) are important bioactive components and widely distributed in multifarious marine products. In the present study, Chinese hamster ovary cells stably transfected with APP751 and PS1 (CHO-APP/PS1 cells) and high-fat feeding SAMP8 mice were used to study the effects of EPA-pPE on Alzheimer’s disease (AD). The in vitro experiments showed that EPA-pPE exerted better effects than EPA-PE and Egg-PE in decreasing the intracellular and extracellular Aβ levels. EPA-pPE obviously improved learning and memory function of high-fat feeding SAMP8 mice by Morris maze test. Further mechanism research indicated that EPA-pPE could significantly improve cognition of Alzheimer’s disease by suppressing β-amyloid generation via reducing levels of APP and altering APP cleavage, thereby inhibiting oxidative stress, hyper-phosphorylated tau, neuro-inflammation and apoptosis. These results suggested that EPA-pPE might be applied as food supplements and/or functional ingredients to relieve neurodegenerative disease.