Mechanism of Learning and Memory Impairment in Rats Exposed to Arsenic and/or Fluoride Based on Microbiome and Metabolome / 生物医学与环境科学（英文）

OBJECTIVE@#Arsenic (As) and fluoride (F) are two of the most common elements contaminating groundwater resources. A growing number of studies have found that As and F can cause neurotoxicity in infants and children, leading to cognitive, learning, and memory impairments. However, early biomarkers of learning and memory impairment induced by As and/or F remain unclear. In the present study, the mechanisms by which As and/or F cause learning memory impairment are explored at the multi-omics level (microbiome and metabolome).@*METHODS@#We stablished an SD rats model exposed to arsenic and/or fluoride from intrauterine to adult period.@*RESULTS@#Arsenic and/fluoride exposed groups showed reduced neurobehavioral performance and lesions in the hippocampal CA1 region. 16S rRNA gene sequencing revealed that As and/or F exposure significantly altered the composition and diversity of the gut microbiome，featuring the Lachnospiraceae_NK4A136_group, Ruminococcus_1, Prevotellaceae_NK3B31_group, [Eubacterium]_xylanophilum_group. Metabolome analysis showed that As and/or F-induced learning and memory impairment may be related to tryptophan, lipoic acid, glutamate, gamma-aminobutyric acidergic (GABAergic) synapse, and arachidonic acid (AA) metabolism. The gut microbiota, metabolites, and learning memory indicators were significantly correlated.@*CONCLUSION@#Learning memory impairment triggered by As and/or F exposure may be mediated by different gut microbes and their associated metabolites.

TRPV4-induced Neurofilament Injury Contributes to Memory Impairment after High Intensity and Low Frequency Noise Exposures / 生物医学与环境科学（英文）

OBJECTIVE@#Exposure to high intensity, low frequency noise (HI-LFN) causes vibroacoustic disease (VAD), with memory deficit as a primary non-auditory symptomatic effect of VAD. However, the underlying mechanism of the memory deficit is unknown. This study aimed to characterize potential mechanisms involving morphological changes of neurons and nerve fibers in the hippocampus, after exposure to HI-LFN.@*METHODS@#Adult wild-type and transient receptor potential vanilloid subtype 4 knockout (TRPV4-/-) mice were used for construction of the HI-LFN injury model. The new object recognition task and the Morris water maze test were used to measure the memory of these animals. Hemoxylin and eosin and immunofluorescence staining were used to examine morphological changes of the hippocampus after exposure to HI-LFN.@*RESULTS@#The expression of TRPV4 was significantly upregulated in the hippocampus after HI-LFN exposure. Furthermore, memory deficits correlated with lower densities of neurons and neurofilament-positive nerve fibers in the cornu ammonis 1 (CA1) and dentate gyrus (DG) hippocampal areas in wild-type mice. However, TRPV4-/- mice showed better performance in memory tests and more integrated neurofilament-positive nerve fibers in the CA1 and DG areas after HI-LFN exposure.@*CONCLUSION@#TRPV4 up-regulation induced neurofilament positive nerve fiber injury in the hippocampus, which was a possible mechanism for memory impairment and cognitive decline resulting from HI-LFN exposure. Together, these results identified a promising therapeutic target for treating cognitive dysfunction in VAD patients.

Research progress on the modulation mechanism of electroacupuncture for learning and memory impairment after ischemic stroke / 中国针灸

Electroacupuncture may play a role in treatment of learning and memory impairment after ischemic stroke by regulating phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA)/cAMP response element binding protein (CREB) signaling pathway, nerve growth factor (NGF)/tyrosine kinase-A (TrkA) signaling pathway, Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway, Notch signaling pathway, erythropoietin-producing hepatocyte (Eph)/ephrin signaling pathway. The interactions among these pathways should be further explored in treatment of learning and memory impairment after ischemic stroke.

Effect of Tongdu Xingshen Needling Method （通督醒神针刺法） on Expression of AMPA Receptors and Their Accessory Proteins in the Hippocampus of Rats with Learning Memory Impairment After Cerebral Ischaemia-Reperfusion / 中医杂志

ObjectiveTo explore the possible mechanism of Tongdu Xingshen needling method （通督醒神针刺法） on post-stroke cognitive impairment. MethodsSD rats were randomly divided into a normal group （n=12）， a sham surgery group （n=12）， a model group （n=12）， and a electroacupuncture group （n=13）. The rats in the model group and electroacupuncture group were subjected to the wire bolus method to establish the rats model with learning memory impairment after cerebral ischaemia-reperfusion. After successful modelling， the rats in the electroacupuncture group were given electroacupuncture interventions at “Shenting （GV 24）” and “Baihui （GV 20）” once a day for 30 minutes for 14 days. The other three groups did not receive other interventions but grasp. A 5-day localisation navigation experiment was conducted on the 9th day of intervention， and a spatial exploration experiment was conducted on the 14th day of intervention to evaluate the learning and memory abilities of the rats. After the spatial exploration experiment， hippocampal tissues were taken from each group of rats， and the changes in the volume of cerebral infarction were observed by TTC staining； the changes in the morphology of pyramidal neurons and the density of dendritic spines in the CA1 area of the hippocampus were observed by Golgi staining； protein immunoblotting was used to detect the relative protein expression of the subunits of the α-amino-3-carboxy-5-methylisoxazole-4-propionic acid （AMPA） receptor including glutamate receptor 1 （GluR1）， glutamate receptor 2 （GluR2）， glutamate receptor 3 （GluR3） and auxiliary proteins TARPγ2， TARPγ8 in hippocampal tissues of rats in each group； the real-time fluorescence quantitative PCR was used to detect GluR1， GluR2， GluR3 mRNA levels in the hippocampal tissues of rats. ResultsIn the localisation navigation experiment， compared with the normal group and sham surgery group， the escape latency and total distance of rats in the model group were significantly extended （P＜0.05） at day 1， 2， 3， 4， and 5； and the escape latency and total distance of rats in the electroacupuncture group tended to be significantly shorter than those in the model group （P＜0.05）. In the spatial exploration experiment， compared with the normal group and the sham surgery group， the number of rats crossing the platform in the model group was significantly reduced （P＜0.05）， and the number of crossings of the platform in the electroacupuncture group increased significantly （P＜0.05）. The results of TTC staining showed that the volume of cerebral infarction increased clearly in the model group compared with the sham surgery group （P＜0.05）， and apparently decreased in the electroacupuncture group compared with the model group （P＜0.05）. Golgi staining showed that the number of dendritic branches of pyramidal neurons and dendritic spines in hippocampal CA1 region significantly decreased in the model group compared with the normal group and the sham surgery group （P＜0.05）. The number of dendritic branches of pyramidal neurons and the density of dendritic spines in hippocampal CA1 region significantly increased in the electroacupuncture group compared with the model group （P＜0.05）. The protein relative expression levels of GluR1， GluR2， GluR3， TARPγ2 and TARPγ8， and the mRNA levels of GluR1， GluR2 and GluR3 in hippocampus decreased in the model group compared with the normal group and the sham surgery group （P＜0.05）. The protein relative expression levels of GluR1， GluR2， GluR3， TARPγ2 and TARPγ8， and the mRNA levels of GluR1， GluR2 and GluR3 in hippocampus increased in the electroacupuncture group compared with model group （P＜0.05）. ConclusionThe Tongdu Xingshen needling method can improve learning memory impairment after cerebral ischaemia-reperfusion， which may be related to up-regulation of the expression of AMPA receptor and their auxiliary protein TARP， and promoting the synaptic plasticity of hippocampal tissues.

Is the use of high-intensity atorvastatin associated with memory impairment?

High-intensity statins are the cornerstone of medical management in Acute Coronary Syndromes (ACS). However, their effect on neurocognition are less clear. In this prospective observational study, we gave guideline-directed high-intensity atorvastatin 40 mg to middle-aged statin-naïve ACS patients. Memory assessments were performed before and 6 months after statin therapy using 2 validated scales-the PostGraduate Institute Memory Scale (PGI-MS), and the Logical Memory Passage Test (LMPT). There was no significant difference in the mean PGI-MS test scores (baseline 75.4 ± 7.9, 6months 76.5 ± 8.2;p ¼ 0.26) or the overall composite scores (baseline 32.02 ± 3.2, 6months 32.8 ± 3.1; p ¼ 0.20), after 6 months of statin use. There was a small improvement in immediate recall (baseline score 8.5 ± 2.5, 6 months 9.04 ± 1.8; p ¼ 0.05), and delayed recall (baseline 6.1 ± 2.6, 6 months 6.9 ± 1.9, p ¼ 0.002). High-intensity atorvastatin use did not affect memory at 6 months among statin-naïve middle-aged patients with ACS.

Effect of histone deacetylase inhibitor on neuropathic pain and pain-induced memory impairment in mice / 中华行为医学与脑科学杂志

Objective:To investigate the effect and mechanism of non-selective histone deacetylase (HDAC) inhibitor sodium butyrate (NaB) on neuropathic pain and pain-induced memory impairment in mice.Methods:Forty clean grade male C57BL/6J mice were were divided into 4 groups by random number table method ( n=10 in each group): sham + saline, sham + NaB, chronic constriction injury (CCI)+ saline and CCI + NaB.The mouse CCI model was established by sciatic nerve ligation. Non-selective HDAC inhibitors NaB(300 mg/kg) was intraperitoneally injected into the mice in Sham+ NaB group and CCI+ NaB group once a day 15-28 days after modeling, while the mice in Sham+ saline group and CCI+ saline group were intraperitoneally injected with the same volume of saline. On the 14th and 28th day after operation, the athletic ability was measured by open field test (OFT), the pain behavior was measured by paw withdrawal threshold (PWT) and paw withdrawal latency (PWL), and the memory function was measured by Y-maze. After the behavioral experiment, hippocampus and spinal dorsal horn tissues were taken for the activity of HDAC measurement, and hippocampus tissues were taken for the expression levels of BDNF and PSD95 measurement. SPSS 25.0 software was used for statistical analysis. The data were compared by repeated measurement ANOVA and one-way ANOVA. Results:After treatment with NaB, the interaction effects of the accuracy of spontaneous alternation of PWT, PWL and Y maze in mice were significant( F=21.07, 6.98, 7.79, all P<0.05). Compared with the Sham + saline group, the PWT((0.83±0.30)g, (0.25±0.22)g, (0.24±0.11)g; both P<0.05), the PWL((14.97±4.02)s, (5.99±1.51)s, (6.87±0.90)s; both P<0.05) and the spontaneous alternation in Y maze(71.57±2.80)%, (56.96±0.60)%, (62.86±4.94)%; both P<0.05) in CCI+ Saline group and CCI+ NaB group were lower. After treatment with NaB, compared with CCI + saline group, PWT((0.22±0.13)g, (0.62±0.23)g; P<0.05), PWL((5.62±2.00)s, (8.82±2.13)s; P<0.05)and the accuracy of spontaneous alternation of Y maze were significantly higher ((56.54±7.50)%, (66.35±8.20)%; P<0.05), the HDAC activity in hippocampus((173.40±7.38)%, (122.70±8.40)%; P<0.05)and in spinal cord ((153.40±10.58)%, (111.40±11.40)%; P<0.05)were significantly lower, and the expression of BDNF((0.65±0.06), (0.87±0.43); P<0.05)and PSD95((0.70±0.40), (0.87±0.04); P<0.05)were significantly higher in CCI + NaB group. Conclusion:NaB can improve neuropathic pain and pain-induced memory impairment.The mechanism may be related to the inhibition of HDAC activity and the up-regulation of BDNF and PSD95 expression in hippocampus.

Effects and mechanism of the ethanol extract of Tiarella polyphylla on learning and memory impairment in mice / 中国药房

OBJECTIV E To investigate the effect s and mechanism of the ethanol extract of Tiarella polyphylla （“TPE”）on learning and memory impairment in mice. METHODS Male Kunming mice were randomly divided into normal group ，model group，positive group （donepezil hydrochloride 4 mg/kg）and TPE low-dose ，medium-dose and high-dose groups （150，300，600 mg/kg），with 10 mice in each group. Drug administration groups were given relevant medicine intragastrically once a day ，and normal group and model group were given water intragastrically once a day ，for consecutive 22 d. On the 17th day ，administration groups and model group were intraperitoneally injected with scopolamine hydrobromide （3 mg/kg）to establish a model of learning and memory impairment. The learning and memory ability of the mice were evaluated by the Morris water maze. Hematoxylin-eosin （HE） staining was used for morphological observation of hippocampus cells of the mice. The levels of acetylcholinesterase （AChE），choline acetyltransferase （ChAT），superoxide dismutase （SOD），malondialdehyde（MDA），interleukin-6（IL-6）and tumor necrosis factor-α（TNF-α）in cerebral tissue as well as the relative expression of phosphorylated Tau protein （p-Tau），β-site amyloid precursor protein cleaving enzyme 1（BACE1）and amyloid precursor protein （APP）in hippocampus tissue were all detected. RESULTS The escape latency of mice in positive group ，TPE medium-dose and high-dose groups were all significantly shortened than the model group on the 4th to 5th day of training ，while the times of crossing platform and the percentage of movement distance in target quadrant were significantly increased （P＜0.05）. Compared with model group ，the neurons in the hippocampal CA 1 region of mice were increased to var ying degrees in administration groups ，the ne urons in solidified and atrophic state decreased ，and the arrangement of neurons tended to be close；the levels of ChAT and SOD in cerebral tissue were significantly increased in positive group and TPE medium-dose and high-dose groups ；the levels of AChE ，MDA，IL-6，the levels of TNF-α and relative expression of p-Tau ，BACE1 and APP in hippocampus tissue were decreased significantly （P＜ 0.05）. CONCLUSIONS TPE can improve the learning and memory impairment induced by scopolamine in mice ，and the mechanism may be related to balancing the brain cholinergic system ，alleviating oxidative stress injury ，improving inflammatory response，and inhibiting the overexpression of p-Tau ，BACE1 and APP .

Effect of traditional Chinese medicine Syngnathus on D-galactose-induced learning and memory impairment in aging mice / 药学实践杂志

Objective To study the effect of traditional Chinese medicine, Syngnathus on learning and memory impairment induced by D-galactose in aging mice and its mechanism of action. Methods HPLC was used to determine the content of DHA, the active ingredient in anti-learning and memory impairment in Syngnathus. The aging mouse model was prepared by intraperitoneal injection of D-galactose (D-gal). Morris water maze test and Western blot were used to detect the ability of learning and memory, biochemical indicators and protein expression related to oxidative damage in the hippocampus, and to explore the protective effect and mechanism of Syngnathus on learning and memory impairment in aging mice. Results HPLC results showed that the DHA content in Syngnathus was 7.761 3 mg/g (calculated as crude drug), accounting for about 47% of the total composition. Morris water maze results showed that Syngnathus could reduce the escape latency of learning and memory-impaired aging mice and increase the target quadrant swimming time, the proportion of swimming distance and the number of times of crossing the platform, and improve the learning and memory impairment of mice. In addition, Syngnathus can activate the AKT/FOXO1/SOD2 signaling pathway in the hippocampus of aging mice with learning and memory impairment, promote the expression of oxidative stress pathway-related proteins, and improve the learning and memory impairment in aging mice by reducing the degree of oxidative damage in the hippocampus of aging mice. Conclusion This study found that Syngnathus is rich in DHA, which has the effect of improving learning and memory impairment induced by D-galactose in aging mice, and preliminarily clarified that its mechanism of action is related to anti-oxidation. Experimental evidence is provided.

The psycho nourishing effect of dance and musical training : a population based evaluation

Introduction: In the twenty first century, mental health hazards are growing by lips and bounce. Worldwide reports based on several empirical data poses a serious threat for near future. Memory skill and emotional management are central to many neurocognitive and neuro psychiatric illness. Music and dance, the ancients of performing arts, have long been identified as mind relaxant and mind-body coordinator. Efforts are regularly made to include these performing art forms in non-invasive therapeutics. Most of the data are based on clinical patients and few on healthy subjects. But whether learning these art forms for a long time give any benefit in daily life is still not very apparent from experimental data. Thus, the present study aimed to investigate the impact of long-term training in this field on working memory impairment (WMI) and emotional regulation (ER). Methodology: Individuals were recruited based on their soulful agreement to participate in the study. WMI and ER were assessed using validated questionnaires for each participant. Anonymized data obtained from participants were further analysed using suitable statistical methods. Results: Finding from analysed outputs suggested a beneficial impact of long-term training in music and dance; WMI was significantly lower in the trained individuals (P<0.05). Significant difference in ER (P<0.05) was also evident, especially among the young aspirants. Conclusion: Long term training in music and dance can be a potentially preventive as well as therapeutic intervention from stress, dementia, and other sort of mental illness.

Targeting redox-altered plasticity to reactivate synaptic function: A novel therapeutic strategy for cognitive disorder

Redox-altered plasticity refers to redox-dependent reversible changes in synaptic plasticity

Probiotics modulate the microbiota-gut-brain axis and improve memory deficits in aged SAMP8 mice

ProBiotic-4 is a probiotic preparation composed of , , , and . This study aims to investigate the effects of ProBiotic-4 on the microbiota-gut-brain axis and cognitive deficits, and to explore the underlying molecular mechanism using senescence-accelerated mouse prone 8 (SAMP8) mice. ProBiotic-4 was orally administered to 9-month-old SAMP8 mice for 12 weeks. We observed that ProBiotic-4 significantly improved the memory deficits, cerebral neuronal and synaptic injuries, glial activation, and microbiota composition in the feces and brains of aged SAMP8 mice. ProBiotic-4 substantially attenuated aging-related disruption of the intestinal barrier and blood-brain barrier, decreased interleukin-6 and tumor necrosis factor- at both mRNA and protein levels, reduced plasma and cerebral lipopolysaccharide (LPS) concentration, toll-like receptor 4 (TLR4) expression, and nuclear factor-B (NF-B) nuclear translocation in the brain. In addition, not only did ProBiotic-4 significantly decreased the levels of -H2AX, 8-hydroxydesoxyguanosine, and retinoic-acid-inducible gene-I (RIG-I), it also abrogated RIG-I multimerization in the brain. These findings suggest that targeting gut microbiota with probiotics may have a therapeutic potential for the deficits of the microbiota-gut-brain axis and cognitive function in aging, and that its mechanism is associated with inhibition of both TLR4-and RIG-I-mediated NF-B signaling pathway and inflammatory responses.

Overexpression of Purinergic P2X4 Receptors in Hippocampus Rescues Memory Impairment in Rats with Type 2 Diabetes / 神经科学通报·英文版

Purinergic receptors have been reported to be involved in brain disorders. In this study, we explored their roles and mechanisms underlying the memory impairment in rats with type 2 diabetes mellitus (T2DM). T2DM rats exhibited a worse performance in the T-maze and Morris water maze (MWM) than controls. Microglia positive for P2X purinoceptor 4 (P2X4R) in the hippocampus were reduced and activated microglia were increased in T2DM rats. Long Amplicon PCR (LA-PCR) showed that DNA amplification of the p2x4r gene in the hippocampus was lower in T2DM rats. Minocycline significantly reduced the number of activated microglia and the mean distance traveled by T2DM rats in the MWM. Most importantly, P2X4R overexpression suppressed the activated microglia and rescued the memory impairment of T2DM rats. Overall, T2DM led to excessive activation of microglia in the hippocampus, partly through the DNA damage-mediated downregulation of P2X4Rs, thus contributing to memory impairment.

Effect of Ultrafine Powder of Gastrodiae Rhizoma in Improving Learning and Memory Ability of Vascular Dementia Rats by Regulating Cholinergic System / 中国实验方剂学杂志

Objective:To investigate whether ultrafine powder of Gastrodiae Rhizoma （UPG） can alleviate the learning and memory impairment of vascular dementia rats and delay the process of VD， and whether this effect is related to the release of acetylcholine （Ach） through the regulation with acetylcholinesterase （AChE） and choline acetyltransferase （ChAT） and control of cholinergic system. Method:SD rats were randomly divided into sham operation group， UPG low dose group （0.45 g·kg-1）， UPG high dose group （1.8 g·kg-1） and Huperzine A group （80 μg·kg-1）， with 12 rats in each group. The drug administration groups were given orally drugs once a day for 8 weeks， and sham group and model group were given orally the same amount of distilled water. The learning and memory ability of the rats with VD were evaluated by the Morris water maze. Htoxylin eosin（HE） staining was used for pathomorphological observation of hippocampus CA1 area of the rats. The content of Ach was determined by enzyme-linked immunosorbent assay（ELISA）， AChE and ChAT protein expressions were detected by Western blot， and expression of ChAT in hippocampus CA1 area was observed by immunohistochemistry. Result:Compared with the sham operation group， the escape latency of the model group was significantly increased （P<0.01）， and the frequency of crossings platform and the time of staying in the target quadrant were reduced significantly （P<0.01）. HE staining of hippocampal tissues from VD rat showed neuron disorders， loss and degeneration and necrosis， pyknosis of the nucleus and light coloration of the cytoplasm. The level of acetylcholine in the hippocampus was significantly decreased by ELISA （P<0.05）， the expression level of AChE protein was significantly up-regulated， and the expression level of ChAT protein was significantly down-regulated （P<0.01）. Compared with model group， each administration group could significantly reduce the escape latency of the model rats， and significantly increase the frequency of crossing platform and the time of staying in the target quadrant （P<0.01）， the content of Ach was significantly increased （P<0.05）， the expression of AChE protein was significantly down-regulated （P<0.01）， while the expression of ChAT protein was significantly up-regulated （P<0.01）. Conclusion:UPG improves the learning and memory ability of vascular dementia rats， and its mechanism may be related to the increase of Ach， ChAT level and the decrease of AChE level.

Effective use of vitamin D in mild cognitive impairment in older people

Introduction. With age, there is a growing risk of vitamin D deficiency and cognitive impairment. Maintaining the older people's health is socially relevant to health systems in the light of the population ageing trend. The study was aimed at identifying the relationship of vitamin D levels and symptoms of moderate cognitive impairment in older people. Methods. The authors conducted a cross-sectional screening of vitamin D status and cognitive impairment using the memory impairment screen (MIS) questionnaire, as well as the clinical, placebo-controlled study of vitamin D intake at a dose of 2,000 IU/day for 6 months. Results. The frequency of vitamin D deficiency in older patients with signs of cognitive impairment totaled 90.91 %, which was significantly more frequently compared with the group without cognitive impairment, where vitamin D deficiency was found only in 11.36 % of cases. In the dynamics on the background of the vitamin D intake for 6 months, the concentration in the intervention group amounted to 52.34 ± 2.43 ng/ml vs 14.71 ± 1.54 ng/ ml in the placebo group. The results of the study of cognitive impairment using MIS for the treatment group were 3.63 ± 0.01 points, which was significantly higher compared with the placebo group ­ 1.78 ± 0.22 points. A correlation analysis of vitamin D levels and MIS points showed a strong positive relationship, with a correlation coefficient of 0.92. Conclusion. The study identified a positive relationship of increasing vitamin D levels and reducing the symptoms of mild cognitive impairment in older people. Achieving vitamin D levels of over 40 ng/ ml greatly reduces the symptoms of cognitive impairment identified by the MIS questionnaire, however, the issue of treatment of impaired cognitive functions with vitamin D remains debatable.

Ameliorate effect and mechanism of verbascoside on memory impairment in hypoxic mice / 药学实践杂志

Objective To investigate the effects and mechanism of verbascoside on hypoxia-induced memory impairment.Methods The eight-arm maze was used to train mice′s spatial memory ability.After successful training, mice were randomly divided into five groups:a normoxic control group (distilled water, 0.1ml/10g), hypoxic model group (distilled water, 0.1ml/10g), the verbascoside low dose group (50 mg/kg), medium dose group (150 mg/kg), and high dose group (300mg/kg) were administered orally once a day for a total of 7days.After administration on the fourth day, except for the normoxic control group was placed in the animal room (1 500m), the remaining four groups were placed in a large-scale hypobaric chamber to simulate the hypoxic environment of the plateau (7 500m, 3days).Eight-armed maze test (4 000m) was used and the plasma and brain tissues were dissected out and measured for reactive oxygen species (ROS) in the brain, malondialdehyde (MDA), reduced glutathione (GSH) and total superoxide dismutase (T-SOD) activity in plasma and brain.Results Compared with the normoxic control group, the indexes of the eight-armed maze, ROS and MDA in the brain, MDA in the plasma of the hypoxia model group were significantly increased, and the GSH and T-SOD enzyme activities in the brain and plasma were notably decreased.Compared with the hypoxic model group, the indexes of the eight-armed maze, ROS and MDA in the brain, MDA in the plasma in the various groups of verbascoside were reduced more or less, the GSH and T-SOD enzyme activities in the brain and plasma slightly were increased.Conclusion Verbascoside could ameliorate the hypoxic memory impairment at high altitude, which might be related to the stabilization of the body′s antioxidant enzyme system balance and

Study on the Improvement Effects of Lanqian Buccal Tablet on Scopolamine-induced Learning and Memory Impairment of Mice / 中国药房

OBJECTIVE： To study the improvement effects of Lanqian buccal tablets on scopolamine-induced learning and memory impairment of mice. METHODS： The mice were randomly divided into blank group （normal saline）， model group （normal saline）， positive group （Donepezil hydrochloride tablets， 1.52 mg/kg） and Lanqian buccal tablets high-dose， medium-dose and low-dose groups （800， 400， 200 mg/kg）， with 14 mice in each group. Once a day， 30 days after continuous intragastric administration， except for blank group， other groups were intraperitioneal injected scopolamine hydrobromide 3 mg/kg to induce learning and memory impairment model. After modeling， the learning and memory ability of mice were evaluated with step through test （latency， mistake times of entering darkroom as indexes） and Morris water maze （the time of going up on the platform， the times of crossing the platform， swimming time in target quadrant as indexes）. The levels of Ach， ChAT， AchE， SOD and MDA in cerebral tissue of mice were determined. RESULTS： Compared with blank group， latency， the times of crossing the platform， swimming time in target quadrant， the levels of ChAT， Ach and SOD were shortened or decreased significantly in model group （P＜0.05 or P＜0.01）， while mistake times of entering darkroom， the time of going up on the platform， the levels of AchE and MDA were extended or rised significantly （P＜0.01）. Compared with model group， latency （except for Lanqian buccal tablet low-dose group）， the times of crossing the platform， swimming time in target quadrant， the levels of ChAT， Ach and SOD were extended or rised significantly in positive group and Lanqian buccal tablet groups （P＜0.05 or P＜0.01）. The mistake times of entering darkroom （except for Lanqian buccal tablet low-dose group）， the time of going up on the platform （except for Lanqian buccal tablet low-dose group） and the levels of AchE and MDA （except for Lanqian buccal tablet medium-dose and low-dose group） were shortened or decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS： Lanqian buccal tablet can improve scopolamine-induced learning and memory impairment of mice by increasing the levels of ChAT， Ach and SOD and decreasing the levels of AchE and MDA.

Effects of Dipyridamole on Learning and Memory Impairment in Rat with Vascular Dementia / 中国药学杂志

OBJECTIVE: To investigate the protective effects of dipyridamole on learning and memory impairment of vascular dementia (VD) in rats and explore the potential mechanisms. METHODS: 4-Vessel occlusion (4-VO) was performed to establish the model of VD. Spatial memory performance was examined using the Morris water maze and step-through passive avoidance tests. The mRNA and protein levels of nuclear factor (NF)-κB, tumor necrosis factor (TNF-α) and interleukin (IL) -1β were measured by RTPCR and Western-blot in the CA1 district of hippocampus, respectively. RESULTS: Compared with vehicle-treated controls, rats treated with 4-VO spented a longer time finding the hidden platform during the acquisition trials of the Morris water maze task; this was reversed by repeated treatment with dipyridamole. In the passive avoidance test, the model rats showed decreased retention tested 24 h after initial training; this was reversed by dipyridamole. The expression of NF-κB, TNF-α and IL-1β levels were increased after 4-VO performed and the dipyridamole significantly reduced the release of these inflammation-related factors. CONCLUSION: Dipyridamole could reverse the learning and memory impairment of VD by reducing the inflammation reaction.

Nacre extract prevents scopolamine-induced memory deficits in rodents

Objective:To investigate whether the extract from the nacreous layer of pearl oysters (nacre extract) improves impairments in memory caused by scopolamine administration in rodents.Methods:Nacre extract was prepared from the inner shell layer of pearl oyster. Effects of nacre extract on scopolamine-induced memory impairment were estimated using novel object recognition test, Y-maze test, and Barnes maze test. Effect of nacre extract on mRNA expressions which are genes associated with memory in the hippocampus was investigated using semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) analysis.Results:Administration of nacre extract led to the protection against scopolamine-induced impairments in object recognition, short-term memory, and spatial memory. Treatment with nacre extract reversed the mRNA expression of brain-derived neurotrophic factor (BDNF) and Homer protein homolog 1 (Homer-la) in the hippocampus, which decreased with the treatment of scopolamine.Conclusions:These results suggest that nacre extract has attenuating effects on memory impairments induced by scopolamine through the increase in mRNA expression of BDNF and Homer-1a.

Calcium carbonate supplementation causes memory impairment in mice

Objective:To investigate the influence of calcium carbonate supplementation on cognitive function in mice.Methods:Mice were fed diets containing 1.0% calcium carbonate for 8 weeks, following which they were evaluated for memory function using object recognition, Y-maze, and Barnes maze tests. Next, the expression levels of cAMP response element binding protein (CREB) and phosphorylated CREB, which is involved in the memory process were investigated in both the hippocampus and cerebral cortex using western blotting methods.Results:Mice fed on a diet containing calcium carbonate showed memory impairments in object recognition, Y-maze, and Barnes maze tests with respect to the mice that were on a control diet. Further, mice that were fed a diet containing calcium carbonate and a nimodipine (an L-type calcium channel antagonist), reversed calcium carbonate-induced memory impairments, thus suggesting that excessive entry of calcium in cells may cause memory impairments. A study using western blot revealed that expression of CREB and phosphorylated CREB in hippocampus and cerebral cortex was significantly lower in the calcium carbonate-fed mice than in the control-diet-fed mice.Conclusions:These results suggest that a calcium carbonate diet may cause memory impairment by decreasing CREB expression. This is the first report of calcium carbonate supplementation causing memory impairment. This simple animal model may be useful as a novel cognitive impairment model for drug development.

Correlation of memory impairment and cerebral perfusion in patients with vertebral-basilar artery stenosis / 中华行为医学与脑科学杂志

Objective To evaluate the correlation between cerebral blood flow perfusion and memory impairment in patients with severe stenosis of vertebral basilar artery (VBA).Methods 62 cases of patients with VBA stenosis diagnosed by digital subtraction angiography(DSA) in Beijing Tiantan Hospital from September 2016 to March 2017 were enrolled.Mental State Examination (MMSE),Clinical Memory Scale (CMS) test and CT perfusion(CTP) was performed.All patients were divided into memory normal group(n=24,including 1 excellent case,6 above normal cases,and 14 normal cases) and memory impairment group(n =38,including 18 below normal cases,12 periphery cases,8 impaired cases) according to CMS.The ratios of side-to-side period were compared between bilateral mesial temporal lobe and anterior circulation area.The relative time to peak (rTTP),relative mean transit time(rMTY),relative cerebral blood flow(rCBF) and relative cerebral blood volume (rCBV) were calculate.Results The incidence of CTP decompensation in the medial temporal lobe was higher than that in the patients with memory impairment(P＜0.05).The difference of rTTP and rMTT value between the two groups in the bilateral medial temporal lobes was statistically significant (rTFP:(1.131 ±0.037),(1.437±0.139),t=10.520,P＜ 0.05);rMTT:(1.081 ±0.059),(1.281 ±0.174),t=5.423,P＜0.05).Conclusion The patients with VBA severe stenosis are more likely to get memory impairment due to cerebral hypoperfusion.