Acteoside Attenuates Recognition Memory Impairment in CUMS Rats via Regulating Synaptic Plasticity and mTOR Signaling Pathway / El Acteoside Atenúa el Deterioro de la Memoria de Reconocimiento en Ratas ELCI Mediante la Regulación de la Plasticidad Sináptica y la Vía de Señalización mTOR

SUMMARY: We evaluated the role and mechanism of acteoside in the regulation of memory impairment induced by chronic unpredictable mild stress (CUMS). CUMS was used to induce depression in rats and the successful establishment of CUMS model were verified by forced swimming test and sucrose preference test. The Y-maze test and novel object recognition test assessed memory functions. The structural changes in the cortex and hippocampus were observed by hematoxylin and eosin (HE) staining. Immunofluorescence staining and western blotting determined the protein levels. Y-maze test and novel object recognition test showed that there was memory performance impairment in rats of CUMS group, which was improved by the acteoside treatment. HE staining showed that CUMS exposure damaged the structure in the cortex and hippocampus, while the acteoside treatment alleviated the structural changes. Compared with the control group, the levels of BNDF and CREB in the cortex and hippocampus of the CUMS group were significantly decreased. Acteoside significantly reversed the expressions of these proteins in CUMS rats. Meanwhile, compared with the control group, the levels of p-mTOR and p- P70S6K in the cortex and hippocampus of the CUMS group were significantly increased, and these changes were significantly reversed by acteoside. Nevertheless, the effect of acteoside on mTOR signaling was markedly blocked by rapamycin, a specific inhibitor of mTOR signaling. Acteoside can attenuate memory impairment and ameliorate neuronal damage and synaptic plasticity in depression rats probably via inhibiting the mTOR signaling pathway. Acteoside may serve as a novel reagent for the prevention of depression.

Evaluamos el papel y el mecanismo del acteoside en la regulación del deterioro de la memoria inducido por estrés leve crónico impredecible (ELCI). Se utilizó ELCI para inducir depresión en ratas y el establecimiento exitoso del modelo ELCI se verificó mediante una prueba de natación forzada y una prueba de preferencia de sacarosa. La prueba del laberinto en Y y la prueba de reconocimiento de objetos novedosos evaluaron las funciones de la memoria. Los cambios estructurales en la corteza y el hipocampo se observaron mediante tinción con hematoxilina y eosina (HE). La tinción por inmunofluorescencia y la transferencia Western determinaron los niveles de proteína. La prueba del laberinto en Y y la prueba de reconocimiento de objetos novedosos mostraron que había un deterioro del rendimiento de la memoria en ratas del grupo ELCI, que mejoró con el tratamiento con acteósidos. La tinción con HE mostró que la exposición a ELCI dañó la estructura de la corteza y el hipocampo, mientras que el tratamiento con actósidos alivió los cambios estructurales. En comparación con el grupo de control, los niveles de BNDF y CREB en la corteza y el hipocampo del grupo ELCI disminuyeron significativamente. Acteoside revirtió significativamente las expresiones de estas proteínas en ratas ELCI. Mientras tanto, en comparación con el grupo control, los niveles de p-mTOR y p-P70S6K en la corteza y el hipocampo del grupo ELCI aumentaron significativamente, y estos cambios fueron revertidos significativamente ELCI por el acteoside. Sin embargo, el efecto del acteoside sobre la señalización de mTOR fue notablemente bloqueado por la rapamicina, un inhibidor específico de la señalización de mTOR. El acteoside puede atenuar el deterioro de la memoria y mejorar el daño neuronal y la plasticidad sináptica en ratas con depresión, probablemente mediante la inhibición de la vía de señalización mTOR. Acteoside puede servir como un reactivo novedoso para la prevención de la depresión.

Effects of melatonin on learning and memory abilities of fluoride-exposed offspring rats / 中华地方病学杂志

Objective:To investigate the effect of melatonin (MEL) on learning and memory abilities of fluoride-exposed offspring rats and the role of gut microbiota.Methods:Twelve 8-week-old Sprague-Dawley (SD) rats (8 females and 4 males) with a body weight ranging from 180 to 220 g were selected and divided into control group 1 and fluoride-exposed group 1 using a random number table method, with 6 rats in each group (female ∶ male = 2 ∶ 1). They were free to drink purified water or purified water containing 100 mg/L sodium fluoride, respectively. After 2 months, male and female rats were raised together in cages, and the first postnatal day (PND) of the offspring rats was recorded as PND0. In PND21, the offspring rats of fluoride-exposed group 1 were divided into fluoride-exposed group (Group F, n = 6) and fluoride + MEL group (Group FM, n = 6) using a group design, and continued to be exposed to fluoride through drinking water. The offspring rats of control group 1 were divided into control group (Group C, n = 6) and MEL group ( n = 6). The groups FM and MEL were given 20 mg/kg MEL by gavage, while the groups C and F were given the same dose of normal saline by gavage. In PND60, novel object recognition and Morris water maze tests were used to observe the learning and memory abilities of the offspring rats. Western blotting (WB) was used to detect the expression level of brain derived neurotrophic factor (BDNF) in the hippocampus of the offspring rats. And 16S rDNA sequencing technology was used to detect the changes in the structure and composition of gut microbiota in fecal samples. Results:The results of novel object recognition test showed that there was a statistically significant difference in the discrimination index (DI) among the four groups of offspring rats ( F = 3.95, P = 0.024). The DI in groups C and FM was higher than that of Group F ( P < 0.05). The results of Morris water maze test showed that compared with Group C, the platform-crossing time of the offspring rats of Group F were less and they had a longer time to reach the platform for the first time ( P < 0.05). Compared with Group F, the platform-crossing time of the offspring rats of Group FM were increased and they had a shorter time to reach the platform for the first time ( P < 0.05). The WB results showed that compared with Group C (1.00 ± 0.07), the expression level of BDNF protein in Group F (0.68 ± 0.26) was lower ( P < 0.05). Compared with Group F, the expression level of BDNF protein in Group FM (0.99 ± 0.14) was higher ( P < 0.05). Anosim similarity analysis showed significant differences in the structure and composition of gut microbiota in the four groups of offspring rats ( R = 0.395 062, P = 0.002). The distribution characteristics of gut microbiota species showed that at the phylum level, compared with Group C, the relative abundance of Bacteroidetes in Group F increased from 14.26% to 37.00%, and the relative abundance of Firmicutes decreased from 68.78% to 45.95%. Compared with Group F, the relative abundance of Firmicutes in Group FM increased from 45.95% to 65.26%, and the relative abundance of Bacteroidetes decreased from 37.00% to 23.00%. At the genus level, compared with Group C, the relative abundance of Lactobacillus, Dubosiella, HT002 and UCG-005 in Group F was lower, while the relative abundance of unclassified Muribaculaceae was higher. Compared with Group F, the relative abundance of Lactobacillus, Dubosiella, HT002 and UCG-005 in Group FM was higher, while the relative abundance of unclassified Muribaculaceae was lower. The results of linear discriminant analysis revealed that the Candidatus-Saccharimonas and Incertae-Sedis were significantly enriched in Group C, unclassified Muribaculaceae and Muribaculum were significantly enriched in Group F, and Allorhizobium- Neorhizobium- Pararhizobium- Rhizobium were significantly enriched in Group FM. Conclusion:MEL can improve the learning and memory impairment of offspring rats induced by fluoride exposure by changing the structure and composition of gut microbiota.

Correlation between abnormal thalamic functional connectivity and memory decline in patients with end-stage renal disease undergoing maintenance hemodialysis / 西安交通大学学报(医学版)

【Objective】 To explore the correlation between abnormal thalamic functional connectivity (FC) and memory loss in maintenance hemodialysis patients with end-stage renal disease (ESRD). 【Methods】 An auditory verbal learning test (AVLT-H) was conducted on 22 patients with ESRD and 28 age-, sex-, and education-matched healthy controls (HC) to evaluate memory function. After that, resting-state functional magnetic resonance imaging (rs-fMRI) data were gathered, and a whole-brain FC analysis centered on the thalamus was executed to discern variations in thalamic FC between the two groups. Finally, Pearson and Spearman correlation analyses were carried out. 【Results】 Compared to the HC group, the ESRD group exhibited notably lower scores in IR-S (P=0.002), SR-S (P<0.001), and LR-S (P=0.005). Concurrently, the ESRD group demonstrated diminished FC of the right thalamus with the left superior frontal gyrus, the left parietal lobule, the right suproccipital gyrus, the right anterior cuneus, and the right middle frontal gyrus (P<0.05, TFCE correction). Additionally, reduced FC were observed between the left thalamus and the left gyrus rectus, the left parietal lobule, and the right parietal lobule in the ESRD group (P<0.05, TFCE correction). Moreover, the FC values between the left thalamus and the left gyrus rectus in the ESRD group displayed significant negative correlations with IR-S (r=-0.499), SR-S (r=-0.458), and LR-S (r=-0.455) (all P<0.05). 【Conclusion】 Memory impairment is evident in ESRD patients undergoing maintenance hemodialysis, and it appears to be intricately linked to anomalous FC within the left thalamus and the left gyrus rectus. These findings offer potential imaging markers for monitoring memory dysfunction in individuals with ESRD.

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.

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.

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.

ⅣMep⁃S as a novel dual⁃binding AChEI to ameliorate scopolamine⁃induced learning and memory impairment in mice / 安徽医科大学学报

Objective @#To explore the effect of ( - ) Ⅳmeptazinol⁃serotonin hybrid , [( - ) ⅣMep⁃S] on scopolamineinduced learning and memory impairment in mice.@*Methods@#The binding of ( - ) ⅣMep⁃S and hAChE was analyzed by molecular docking. The effect of ( - ) ⅣMep⁃S on AChE activity was observed in vivo and in vitro. The effect of ( - ) ⅣMep⁃S on learning and memory impairment induced by scopolamine was examined in Morris water maze test in mice. The effect of ( - ) ⅣMep⁃S on the motor behaviors of mice was detected by open field test. @*results@#Molecular docking analysis revealed that ( - ) ⅣMep⁃S binded to human AChE. In parallel , ( - ) ⅣMep⁃S overtly inhibited the activity of AChE derived from mouse forebrain and SH⁃SY5Y neuronal cells , and IC50 values were lower than those of the positive control drug rivastigmine. In the Morris water maze test , mice treated with ( - ) ⅣMep⁃S (2. 5 mg/kg) showed significantly reduced latency on day 4 (P < 0. 05) . Moreover, they exhibited significantly greater percentage of distance travelled and percentage of time spent in the target quadrant in the probe trial on day 5 (P < 0. 05) . ( - ) ⅣMep⁃S at 0. 5 mg/kg did not show any significant effects. In addition , ( - ) Ⅳ Mep⁃S inhibited the enhancement of forebrain AChE activity induced by scopolamine (P < 0. 05) . The open field test showed that the effect of ( - ) ⅣMep⁃S on scopolamine⁃induced learning and memory impairment was not due to the difference on the motor behaviors of mice.@*Conclusion@#( - ) ⅣMep⁃S can effectively inhibit AChE activity and ameliorate scopolamineinduced learning and memory impairment in mice.

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.

Gestational dexamethasone exposure impacts hippocampal excitatory synaptic transmission and learning and memory function with transgenerational effects

The formation of learning and memory is regulated by synaptic plasticity in hippocampal neurons. Here we explored how gestational exposure to dexamethasone, a synthetic glucocorticoid commonly used in clinical practice, has lasting effects on offspring's learning and memory. Adult offspring rats of prenatal dexamethasone exposure (PDE) displayed significant impairments in novelty recognition and spatial learning memory, with some phenotypes maintained transgenerationally. PDE impaired synaptic transmission of hippocampal excitatory neurons in offspring of F1 to F3 generations, and abnormalities of neurotransmitters and receptors would impair synaptic plasticity and lead to impaired learning and memory, but these changes failed to carry over to offspring of F5 and F7 generations. Mechanistically, altered hippocampal miR-133a-3p-SIRT1-CDK5-NR2B signaling axis in PDE multigeneration caused inhibition of excitatory synaptic transmission, which might be related to oocyte-specific high expression and transmission of miR-133a-3p. Together, PDE affects hippocampal excitatory synaptic transmission, with lasting consequences across generations, and CDK5 in offspring's peripheral blood might be used as an early-warning marker for fetal-originated learning and memory impairment.

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.

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.

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 .

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

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.

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.

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