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1.
China Pharmacy ; (12): 1198-1203, 2022.
Article in Chinese | WPRIM | ID: wpr-924072

ABSTRACT

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 .

2.
Article in Chinese | WPRIM | ID: wpr-924058

ABSTRACT

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.

3.
Article in Chinese | WPRIM | ID: wpr-909520

ABSTRACT

Objective:To investigate the effect of postsynaptic density-95(PSD-95)on long-term learning and memory impairment in neonatal rats induced by sevoflurane anesthesia.Methods:A total of 54 SD rats aged 7 days of SPF grade were randomly divided into 3 groups: control group (exposed to air), model group (exposed to 2.1% sevoflurane, 4 h/d, consecutive 3 days) and PSD-95 inhibitor group (inhaled sevoflurane+ intraperitoneal injection NA-1, consecutive 5 days), with 18 rats in each group.Morris water maze test and new object recognition test were used to detect the ability of visuospatial learning and memory and recognition memory of rats in each group.RT-qPCR was used to detect the mRNA levels of kalirin, Rac1 and PSD-95 in rat hippocampus.The expressions of kalirin, Rac1, PSD-95 and apoptosis related proteins Caspase-3, Bcl-2 and Bax in rat hippocampus were detected by Western blot.The expression levels of kalirin and Rac1 in hippocampus were detected by immunohistochemistry.SPSS 23.0 software was used for statistical analysis.Repeated measurement ANOVA and one-way ANOVA was used for comparing among groups.Results:Repeated measurement ANOVA showed that in the water maze test, the interaction between time and group of platform seeking latency and swimming distance of the three groups were significant ( Ftime×group=36.539, 41.548, both P<0.01). Simple effect analysis showed that the platform latency and swimming distance in the model group from day 2 to 6 were longer than those in the control group (platform latency from day 2 to 6: t=14.039, 17.147, 13.155, 13.831, 27.247, all P<0.01; swimming distance from day 2 to 6: t=10.122, 20.987, 7.267, 10.011, 8.121, all P<0.01). Compared with the model group, from day 2 to 6, the platform latencies of PSD-95 inhibitor group were prolonged( t=7.948, 14.768, 11.582, 12.832, 24.346, all P<0.01) and the swimming distances were increased( t=8.235, 24.325, 11.234, 12.031, 7.036, all P<0.01). The new object recognition test found that the new object exploration time in the model group was significantly longer than that in the control group ((21.30±2.27)s, (19.21±1.42)s, t=1.843, P<0.01), and the new object exploration time in the PSD-95 inhibitor group was significantly longer than that in the model group ((26.83±2.13)s, t=4.844, P<0.01). The difference index of novel objects in the model group was significantly lower than that in the control group ((0.41±0.12), (0.59±0.10), t=3.416, P<0.01), and the difference index of novel objects in the PSD-95 inhibitor group was significantly lower than that in the model group ((0.37±0.08), t=0.696, P<0.05). The qRT-PCR results showed that the expressions of Rac1, kalirin and PSD-95 mRNA in the model group were significantly lower than those in the control group ( t=9.969, 3.954, 6.561, P<0.05), and the expressions of Rac1, kalirin and PSD-95 mRNA in the PSD-95 inhibitor group were significantly lower than those of the model group ( t=2.132, 2.251, 3.502, all P<0.05). Immunohistochemistry results showed that the kalirin in the hippocampus CA1 area of the model group was significantly lower than that in the control group((8.18±1.94) vs (15.47±3.35), t=11.47, P<0.01), and kalirin in the PSD-95 inhibitor group was significantly lower than that in the model group((4.98±1.53), t=10.28, P<0.01); Rac1 in the model group was significantly lower than that in the control group ((3.72±1.53), (8.17±2.91), t=6.76, P<0.01), and the Rac1 in the PSD-95 inhibitor group(2.73±0.37) was significantly lower than the model group ( t=4.72, P<0.05). Western blot results showed that Caspase-3((1.37±0.16) vs (0.54±0.01), t=5.71, P<0.01) and Bax((1.87±0.31) vs (1.23±0.25), t=12.01, P<0.01) protein levels in the model group were significantly higher than those in the control group.Caspase-3 and Bax protein levels in the PSD-95 inhibitor group were significantly higher than those in model group (Caspase-3: (1.79±0.17), t=9.87, P<0.01; Bax: (2.19±0.21), t=16.19, P<0.01). The Bcl-2 protein level in the model group was significantly lower than that of the control group ((1.22±0.21) vs (1.96±0.38), t=11.92, P<0.01). And the Bcl-2 protein level in the PSD-95 inhibitor group (1.01±0.19) was significantly lower than that in the model group ( t=10.73, P<0.01). Conclusion:Sevoflurane anesthesia can damage the long-term learning and memory function and reduce the expression of PSD95 protein in neonatal rats.Inhibiting the expression of PSD95 can aggravate this damage, which may be related to the synaptic plasticity and apoptosis of neurons involved in PSD95.

4.
Article in Chinese | WPRIM | ID: wpr-906111

ABSTRACT

Objective:To investigate the effect of total ginsenoside ginseng root on the learning and memory impairment and anxiety of hindlimb suspension rats by detecting the performance of rats in the water maze, elevated plus maze, and the expression of hypothalamic-pituitary-adrenal (HPA) axis, inflammatory factors and tryptophan pathway related factors through the intervention of ginsenosides in hindlimb suspension rats. Method:The Wistar male rats were divided into normal group, hindlimb suspension model group, Huperzine A group (0.1 mg·kg<sup>-1</sup>), and total ginsenoside ginseng root low and high dose groups (100, 200 mg·kg<sup>-1</sup>), with 8 rats in each group. Except for the normal group, the rats in the other groups maintained a -30° hindlimb suspension state for 24 h. The normal group and the model group received intragastric administration of 10 mL·kg<sup>-1</sup> pure water . After 28 days of continuous administration, the water maze and elevated plus maze behavioral tests were performed. After the tests, blood was taken from the abdominal aorta, and the rat brain cortex was peeled off on ice, quenched with liquid nitrogen, and stored at -80 ℃ for later use. LC-MS/MS was used to detect neurotransmitter levels of dopamine, acetylcholine, glutamate, <italic>γ</italic>-aminobutyric acid and tryptophan pathway metabolites (tryptophan, 5-hydroxytryptamine, 5-hydroxyindoleacetic acid, kynurenine, 3-hydroxykynurenine, and kynurenine) in rat brain cortex. An enzyme-linked immunosorbent assay (ELISA) kit was used to detect the levels of inflammatory factors interleukin-6 (IL-6), interleukin-10 (IL-10, the HPA axis-related hormone corticotropin (ACTH), and the level of corticosterone (CORT). Result:Compared with the normal group, the escape latency in the water maze significantly increased, the number of crossings was significantly reduced, and the number of open-arm entry and the percentage of open-arm entry were significantly reduced in the elevated plus maze in model group (<italic>P</italic><0.05,<italic> P</italic><0.01), the content of dopamine, acetylcholine, glutamic acid, and <italic>γ</italic>-aminobutyric acid in the cortex decreased, kynurenine and kynurenic acid showed an upward trend, 3-hydroxykynurenine, 5-hydroxytryptamine, 5-hydroxyindole acetic acid showed a downward trend, and the levels of IL-6, IL-10, ACTH, and CORT in the serum significantly increased (<italic>P</italic><0.05, <italic>P</italic><0.01). Compared with the model group of rats, total ginsenoside ginseng root low and high dose groups group reduced the avoidance latency in the water maze, and increased the number of crossings and the number of open arms of the elevated plus maze, dopamine, acetylcholine, glutamate, and <italic>γ</italic>-aminobutyl content increased, while kynurenine and kynurenic acid showed a downward trend, 3-hydroxykynurenine, serotonin, and 5-hydroxyindole acetic acid showed an upward trend, and IL-6, IL-10, ACTH, and CORT factor levels were down-regulated(<italic>P</italic><0.05, <italic>P</italic><0.01). Conclusion:Hindlimb suspension for 28 days in simulated microgravity can impair the learning and memory ability of rats and cause anxiety-like behaviors. Total ginsenoside ginseng root can improve their learning and memory impairment and anxiety-like behaviors. The mechanism may be mainly related to inhibiting body inflammation and regulating HPA axis imbalance.

5.
Article in Chinese | WPRIM | ID: wpr-906076

ABSTRACT

Objective:To explore the underlying protective mechanism of Kaixinsan on learning, memory, and synaptic function in APP/PS1 mice. Method:Sixty APP/PS1 mice were randomly divided into a model group, a donepezil (2 mg·kg<sup>-1</sup>·d<sup>-1</sup>) group, and low- (0.7 g·kg<sup>-1</sup>·d<sup>-1</sup>), medium- (1.4 g·kg<sup>-1</sup>·d<sup>-1</sup>), and high-dose (2.8 g·kg<sup>-1</sup>·d<sup>-1</sup>) Kaixinsan groups, and the wild-type mice of the same age in the same litter were assigned to the normal group, with 12 mice in each group. After continuous intragastric administration for two months, the Morris water maze experiment was performed. The ultrastructure of hippocampal neurons was observed by transmission electron microscopy. The colorimetric assay was used to detect serum content of acetylcholine (ACh), choline acetyltransferase (ChAT), acetylcholinesterase (AChE), and levels of hippocampal reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px). Real-time fluorescence-based quantitative polymerase chain reaction (Real- time PCR) was used to detect the mRNA expression of hippocampal brain-derived neurotrophic factor (BDNF), beta-nerve growth factor (NGFB), discs large homolog (DLG)2, DLG4, and synaptophysin (SYP). Result:Compared with the normal group, the model group showed prolonged escape latency, reduced number of crossing platforms, shortened stay in the target quadrant (<italic>P</italic><0.01), decreased number of mitochondria with different shapes and irregular arrangement, some swollen and deformed mitochondria with broken mitochondrial cristae, endolysis, and cytoplasm vacuole, and more cell debris. Additionally, the model group also displayed reduced serum levels of ACh and ChAT, increased AChE (<italic>P</italic><0.01), elevated hippocampal ROS and MDA (<italic>P</italic><0.05,<italic>P</italic><0.01), declining SOD and GSH-Px (<italic>P</italic><0.01), and diminished hippocampal BDNF, NGFB, DLG2, DLG4, and SYP mRNA levels (<italic>P</italic><0.05,<italic>P</italic><0.01). Compared with the model group, the donepezil group, and the medium- and high-dose Kaixinsan groups showed shortened escape latency, increased number of crossing platforms, prolonged stay in the target quadrant (<italic>P</italic><0.05,<italic>P</italic><0.01), improved mitochondrial damage with a regular shape (mainly oval shape), relieved mitochondrial swelling and deformation, and clear mitochondrial cristae. Furthermore, the donepezil group, and the medium- and high-dose Kaixinsan groups also exhibited increased serum ACh and ChAT levels (<italic>P</italic><0.05,<italic>P</italic><0.01), blunted AChE activity (<italic>P</italic><0.05), reduced hippocampal ROS level (<italic>P</italic><0.05,<italic>P</italic><0.01), declining MDA level (<italic>P</italic><0.05), potentiated SOD and GSH-Px activities, and up-regulated hippocampal BDNF, NGFB, DLG2, DLG4, and SYP mRNA levels (<italic>P</italic><0.05,<italic>P</italic><0.01). In the low-dose Kaixinsan group, the stay time in the target quadrant was prolonged and the expression of hippocampal SYP mRNA was elevated significantly (<italic>P</italic><0.05). There was no statistical difference in swimming speed between the groups. Conclusion:Kaixinsan can improve the learning and memory ability of APP/PS1 mice by increasing the expression of synaptic plasticity-related proteins, reducing the ultrastructural damage to hippocampal neurons, resisting oxidative stress, and regulating cholinergic neurotransmitters, thereby exerting neuroprotective effects.

6.
Article in Chinese | WPRIM | ID: wpr-906066

ABSTRACT

Objective:To explore the effects of Yuanzhisan (YZS) containing Ginseng Radix et Rhizoma (YZSR) or Codonopsis Radix (YZSD) on memory disorder based on network and experimental pharmacology. Method:The active components and targets of YZS were retrieved from the component database and literature, and the targets of memory disorder from the disease databases. The intersection targets revealed by Veen diagram were subjected to pathway analysis. The common active components of YZSR and YZSD were molecularly docked onto the core targets. Scopolamine hydrobromide was used to establish the memory disorder model, which was employed in the behavioral experiments for evaluating the effect of YZSR and YZSD on memory disorder. Result:There existed 33 active components for Ginseng Radix et Rhizoma and 31 for Codonopsis Radix, with four common active components and 380 common targets. YZSR contained 85 active components and 790 drug targets, and YZSD 81 active components and 781 drug targets. The mapping of 425 memory disorder targets with those of YZSD and YZSD yielded 133 and 130 intersection targets, respectively. The metabolic pathways involved calcium ion signaling pathway, hypoxia-inducible factor-1 (HIF-1) signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway, etc. As revealed by molecular docking, the binding energy of common active components to the targets was negative, and the binding effect of frutinone A was the best. Behavioral experiment results showed that both YZSR and YZSD alleviated the memory disorder. In the step-down test, the number of errors in the YZSD group was significant lower than that in the model group (<italic>P</italic><0.01). In Morris water maze test, the movement distance of the YZSD group was remarkably shortened in comparison with that of the model group (<italic>P</italic><0.05). In the open field test, the movement distances of both the YZSR and YZSD group were shortened in contrast to that in the normal group (<italic>P</italic><0.05). Conclusion:YZS had a certain effect on memory disorder. There are similarities and differences between YZSR and YZSD in the treatment of memory disorder.

7.
Article in Chinese | WPRIM | ID: wpr-905988

ABSTRACT

Objective:To observe the effects of Huazhuo Jiedu Shugan Prescription (HZJDSG) on learning, memory, and the expression of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase-3<italic>β</italic> (GSK-3<italic>β</italic>) pathway-related proteins in epileptic rats, and to explore its possible mechanism. Method:Forty-eight SPF male SD rats were randomly divided into a normal group, a model group, a sodium valproate (0.19 g·kg<sup>-1</sup>) group, and low- (2.7 g·kg<sup>-1</sup>), medium- (5.4 g·kg<sup>-1</sup>), and high-dose (10.8 g·kg<sup>-1</sup>) HZJDSG groups, with eight rats in each group. The normal group received 0.9% sodium chloride solution (0.035 g·kg<sup>-1</sup>) by intraperitoneal injection, and the other five groups received pentetrazol (PTZ) at the same dose to induce a chronic epilepsy model for a total of 14 times. The drug groups received corresponding drugs and the normal group and the model group received 0.9% sodium chloride solution at the same volume once a day for 28 days. During the drug intervention period, epilepsy was maintained in each modeling group by intraperitoneal injection of PTZ on day 7, 14, 21, and 28. The behavioral changes of rats were observed by Morris water maze and the pathomorphological changes of rat hippocampal neurons by hematoxylin-eosin (HE) staining. The protein expression of phosphorylation Akt(p-Akt)and p-GSK-3<italic>β</italic> was detected by immunohistochemistry and the protein expression of PI3K, Akt, p-Akt, GSK-3<italic>β</italic>, and p-GSK-3<italic>β</italic> by Western blot. Result:Compared with the normal group, the model group showed prolonged platform finding time (<italic>P</italic><0.01), reduced number of platform crossings (<italic>P</italic><0.01), structural damage of neurons in the CA1 region of the hippocampus, down-regulated protein expression of p-Akt and p-GSK-3<italic>β </italic>in the CA1 region of the hippocampus (<italic>P</italic><0.05), and reduced relative expression of PI3K, p-Akt, and p-GSK-3<italic>β</italic> in the hippocampus (<italic>P</italic><0.01). Compared with the model group, the sodium valproate group and the HZJDSG groups showed shortened platform finding time (<italic>P</italic><0.01) and improved neuronal structure in the CA1 region of the hippocampus, while the sodium valproate group and the high- and medium-dose HZJDSG groups exhibited increased number of platform crossings (<italic>P</italic><0.01), up-regulated protein expression of p-Akt and p-GSK-3<italic>β</italic> in the CA1 region of the hippocampus (<italic>P</italic><0.05), and elevated relative expression of PI3K, p-Akt, and p-GSK-3<italic>β</italic> (<italic>P</italic><0.01). Conclusion:HZJDSG can improve the learning and memory of epileptic rats, and its antiepileptic effect may be achieved by the activation of PI3K/Akt/GSK-3<italic>β</italic> pathway-related proteins.

8.
China Occupational Medicine ; (6): 147-152, 2021.
Article in Chinese | WPRIM | ID: wpr-923227

ABSTRACT

OBJECTIVE: To explore the effects of high temperature on learning and memory ability, behavioral activity, and fatigue as well as the intervention effect of compound nutrients on the exercising mice. METHODS: Thirty specific pathogen-free healthy male Kunming mice were randomly divided into the normal-temperature exercise, high-temperature exercise, and high-temperature exercise supplement groups, with 10 mice in each group. The mice in these three groups performed treadmill exercise for one hour every day, six days per week, and continued for four weeks. The mice in the high-temperature exercise supplement group were fed with 0.3 mL of compound nutrients 30 minutes before each treadmill exercise, whereas the mice in the normal-temperature exercise and the high-temperature exercise groups were fed with an equal volume of distilled water. At the end of the treadmill exercise, the mice were subjected to experiments on their neurological behaviors. The serum of mice in each group were collected to detect the lactic acid level, urea nitrogen level, and creatine kinase activity. The liver and gastrocnemius muscle tissues were then taken for detecting the levels of liver glycogen and muscle glycogen.RESULTS: Compared with the mice in the normal-temperature exercise group, the escape latency of the mice in the high-temperature exercise group was prolonged(P<0.05), whereas the number of platform crossings, percentage of target quadrant time, and distance were reduced(all P<0.05). Compared with the mice in the high-temperature exercise group, the escape latency of the mice in the high-temperature exercise supplement group was shortened(P<0.05), whereas the number of platform crossings, percentage of target quadrant time, and distance were increased(all P<0.05). Compared with the mice in the normal-temperature exercise group, the first fall time and grip strength of the mice in the high-temperature exercise group were reduced(all P<0.05), whereas the number of falls was increased(P<0.05). Compared with the mice in the high-temperature exercise group, the first fall time and grip strength of the mice in the high-temperature exercise supplement group were increased(all P<0.05), whereas the number of falls was reduced(P<0.05). Compared with the mice in the normal-temperature exercise group, the serum lactic acid level, urea nitrogen level, and creatine kinase activity of the mice in the high-temperature exercise group were increased(all P<0.05), whereas the levels of liver glycogen and muscle glycogen were decreased(all P<0.05). Compared with the mice in the high-temperature exercise group, the serum lactic acid level, urea nitrogen level, and creatine kinase activity of the mice in the high-temperature exercise supplement group were decreased(all P<0.05), whereas the levels of liver glycogen and muscle glycogen were increased(all P<0.05). CONCLUSION: High temperature exercise can lead to decreased learning and memory ability and behavioral activity in mice, resulting in exercise-induced fatigue. Supplemental compound nutrients can prevent these changes.

9.
China Occupational Medicine ; (6): 366-372, 2021.
Article in Chinese | WPRIM | ID: wpr-923201

ABSTRACT

OBJECTIVE: To analyze the relationship between the neurobehavioral functions of individuals exposed to low-level lead and the levels of serum copper-related proteins glutathione S-transferase M1(GSTM1), hypoxia inducible factor-1 alpha(HIF1α), cyclooxygenase 1(COX1) and metallothionein(MT), and to screen biomarkers for changes in neurobehavioral function caused by occupational lead exposure. METHODS: A total of 194 workers who exposed to low-level lead(lead-exposed group) and 120 workers without lead exposure(control group) were selected from a battery factory as the research subjects by judgment sampling method. The inductively coupled plasma-mass spectrometry was used to determine blood lead levels of the two groups, and the State of Mood Scale(POMS) was investigated to assess the emotional state. The computerized neurobehavioral evaluation system in Chinese version 3(NES-C3) was used to test the neurobehavioral ability index(NAI) of related indicators of learning memory and mental activity. Enzyme-linked immunosorbent assay was used to detect the levels of copper-related protein in serum. After using principal component analysis to extract the principal components of emotional state, learning memory and mental activity, multiple linear regression was used to analyze the influencing factors of neurobehavioral function. RESULTS: The blood lead level of the lead-exposed group was increased [(57.15±11.12) vs(177.86±80.04) μg/L, P<0.01], and the incidence of symptoms such as dizziness, memory loss, sleep disturbance, fatigue, weakness, cold sweats in extremities, cold extremities, tingling of extremities, tingling sensation in the distal extremities, tetany, instability of holding things, metallic taste in the mouth, nausea and vomiting, anorexia, constipation, abdominal distension, abdominal pain, toothache/tooth loosening were increased(all P<0.01) compared with the control group. Meanwhile, the scores of tension-anxiety, depression-dejection, fatigue-inertia, anger-hostility, confusion-bewilderment of POMS were increased(all P<0.01), and the scores of vigor-activity were decreased(P<0.01). The NAI of the lead-exposed individuals in the NES-C3 test of 6 indicators(series addition and subtraction, visual retention, memory scanning, listening to digital breadth, visual simple reaction time, target tracking) were lower than that of the control group(all P<0.01). The serum levels of GSTM1 and HIF1α of the lead-exposed group decreased(all P<0.01), and the COX1 and MT levels increased(all P<0.01) compared with the control group. The serum GSTM1, HIF1α, COX1 and MT of the lead-exposed group were correlated with their emotional state, learning and memory and mental activity to varying degrees(all P<0.05). The results of multiple stepwise linear regression showed that serum COX1 level was an independent influencing factor of emotional state(P<0.01), serum GSTM1, COX1 and lead working years were independent influencing factor of learning and memory(all P<0.05), and work length with lead exposure and alcohol consumption was an independent influencing factor of mental activity(all P<0.05). CONCLUSION: Low-level lead exposure can cause central nervous system symptoms in workers, and the change in neurobehavioral function and serum levels of copper-related proteins GSTM1, HIF1α, COX1 and MT. Serum levels of GSTM1 and COX1 can be used as candidate biomarkers for indicating neurobehavioral function caused by lead exposure.

10.
Neuroscience Bulletin ; (6): 1645-1657, 2021.
Article in English | WPRIM | ID: wpr-922643

ABSTRACT

Steroid hormones play important roles in brain development and function. The signaling of steroid hormones depends on the interaction between steroid receptors and their coactivators. Although the function of steroid receptor coactivators has been extensively studied in other tissues, their functions in the central nervous system are less well investigated. In this study, we addressed the function of steroid receptor coactivator 3 (SRC3) - a member of the p160 SRC protein family that is expressed predominantly in the hippocampus. While hippocampal development was not altered in Src3


Subject(s)
Animals , Hippocampus , Long-Term Potentiation , Mice , Neuronal Plasticity , Nuclear Receptor Coactivator 3/genetics , Synapses
11.
Acta Pharmaceutica Sinica B ; (6): 599-608, 2021.
Article in English | WPRIM | ID: wpr-881158

ABSTRACT

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

12.
Article in English | WPRIM | ID: wpr-880327

ABSTRACT

BACKGROUND@#Prenatal stress can cause neurobiological and behavioral defects in offspring; environmental factors play a crucial role in regulating the development of brain and behavioral; this study was designed to test and verify whether an enriched environment can repair learning and memory impairment in offspring rats induced by prenatal stress and to explore its mechanism involving the expression of insulin-like growth factor-2 (IGF-2) and activity-regulated cytoskeletal-associated protein (Arc) in the hippocampus of the offspring.@*METHODS@#Rats were selected to establish a chronic unpredictable mild stress (CUMS) model during pregnancy. Offspring were weaned on 21st day and housed under either standard or an enriched environment. The learning and memory ability were tested using Morris water maze and Y-maze. The expression of IGF-2 and Arc mRNA and protein were respectively measured by using RT-PCR and Western blotting.@*RESULTS@#There was an elevation in the plasma corticosterone level of rat model of maternal chronic stress during pregnancy. Maternal stress's offspring exposed to an enriched environment could decrease their plasma corticosterone level and improve their weight. The offspring of maternal stress during pregnancy exhibited abnormalities in Morris water maze and Y-maze, which were improved in an enriched environment. The expression of IGF-2, Arc mRNA, and protein in offspring of maternal stress during pregnancy was boosted and some relationships existed between these parameters after being exposed enriched environment.@*CONCLUSIONS@#The learning and memory impairment in offspring of prenatal stress can be rectified by the enriched environment, the mechanism of which is related to the decreasing plasma corticosterone and increasing hippocampal IGF-2 and Arc of offspring rats following maternal chronic stress during pregnancy.


Subject(s)
Animals , Cytoskeletal Proteins/metabolism , Female , Gene Expression Regulation , Hippocampus/metabolism , Insulin-Like Growth Factor II/metabolism , Learning , Learning Disabilities/psychology , Male , Memory Disorders/psychology , Nerve Tissue Proteins/metabolism , Pregnancy , Prenatal Exposure Delayed Effects/psychology , Random Allocation , Rats , Rats, Wistar , Social Environment , Stress, Psychological/genetics
13.
Article in Chinese | WPRIM | ID: wpr-877673

ABSTRACT

OBJECTIVE@#To observe the effect of electroacupuncture (EA) pretreatment on hippocampal oxidative stress in aged mice with postoperative cognitive dysfunction (POCD) and explore the relevant mechanism of EA pretreatment on the improvement of learning and memory in POCD aged mice.@*METHODS@#A total of 72 healthy male aged mice were randomized into a blank group, a model group, a medication group and an EA group, 18 mice in each one. In each group, 1-day, 3-day and 7-day subgroups were divided separately, 6 mice in each subgroup. In the EA group, "Baihui" (GV 20) and "Dazhui" (GV 14) were selected and stimulated with EA, using continuous wave (15 Hz, 1 mA), continuously for 30 min, once a day, for 5 days consecutively. In the medication group, 10% minocycline was injected intraperitoneally, 40 mg/kg, once a day, consecutively for 5 days. In the blank and the control group, intraperitoneal injection of 0.9% sodium chloride solution was given with equal dosage. Except the blank group, at the end of intervention, partial hepatectomy was conducted to establish POCD model in the rest groups. Morris water maze test was adopted to evaluate the learning and memory ability of the aged mice. ELISA was used to determine the contents of reactive oxygen species (ROS) and malondialdehyde (MDA) in the hippocampal tissue. Western blot method was applied to detect the protein expressions of superoxide dismutase 1 (SOD 1) and superoxide dismutase 2 (SOD 2) in the hippocampal tissue.@*RESULTS@#Compared with the blank group, the percentage of platform quadrant residence time was obviously reduced in the mice in the model group (@*CONCLUSION@#Electroacupuncture pretreatment at "Baihui" (GV 20) and "Dazhui" (GV 14) may increase the learning and memory ability of POCD aged mice, which is probably related to the decrease of oxidative stress and the strengthening of hippocampal antioxidant capacity.


Subject(s)
Animals , Electroacupuncture , Hippocampus , Male , Memory , Mice , Oxidative Stress , Postoperative Cognitive Complications
14.
Article in Chinese | WPRIM | ID: wpr-873583

ABSTRACT

@#To investigate the effects and possible molecular mechanism of S-oxiracetam(S-ORC) on learning and memory impairment in mice, mice were divided into 5 groups, control group, model group, high-dose of S-ORC (0.96 g/kg), medium-dose of S-ORC (0.48 g/kg) and low-dose of S-ORC (0.24 g/kg) treatment groups.Step-down test and Y-maze test were used to investigate the effects of S-ORC on the brain.The results of step-down test revealed that the mice in high and medium-dose groups could significantly decrease the reaction time, fault times and prolong the incubation periods of memory compared with the model group.Compared with the model group, the fault times of mice in high and medium-dose groups decreased significantly and the right times to find the safety increased significantly in Y-maze test.Furthermore, through treatment with S-ORC (high and medium-dose groups), the content of Ach in mice brain was significantly higher than that in model group, and the level of AChE decreased significantly.The above results suggest that the underlying mechanism of S-ORC on learning and memory impairment in mice may include the amelioration of the central cholinergic nervous system.

15.
Article in Chinese | WPRIM | ID: wpr-873015

ABSTRACT

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.

16.
Article in Chinese | WPRIM | ID: wpr-872647

ABSTRACT

Objective:To explore the effect of Anmeidan (AMD) on the learning and memory levels of sleep deprived rats through mitochondrial mediated hippocampal neuronal apoptosis pathway. Method:Forty-eight SD rats were randomly divided into blank group, model group, low, medium, high-dose AMD groups (4.86, 9.72, 19.44 g·kg-1·d-1) and estazolam group (0.1 mg·kg-1·d-1). Insomnia model was prepared by self-made sleep deprivation box for 14 days. Morris water maze was used to detect learning and memory levels, enzyme-linked immunosorbent assay (ELISA) was used to detect the expressions of cytochrome C (Cyt-C), cysteine aspartic acid protease-3 (Caspase-3) in hippocampus. Transmission electron microscopy (TEM) was used to observe the morphological structure of mitochondria in hippocampus. Protein and mRNA expressions of Cyt-C, Caspase-3, Bcl-2, Bax were detected by immunofluorescence (IF) and Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) respectively. Result:In the model group, the incubation period of the platform and the total distance of swimming and the time of first arriving platform were prolonged, the number of platform crossing and the time of target quadrant movement were reduced, protein and mRNA expressions of Bcl-2 dropped, protein and mRNA expressions of Bax increased (P<0.01), and mitochondrial structure was abnormal with crista fracture, swelling and deformation. And protein and mRNA expressions of Cyt-C, Caspase-3 increased significantly (P<0.01). Low, medium and high-dose AMD groups could improve levels of space exploration and navigation of SD rats (P<0.01), increase protein and mRNA expressions of Bcl-2, decrease protein and mRNA expressions of Bax, improve the damage of mitochondria, and decrease the protein and mRNA expressions of Cyt-C, Caspase-3 (P<0.01). Conclusion:AMD can improve the learning and memory levels of SD rats, the effect is related to the mitochondrial mediated hippocampal neuronal apoptosis pathway and decrease of Cyt-C and Caspase-3 expressions.

17.
Article in Chinese | WPRIM | ID: wpr-905783

ABSTRACT

Objective:To observe the effect of electroacupuncture at Baihui (DU20) and Shenting (DU24) acupoints on white matter fiber and learning-memory function in rats with vascular dementia (VD). Methods:Sprague-Dawley rats were randomly divided into operation group and sham group (n = 8). The operation group accepted two-vessel occlusion, while the sham group only separated the bilateral common carotid arteries without ligation. The rats modeled successfully were randomly divided into model group (n = 8), non-acupoint group (n = 8) and electroacupuncture group (n = 8). The electroacupuncture group accepted electroacupuncture at Baihui and Shenting, and the non-acupoint group accepted electroacupuncture at axillary non-acupoint, once a day for 28 days. All the rats were tested with object recognition test before and after intervention, while the white matter fibers were observed with Diffusion Tensor Imaging. Results:Compared with the sham group, the preference coefficients of the model group, the non-acupoint group and the electroacupuncture group decreased before intervention (P< 0.05), and there was no significant difference among the later three groups (P> 0.05). The preference coefficients increased in the electroacupuncture group compared with the model group after intervention (P< 0.05). The fractional anisotropy (FA) of corpus callosum, cingulate gyrus and hippocampus decreased in the model group, the non-acupoint group and the electroacupuncture group compared with the sham group before intervention. FA of hippocampus, cingulate gyrus, corpus callosum and external capsule increased in the electroacupuncture group compared with the model group after intervention. Conclusion:Electroacupuncture at Baihui and Shenting can improve learning-memory function of VD rats, which may be related with repairment of white matter fibers in prefrontal cortex, hippocampus and others.

18.
Article in Chinese | WPRIM | ID: wpr-905475

ABSTRACT

Objective:To investigate the effects of electroacupuncture at Baihui (DU20) and Shenting (DU24) on brain function of APP/PS1 mice. Methods:Sixteen 4-month-old APP/PS1 mice in the same litter were randomly divided into model group (n = 8) and electroacupuncture group (n = 8). Eight transgenic negative mice in the same litter were as control group. The electroacupuncture group accepted electroacupuncture at Baihui and Shenting for 16 weeks. They were assessed with Object Recognition Test before and after intervention, and observed under small animal functional magnetic resonance imaging with regional homogeneity (ReHo) analysis. Results:Compared with the control group, the discrimination ratio decreased in the model group after intervention (P < 0.05), while it increased in the electroacupuncture group compared with that in the model group (P < 0.05). Compared with the control group, ReHo of right basal forebrain and left hippocampus decreased in the model group before intervention. Compared with the control group, ReHo decreased in bilateral hippocampus group and increased in retrosplenial cortex in the model group after intervention; while it increased in bilateral hippocampus and motor cortex and decreased in anterior cingulate gyrus in the electroacupuncture group compared with that in the model group. Conclusion:Electroacupuncture at Baihui and Shenting may delay the decline of learning and memory ability in Alzheimer's disease model mice, which may relate to the regulation of functional activities in hippocampus.

19.
China Occupational Medicine ; (6): 141-146, 2020.
Article in Chinese | WPRIM | ID: wpr-881876

ABSTRACT

OBJECTIVE: To study the effect of sub-chronic aluminum exposure on synaptic plasticity in the hippocampus of rats and to explore the mechanism of phosphatidylinositol 3 kinase(PI3 K)/protein kinase B(AKT)/rapamycin target protein(mTOR) signaling pathway. METHODS: Specific pathogen free adult healthy male SD rats were randomly divided into control group and low-, medium-and high-dose groups based on body weight, with 10 rats in each group. Rats were treated with maltol aluminum solution at the concentrations of 0, 10, 20 and 40 μmol/kg body weight by intraperitoneal injection, 5 days per week for 3 months. After the exposure, rats were weighed. Morris water maze was used to test the learning and memory ability, and the two-electrode binding technique was used to record the long-term potentiation(LTP) amplitude in the hippocampus CA1 area of rats. The protein expression of PI3 K, AKT and mTOR in rat hippocampus tissues was detected by Western blot. RESULTS: After the exposure, the body weights of rats in the medium-and high-dose groups were lower than that of the control group(P<0.05). The results of the positioning navigation experiment showed that the escape latencies of the rats in the medium-and high-dose groups were shorter than that in the control group during the 2 nd to 4 th days of the experiment(P<0.05). The results of space exploration experiments showed that there was no statistical difference on the target quadrant retention time and the number of crossing the platform among the 4 groups(P>0.05). At 1, 30, and 60 min after high-frequency stimulation, the LTP amplitudes in the hippocampus CA1 area of the aluminum-treated groups were lower than that of the control group at the same time point(P<0.05), and the LTP amplitudes of hippocampus CA1 area of rats decreased with the increase of maltol aluminum exposure dose(P<0.01). The relative expression of PI3 K, AKT and mTOR protein in the hippocampus tissues of the aluminum-treated groups was lower than that of the control group(P<0.05), and the relative expression of the above three proteins decreased with the increase of the maltol aluminum exposure dose(P <0.01). CONCLUSION: Sub-chronic aluminum exposure could lead to dose-dependent inhibition of hippocampus synaptic plasticity in rats, thereby impairing the spatial learning ability of rats. This process may be related to inhibition of PI3 K/AKT/mTOR signaling pathway by aluminum.

20.
China Occupational Medicine ; (6): 30-34, 2020.
Article in Chinese | WPRIM | ID: wpr-881860

ABSTRACT

OBJECTIVE: To investigate the persistent damage of learning and memory ability after the cessation of sub-chronic manganese(Mn)-exposure in rats. METHODS: Specific pathogen free weaning male SD rats were randomly divided into control group and low-, medium-and high-dose groups based on body weight, with 6 rats in each group. Rats were intraperitoneally injected with Mn chloride(MnCl_2·4 H_2O) at the concentrations of 0, 5, 10, or 20 mg/kg body weight, 5 days per week for 6 weeks and continued to be observed for 12 weeks after the cessation of Mn-exposure. During the experiment, the body mass of the rats was weighed. Learning and memory ability was evaluated by a Morris water-maze task at the 6 th weeks of Mn-exposure(cessation of Mn-exposure of week 0), the 6 th and 12 th week of the cessation of Mn-exposure. The organ coefficients of heart, liver, spleen, kidney and testicles were evaluated after the cessation of Mn-exposure on week 12. RESULTS: The body mass of the high-dose group was lower than that of the other 3 groups(P<0.05) at the 4 th and 6 th week of Mn-exposure and the 2 nd week of the cessation of Mn-exposure. There was no significant difference in body mass between the groups(P>0.05) on the 12 th week of the cessation of Mn-exposure. The escape latency of high-dose group was higher than that of the control group(P<0.05), and the number of platform crossings in the low-, medium-and high-dose groups were fewer than that in the control group(P<0.05) after the cessation of Mn-exposure. The escape latency was shorter and the numbers of platform crossings were higher on the 6 th and 12 th week of the cessation of Mn-exposure(P<0.05) when compared with that of the 6 th week of Mn-exposure rats. There was no statistical significance in the organ coefficients of heart, liver, spleen, kidney and testicles among the 4 groups at the 12 th week of the cessation of Mn-exposure in rats(P>0.05).CONCLUSION: Sub-chronic Mn exposure can impair learning and memory ability of rats, and the damage persists after the cessation of Mn-exposure.

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