Effects of S-oxiracetam on learning and memory impairment in mice / 中国药科大学学报

@#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.

Protective effect of CD73 inhibitor α, ß-methylene ADP against amyloid-ß-induced cognitive impairment by inhibiting adenosine production in hippocampus

BACKGROUND: Alzheimer's disease (AD) is a chronic, progressive neurodegenerative disease. Recent studies have reported the close association between cognitive function in AD and purinergic receptors in the central nervous system. In the current study, we investigated the effect of CD73 inhibitor α, ß-methylene ADP (APCP) on cognitive impairment of AD in mice, and to explore the potential underlying mechanisms. RESULTS: We found that acute administration of Aß1­42 (i.c.v.) resulted in a significant increase in adenosine release by using microdialysis study. Chronic administration of APCP (10, 30 mg/kg) for 20 d obviously mitigated the spatial working memory impairment of Aß1­42-treated mice in both Morris water maze (MWM) test and Y-maze test. In addition, the extracellular adenosine production in the hippocampus was inhibited by APCP in Aß-treated mice. Further analyses indicated expression of acetyltransferase (ChAT) in hippocampus of mice of was significantly reduced, while acetylcholinesterase (AChE) expression increased, which compared to model group. We observed that APCP did not significantly alter the NLRP3 inflammasome activity in hippocampus, indicating that anti-central inflammation seems not to be involved in APCP effect. CONCLUSIONS: In conclusion, we report for the first time that inhibition of CD73 by APCP was able to protect against memory loss induced by Aß1­42 in mice, which may be due to the decrease of CD73-driven adenosine production in hippocampus. Enhancement of central cholinergic function of the central nervous system may also be involved in the effects of APCP.

The Effects of Donepezil, an Acetylcholinesterase Inhibitor, on Impaired Learning and Memory in Rodents

A previous study in humans demonstrated the sustained inhibitory effects of donepezil on acetylcholinesterase (AChE) activity; however, the effective concentration of donepezil in humans and animals is unclear. This study aimed to characterize the effective concentration of donepezil on AChE inhibition and impaired learning and memory in rodents. A pharmacokinetic study of donepezil showed a mean peak plasma concentration of donepezil after oral treatment (3 and 10 mg/kg) of approximately 1.2 ± 0.4 h and 1.4 ± 0.5 h, respectively; absolute bioavailability was calculated as 3.6%. Further, AChE activity was inhibited by increasing plasma concentrations of donepezil, and a maximum inhibition of 31.5 ± 5.7% was observed after donepezil treatment in hairless rats. Plasma AChE activity was negatively correlated with plasma donepezil concentration. The pharmacological effects of donepezil are dependent upon its concentration and AChE activity; therefore, we assessed the effects of donepezil on learning and memory using a Y-maze in mice. Donepezil treatment (3 mg/kg) significantly prevented the progression of scopolamine-induced memory impairment in mice. As the concentration of donepezil in the brain increased, the recovery of spontaneous alternations also improved; maximal improvement was observed at 46.5 ± 3.5 ng/g in the brain. In conclusion, our findings suggest that the AChE inhibitory activity and pharmacological effects of donepezil can be predicted by the concentration of donepezil. Further, 46.5 ± 3.5 ng/g donepezil is an efficacious target concentration in the brain for treating learning and memory impairment in rodents.

Therapeutic effect of curcumin and hippocampal brain-derived neurotrophic factor on a rat model of Alzheimer’s disease / 西安交通大学学报(医学版)

ABSTRACT:Objective To study the effect of curcumin on the learning and memory ability in a rat model of Alzheimer’s disease (AD).Methods AD rat model was prepared using intraventricular injection of Aβ1-42. Curcumin was acutely (single injection before the behavioral tests)or chronically (injected for 6 consecutive days) injected intraperitoneally at doses of 50,100 or 300 mg/kg.Brain-derived neurotrophic factor (BDNF)protein (1 μg/side)or BDNF shRNA (2×10 5 units/side)was infused into the hippocampus.The behavioral changes in Y-maze,open field test and Morris water maze and the expression of BDNF in the hippocampus were analyzed. Results Acute treatment with curcumin had no significant effects on the spontaneous alteration,locomotor activity or water maze latency of AD rats.AD rats treated chronically with curcumin (300 mg/kg ) showed significant elevation in the spontaneous alternation (P <0.000 1)in Y-maze and memory ability in the water maze test (P <0.05 )compared with those in the saline group.Chronic treatment with 100 and 300 mg/kg of curcumin induced an increased level of BDNF in the hippocampus as compared with the saline controls (P <0.05 and <0.000 1). Intrahippocampal injection of BDNF significantly decreased the escape latency of AD rats in the water maze (F 4,2 9 5=5.813,P <0.01 ).Rats chronically injected with curcumin combined with shBDNF showed no difference in the swimming time in Ⅱ quadrant as compared with saline controls (P =0.657).However,rats in 100 mg/kg curcumin group,BDNF group and sham group had significantly increased swimming time than the saline controls (P <0.05, P <0.05 and P <0.000 1,respectively).Conclusion Curcumin may activate the downstream signaling pathways by upregulating the expression of BDNF and ultimately contribute to the improvement of learning and memory in AD rats.

Impulsive-like behaviors of rats in Y-maze task induced by pramipexole and its mechanism / 中国药理学与毒理学杂志

OBJECTIVE To analyze impulsive-like behaviors of SD rats induced by pramipexole in Y-maze avoidance tasks. METHODS Behaviors of SD rats in Y-maze avoidance tasks were recorded with a camera and analyzed by Noldus Etho Vision XT8 software after acute subcutaneous injection of pramipexole(0.1,1 and 10 mg · kg-1),including right reaction numbers of 20 consecutive avoidance tasks,shuttle number of times between the three arms of Y-maze, distance covered in Y-maze and time spent in safe arms during 20 consecutive avoidance tasks. Then,the prepulse inhibition(PPI)of the startle reflex test was used to assess the effect of pramipexole on sensorimotor gating (SG). Effects of pramipexole on the dialyzed content of monoamine neurotransmitter and its metabolites in the striatum and amygdala of SD rats were measured by microdialysis in vivo. RESULTS Compared with normal control group,the rats of pramipexole group showed a significant increase in the shuttle number of times and distance covered in Y-maze between Y-maze avoidance tasks(P<0.01),but a statistically significant decrease in the time spent in safe arms(P<0.01),while the number of right reactions in Y-maze avoidance tasks was not changed. Such premature responses were quite similar to certain impulsive-compulsive behaviors in rodent models,such as five-choice serial reaction time tasks. In the PPI test,pramipexole displayed an impairing effect on SG(P<0.01). The microdialysis results showed that there was an increase of dopamine and 5-hydroxytryptamine in the striatum of pramipexole group, but not statistically significant. Monoamine neurotransmitters and their metabolites were not significantly changed in the amygdala. CONCLUSION Pramipexole can induce impulsive-compulsive behaviors in Y-maze avoidance tasks,which might be attributed to impaired SG.

Crinum zeylanicum memory enhancing effect is mediated via central cholinergic transmission system.

Background: Crinum zeylanicum is widely used in the ethno-therapeutic management of folk management of epilepsy, pain, neuropsychiatric, and dementing disorders in Nigeria. The current study was carried out to evaluate the possible mechanism of the memory enhancing the effect of C. zeylanicum extract and alkaloidal rich fraction in Wistar rats. Methods: The effect of Crinum zeylanicum bulb extract (250, 500, and 1000 mg/kg body weight orally), alkaloidal rich fraction (10, 20, and 40 mg/kg body weight p.o.), normal saline (10 ml/kg orally), or Eserine (0.3 mg/kg body weight i.p.) on spatial memory in rats was evaluated using the Y-maze. The blood samples obtained from rats in all treatment groups were evaluated for cholinesterase activities using modified Michelle electrometric method. Results: The extract and the alkaloid significantly (p<0.05) and dose-dependently increased spontaneous alternation behavior of rats in Y-maze. The extract produced 20.00%, 35.55%, and 52.00% inhibition of cholinesterase activity in the blood at 250, 500, and 1000 mg/kg body weight, respectively. The alkaloid produced 56.67%, 62.67%, and 68.67% inhibition of cholinesterase activity in blood at 10, 20, and 40 mg/kg body weight (p.o.). Eserine a standard cholinesterase inhibitor at 0.3 mg/kg body weight produced a significant increase in spontaneous alternation behavior and produced 73.33% inhibition of blood cholinesterase activity. Data obtained from the study showed that the enhanced spontaneous alternation behavior observed in rats treated with the extract, and the alkaloid may be due to facilitation of cholinergic transmission resulting from inhibition of cholinesterase activity. Conclusion: The extract, as well as its partially purified alkaloid, possesses potential that may be employed for therapeutic management of Alzheimer’s disease.

Study on Neurobehavioral Disorders and NMDA Receptor Expression in Rats with Kidney-deficiency Constitution / 中国中医药信息杂志

ObjectiveTo discuss the correlation between kidney-deficiency constitution and brain function decline, and material basis of kidney-storing-spirit theory and neurobiology mechanism. Methods By employing the method of “cats scare rats”, composite offspring rat models with deficiency and acquired dystrophy were built, then they were divided into model group,ZuoguiPill group and Yougui Pill group. Blank group was composed from normal pregnant rats. When the intimidation of offspring began,Zuogui Pill andYougui Pill groups received gavage with corresponding doses of medicine, 1 times per day for 2 consecutive months. Model and blank groups received the same amount of normal saline. Exercise capacity was detected by suspension test. Learning and memory capacity was detected by Y maze test. Expressions of NMDA receptor subunits NR2A and NR2B were detected by immunohistochemical method.Results In suspension test, the duration of model group was shorter than blank group (P<0.05), while duration ofZuogui Pill andYougui Pill groups was longer than the model group (P<0.05). In Y maze test, the correct number of model group was less than blank group, and increased significantly after treatment (P<0.05). The optical density of NR2A and NR2B was lower in model group than blank group (P<0.05) and higher inZuogui Pill andYougui Pill groups than model group (P<0.05).ConclusionThe neurobehavioral is abnormal and NMDA receptor expression depresses in rats with kidney- deficiency constitution.ZuoguiPill andYouguiPill can rise NMDA receptor expression and improve brain function of rats, which reveal the correlation between kidney-deficiency constitution and brain function decline, and material basis of kidney-storing-spirit theory and neurobiology mechanism.

Administration of Phytoceramide Enhances Memory and Upregulates the Expression of pCREB and BDNF in Hippocampus of Mice

This study was aimed at investigating the possible effects of phytoceramide (Pcer) on learning and memory and their underlying mechanisms. Phytoceramide was orally administered to ICR mice for 7 days. Memory performances were assessed using the passive avoidance test and Y-maze task. The expressions of phosphorylated cAMP response element binding protein (pCREB), brain-derived neurotrophic factor (BDNF) were measured with immunoblot. The incorporation of 5-bromo-2-deoxyuridine (BrdU) in hippocampal regions was investigated by using immunohistochemical methods. Treatment of Pcer enhanced cognitive performances in the passive avoidance test and Y-maze task. Immunoblotting studies revealed that the phosphorylated CREB and BDNF were significantly increased on hippocampus in the Pcer-treated mice. Immunohistochemical studies showed that the number of immunopositive cells to BrdU was significantly increased in the hippocampal dentate gyrus regions after Pcer-treatment for 7 days. These results suggest that Pcer contribute to enhancing memory and BDNF expression and it could be secondary to the elevation of neurogenesis.

The long-term effects of physical exercise on recurrent neonatal seizure-induced cognitive deficit and ZnT3 expression in rat hippocampus / 中华物理医学与康复杂志

Institute of Pediatric,Suzhou University Affiliated Children's Hospital,Suzhou 215003,China Objective To explore the long-term effects of physical exercise on neonatal seizure-induced learning,memory deficit and the expression of zinc transporter-3(ZnT3)in rat hippocampus.Methods Sprague Dawlev rats aged 6 days were randomly divided into a recurrent-seizure group(RS)and a control group. At postnatal dav 6(P6),the recurrent seizures were induced by inhalation of the volatile agent flurothyl once a day for consecu tive 6 davs.The rats in the control group were placed in the container for an equal period of time as those in the RS group without exposure to flurothyl. Y-maze test was performed to evaluate learning and memory capacity at postnatal day 29 to 35 and 61 to 67,respectively.During the period of postnatal day 51 to 56,all the animals in the RS andcontrol groups were subject to a 30-minute daily aerobic exercise program for consecutive 6 days.All the animals weresacrificed at postnatal day 78,and the in situ hybridization method was used to detect the expression of ZnT3 mRNA in hippocampus. Results ①The number of trials needed for getting correct response to the electric stimulation in the first Y-maze test was(60±14.1)and(37.5±17.2)for the RS and control groups,respectively(P＜0.05),while that in the second Y-maze test carried out 24 hours later was(27.5±14.1)and(21±11.01)for the RS and the control groups,respectively(P＞0.05).②Memory test revealed no significant difference between the RS and thecontrol groups(P＞0.05).③In situ hybridization detection showed that the expression of ZnT3 mRNA in hippocam pus was not significantly different between the two groups.However,there showed a significant difference between the dentate gyrus and CA3 in the RS group with regard to the expression of ZnT3 mRNA(P＜0.05). Conclusions Physical exercise improves the learning capacity of neonatal seizure-induced cognitive deficit and might have effects on the regulation of zinc transporter gene expressions in hippocampus.

Effect of Status Epilepticus on Learning and Memory and Expression of Hippocampal Phosphorylated c-AMP Response Element Binding Protein in Developmental Rats / 实用儿科临床杂志

Objective To explore the effect of status epilepticus(SE) on learning and memory and expression of phosphorylated c-AMP response element binding protein(pCREB) in hippocampus in developmental rats.Methods Developmental male SD rats were assigned randomly to two groups:the SE rats,induced by intraperitoneal injection of pentylenetetrazole(PTZ);normal saline(NS) control group,received saline intraperitoneal.Learning and memory test with the Morris water maze and Y maze were performed at 7 days after SE.After testing,a subset of rats were killed and the brain was evaluated for pCREB immunostaining,an important transcription factor underlying learning and memory.Results In SE group,the mean escape latency of searching the platform significantly prolonged(P

Effects of 9-(4-Ethoxycarboxylyphenoxy)-6,7-dimethoxy-1,2,3,4-tetrahydro acridine on learning and memory ability in mice / 中国临床药理学与治疗学

AIM: To study the effects of 9 (4 Ethoxycarboxylyphenoxy) 6,7 dimethoxy 1,2,3,4 tetrahydro acridine (EDT) on learning and memory abilities. METHODS: The step down test and Y maze test were adopted in this study. RESULTS: EDT ( 2.5 , 5, 10 mg?kg -1 , ig? 5 d ) dose dependently improved the impairment of memory acquisition, memory consolidation and memory retrieval induced by scopolamine, NaNO 2 and alcohol in mice. CONCLUSION: EDT can improve learning and mermory ability in mice.

Promoting effects of beta-carotene from Dunaliella Salina on learning and memory in rats and mice / 中国海洋药物

The effects of ?-carotene from Dunaliella salina(?-C) at three doses(12.5,25 and 50 mg?kg~(-1),ip) on learning and memory in rats and mice were studied by using step-down test and Y-maze test.In step-down tests,?-C at all three tested doses had significant effects on normal mice,and could remarkably antagonize the memory impairment induced by scopolamine and 20 % alcohol,but could not antagonize the impairment induced by sodium nitrite.As the same result,?-C at three tested doses administration had significant effects on rats in Y-maze tests.These results suggested that ?-C as an antioxidant could improve the ability of learning and memory in rats and mice.