The correlation between the severity of hypoxic-ischemic brain damage in neonatal rats and subsequent abnormal neurobehavior / 中国新生儿科杂志

Objective:To assess the severity of hypoxic-ischemic brain damage (HIBD) in neonatal rats and predict the occurrence of subsequent neurobehavioral abnormalities after brain injury by scoring and magnetic resonance imaging (MRI).Methods:7-day-old of 60 Sprague-Dawley (SD) rats were randomly divided into control group (14 rats), sham operation group (14 rats) and HIBD model group (32 rats). HIBD model was established by right common carotid artery dissection with Rice-Vannucci method and hypoxia. Within 24 h after modeling, the rats in the model group were evaluated by general condition score and Longa score, and the surviving rats with moderate and severe HIBD were selected for the experiment. 24 h after modeling, 5 rats of the model group were randomly selected for 2,3,5-triphenyltetrazole chloride staining to verify cerebral infarction. 1 week after modeling, 6 rats from each group were randomly selected for hematoxylin-eosin staining to observe HIBD brain injury. 4 weeks after modeling, 4 rats were randomly selected from the control group and the sham operation group, and 8 rats from the remaining model group were used to evaluate the volume of brain damage by MRI. 5-6 weeks after modeling, the remaining 8 rats from each group were subjected to the Cylinder test, and at 13 weeks, they underwent the Morris water maze test to evaluate their neurobehavior.Results:In HIBD model group, 19 rats with moderate to severe HIBD were selected from 32 rats. 24 h after modeling, cerebral infarction was verified in all rats, indicating moderate to severe HIBD. Brain tissue pathology observed 1 week after modeling revealed predominantly gray matter brain damage. MRI showed that 7 out of 8 rats had moderate to severe HIBD. Compared to the control and sham operation groups, the model group exhibited a significant decrease in the usage rate of the left forelimb in the Cylinder test at 5-6 weeks after modeling ( P<0.05), and the latency period in Morris water maze test was significantly prolonged at 13 weeks after modeling ( P<0.05), and the times of crossing platform quadrant were significantly reduced ( P<0.05). There was no significant difference in the right brain injury volume between 24 h and 4 weeks model group ( P>0.05). The brain injury volume in model group was negatively correlated with the usage rate of left forelimb in cylinder test at 5-6 weeks and the times of crossing platform quadrant in Morris water maze test at 13 weeks ( P<0.05), and positively correlated with latency period in Morris water maze test at 13 weeks ( P<0.05). Conclusions:Within 24 h of HIBD modeling, the severity of brain injury can be preliminarily predicted by general condition score and Longa score. 4 weeks after modeling, in the chronic phase of brain injury, MRI was proved to be an excellent predictor for mid-term and long-term neurobehavioral abnormalities in HIBD rats.

Correlation between in-vivo mercury exposure from Cinnabaris and memory disorders in juvenile rat / 中国药科大学学报

@#Cinnabaris(α-HgS) is a mineral traditional Chinese material medica, as a tranquilizer and sedative, which is widely used in combination with herbs for the treatment of children high fever and convulsion.However, a large amount of mercury in Cinnabaris poses a potential risk to the immature central nervous system of children and probably causes severe memory disorders.Inthisstudy,three groups of juvenile rats were given low, medium, and high doses of Cinnabaris by oral gavage once a day for 14 continuous weeks, respectively.The blood mercury concentrations of the rats at different growth phases were monitored by atomic fluorescence spectrometry.The brain structural and functional changes related to the memory functions were investigated through HE staining and Morris water-maze test. Correlation analysis was conducted to clarify the dose- mercury exposure-toxic effect relationship of Cinnabaris and memory disorders.It was found thatthe blood mercury levels increased in both time- and dose-dependent manner.After the 14-week continuous administration of Cinnabaris, the pathological lesions in hippocampal neurons of rats in the high dose group were observed including pyknosis and disordered cell arrangement.In the Morris water-maze test, compared with the control group, rats in the high dose group exhibited the significantly prolonged latency to find the platform and the target quadrant, and the time spent in the target quadrant was obviously shortened. Thus, the significant correlations were established between Cinnabaris dose and mercury exposure,mercury exposure and memory disorders, respectively. In conclusion, the long-term and overdose administration of Cinnabaris in juvenile rats can increase the in-vivo mercury level, destroy the normal hippocampal morphological structure, and lead to memory disorders. This study provided scientific references for the potential mercury poisoning risks pharmacovigilance of Cinnabaris-containing paediatric formulations.

The role of electroacupuncture in regulating cell adhesion molecule L1 expression and in neuroprotection in Alzheimer′s disease / 中华物理医学与康复杂志

Objective:To observe any effect of electroacupuncture on the expression of L1 cell adhesion molecule (L1CAM) in mice modeling Alzheimer′s disease (AD) and also any effect on learning and memory.Methods:Thirty male APP/PS1 mice were randomly divided into a model group, an electroacupuncture (EA) group, and a no acupuncture (NA) group, each of 10. All the animals were modeled as AD. Ten C57BL/6 mice served as a control group. The mice in the EA and NA groups were given continuous 50Hz EA at a current intensity of 1mA at and near the Baihui (GV20) and Shenshu (BL23) acupoints, respectively, once a day for 14 days, while the other two groups were not given any EA. The mice in the model and control groups continued to be routinely fed without any special treatment such as electroacupuncture. After the intervention, any behavioral changes were evaluated by using a Morris Water Maze, and the expression of L1CAM, PTEN and p53 protein in the hippocampus of each group was detected using western blotting.Results:Compared with the control group, the escape latency in positioning navigation experiments was significantly longer in the model group on the first 5 days of Morris Water Maze testing. Compared with the model group, the escape latency was significantly shorter in the EA group on days 2 to 5 of the Morris Water Maze testing, and the expression of L1CAM had increased significantly in the electroacupuncture group compared with the model group while PTEN and p53 expression had decreased significantly. The average escape latency of the NA group was significantly longer than that of the model group on days 2 to 5 of the Morris Water Maze testing. The average L1CAM expression in the NA group had decreased significantly, and the expression of PTEN and p53 protein had increased significantly more than in the EA group. The escape latency was negatively correlated with L1CAM expression but positively correlated with p53 protein and PTEN expression.Conclusion:L1CAM is involved in learning and memory processes, at least in mice. Electroacupuncture can improve the learning and memory of mice modeling Alzheimer′s, which may be due to its promoting the expression of L1CAM and inhibiting the expression of PTEN and p53.

Vitamin D3 mediates spatial memory improvement through nitric oxide mechanism in demyelinated hippocampus of rat

Abstract Studies have revealed beneficial role of vitamin D3 in neuro-cognitive function. There is also supporting evidence on the involvement of nitric oxide (NO) in the neuro-protective action. However, its over production could contribute to brain disorders. In this study, demyelination was induced by ethidium bromide (EB) injection into the right side of the hippocampus area of male rats. Vitamin D3 was administered to rats for 7 and 28 days prior to behavioral experiments using Morris water maze (MWM). Travelled distance, time spent to reach the platform, and time spent in target zone, were considered for learning and spatial memory evaluation. Nitrite oxide (NO2-) concentration was measured as an indicator for nitric oxide production. The time spent to reach the platform and the travelled distance were decreased significantly by 28 days of vitamin D3 administration (compared to 7 days experiment). Time spent in target quadrant was significantly lowered by administered vitamin on day 28. Therefore, considering a number of studies that have shown the effect of vitamin D3 on cognition, these findings could support their potential effect. Besides, nitric oxide concentration significantly differed in 28 days of vitamin D3 treated group compared with the groups treated with EB or 7 days of vitamin D3.

Effect of Hei Xiaoyaosan on Neuroinflammation in AD Model Rats： Based on Wnt/β-catenin Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo explore whether Hei Xiaoyaosan can inhibit the inflammatory response in the hippocampi of Alzheimer's disease （AD） rats by regulating and activating the Wnt/β-catenin signaling pathway to improve the cognitive and memory dysfunction. MethodAmong the 90 male Wistar rats， 12 were randomly selected as the blank group （normal saline） and 12 as the sham operation group （normal saline）. For the remainder， amyloid β-protein42 （Aβ42） was injected in the left and right hippocampus to induce AD， and then the AD rats were randomized into model group， low-， medium-， and high-dose Hei Xiaoyaosan groups （corresponding doses of Hei Xiaoyaosan， ig）， and donepezil group （donepezil hydrochloride，ig）， with 12 in each group. The administration lasted 42 days. The pathological changes of hippocampal CA1 region was observed based on Nissl staining. The escape latency on the 1st to 5th day in Morris water maze was recorded and the spatial memory on the 6th day was tested. Enzyme-linked immunosorbent assay （ELISA） was employed to detect the expression of interleukin （IL）-6， IL-10， and tumor necrosis factor-α （TNF-α） in rat hippocampus and serum， Western blotting to examine the protein expression of glycogen synthase kinase-3β （GSK-3β）， β-catenin， and peroxisome proliferator-activated receptor gamma （PPARγ）， and real-time polymerase chain reaction （Real-time PCR） to determine the mRNA expression of rat GSK-3β， β-catenin， and PPARγ. ResultCompared with the blank group， the number of neurons in the hippocampal CA1 area of model group was significantly reduced， the arrangement was uneven， the cell body was damaged more obviously， and the Neisser body was unclear. The treatment group was significantly prolonged （P<0.01）， and the number of crossing stations was significantly reduced （P<0.01）， the levels of IL-10 in serum and hippocampus of rats in the model group were significantly decreased， while the levels of IL-6 and TNF-α were significantly increased （P<0.01）， the GSK-3β protein and mRNA in the model group were significantly increased， and the protein expressions of β-catenin and PPARγ were significantly decreased （P<0.01）， and the difference was more obvious. The number of neurons in the donepezil group was more distributed， neatly arranged， the structure was intact， and the Nissl bodies were clear and definite， the escape latency on the 3rd to 5th days in middle and high dose groups of Hei Xiaoyaosan and the donepezil group was significantly shortened （P<0.01）， the number of crossing platforms increased significantly （P<0.01）， the expression levels of IL-10 in the rat hippocampus and serum were significantly increased， while IL-6 and TNF-α were significantly decreased （P<0.01）， GSK-3β in the rat hippocampus was significantly increased. The expressions of GSK-3β protein and mRNA were significantly decreased， while the expression levels of β-catenin and PPARγ protein and mRNA were significantly increased （P<0.01）. There was no significant difference in each index between the donepezil hydrochloride group and the high-dose Hei Xiaoyaosan group. ConclusionHei Xiaoyaosan can inhibit the inflammatory response in the hippocampus of AD rats by regulating the Wnt/β-catenin signaling pathway， thereby alleviating the cognitive and memory impairment of AD rats.

Longshengzhi Capsules Improves Cognitive Function of Vascular Dementia Model Rats / 中国实验方剂学杂志

ObjectiveTo study the effect of Longshengzhi capsules on the cognitive function of vascular dementia （VD） rats and reveal the underlying mechanism. MethodA VD rat model was established by permanent ligation of bilateral common carotid arteries. The model rats were randomly assigned into the model group （normal saline for gavage）， Hydergine （0.54 mg·kg-1） group， and high-， medium-， and low-dose （2.16， 1.08， and 0.54 g·kg-1， respectively） Longshengzhi capsules groups， with 15 rats each group. Additionally， a sham group （normal saline for gavage） was designed in this study. Morris water maze test was conducted in the last week. Hematoxylin-eosin （HE） staining was employed for observation of the pathological changes in the hippocampal area of rat brain. Serum oxidative stress indicators including superoxide dismutase （SOD）， malondialdehyde （MDA）， and glutathione peroxidase （GSH-Px） were examined. The levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β） were determined by enzyme-linked immunosorbent assay （ELISA）. The expression levels of B cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， protein kinase B （Akt）， p-Akt， nuclear factor-κB （NF-κB）， intercellular cell adhesion molecule-1 （ICAM-1）， and matrix metallopeptidase-9 （MMP-9） were determined by Western blot. ResultMorris water maze results showed that compared with sham operation group， the escape latency of rats in model group was significantly prolonged， and the number of crossing platform was significantly reduced. Compared with model group， the time of escape latency in Longshengzhi capsules high- and medium-dose groups was significantly shortened， and the number of crossing platform was significantly increased. Compared with sham operation group， SOD and GSH-Px levels in model group were significantly decreased （P<0.05， P<0.01）， MDA levels were significantly increased （P<0.05）， TNF-α， IL-6 and IL-1β levels were significantly increased （P<0.01）. Compared with model group， the level of SOD in serum of Longshengzhi capsules high-dose group was significantly increased （P<0.05）， the level of GSH-Px in serum of Longshengzhi capsules high-， medium- and low-dose groups was significantly increased （P<0.05， P<0.01）， and the level of MDA was significantly decreased （P<0.05）. TNF-α， IL-6 and IL-1β levels were significantly decreased （P<0.05， P<0.01）. HE staining showed that Longshengzhi capsules could improve pathological damage in hippocampus of VD rats. Western blot results showed that compared with sham operation group， the protein expressions of Bax， NF-κB， MMP-9 and ICAM-1 in model group were significantly increased （P<0.01）， and the protein expressions of Bcl-2， Akt and p-Akt were significantly decreased （P<0.05， P<0.01）. The protein expression of Bax， NF-κB， MMP-9 and ICAM-1 in Longshengzhi capsules high-， medium- and low-dose groups was significantly decreased （P<0.05， P<0.01）， and the protein expression of Bcl-2 was significantly increased （P<0.05， P<0.01）. The protein expression of Akt in Longshengzhi capsules high- and medium-dose groups was significantly increased （P<0.05）. The expression of p-Akt protein in Longshengzhi capsules high-dose group was significantly increased （P<0.01）. ConclusionLongshengzhi capsules can improve the cognitive function of VD rats， and its mechanism may be related to the inhibition of oxidative stress， inflammatory response and apoptosis. ConclusionLongshengzhi capsules can improve the cognitive function of VD rats by inhibiting oxidative stress， inflammatory reaction， and neuronal apoptosis.

Octreotide-mediated neurofunctional recovery in rats following traumatic brain injury. Role of H2S, Nrf2 and TNF-α

ABSTRACT Purpose: To explore the role and mechanisms of octreotide in neurofunctional recovery in the traumatic brain injury (TBI) model. Methods: Rats were subjected to midline incision followed by TBI in the prefrontal cortex region. After 72 hours, the behavioural and neurological deficits tests were performed, which included memory testing on Morris water maze for 5 days. Octreotide (15 and 30 mg/kg i.p.) was administered 30 minutes before subjecting to TBI, and its administration was continued for three days. Results: In TBI-subjected rats, administration of octreotide restored on day 4 escape latency time (ELT) and increased the time spent in the target quadrant (TSTQ) on day 5, suggesting the improvement in learning and memory. It also increased the expression of H2S, Nrf2, and cystathionine-γ-lyase (CSE) in the prefrontal cortex, without any significant effect on cystathionine-β-synthase. Octreotide also decreased the TNF-α levels and neurological severity score. However, co-administration of CSE inhibitor (D,L-propargylglycine) abolished octreotide-mediated neurofunctional recovery, decreased the levels of H2S and Nrf2 and increased the levels of TNF-α. Conclusions: Octreotide improved the neurological functions in TBI-subjected rats, which may be due to up-regulation of H2S biosynthetic enzyme (CSE), levels of H2S and Nrf2 and down-regulation of neuroinflammation.

Serum amyloid A 3 deficiency improves cognitive impairment and attenuates tau pathology in mouse model of Alzheimer′s disease / 中国药科大学学报

@#To explore the effects of serum amyloid A (SAA) on the cognitive function and tau phosphorylation in Alzheimer''s disease (AD), two mouse models of AD were constructed: one is the APP/PS1 double transgenic mice mated with the Saa3 knockout (Saa3-/-) mice, and the other involves intracerebroventricular (ICV) injection of streptozotocin (STZ) into WT and Saa3-/- mice.The expression of Saa3 in mouse brain was evaluated using immunofluorescence staining.The body weight of STZ injection mice during modeling was measured.The motor coordination and balance, spontaneous exploratory activity, and anxiety level of these mice were assessed by Rotarod test, open field, and elevated plus maze, respectively.Spatial reference learning and memory were evaluated by Morris water maze.Western blot was used to detect the phosphorylation level of tau protein in mouse brain tissue.The results showed that the expression of Saa3 was increased in the brain of AD mice.The Saa3 gene deletion had no significant effect on motor coordination, balance and spontaneous exploratory activity in these mice, yet with alleviated anxiety level of AD model mice.Saa3 deficiency improved the impairment of learning and memory function of intracerebroventricular STZ injection mice and APP/PS1 mice. Deletion of Saa3 relieved the hyperphosphorylation of tau protein at specific sites in the brain of AD mice. The difference between the groups was statistically significant (P < 0.05). These results suggest that Saa3 is associated with cognitive function and tau pathology in AD, and that the inhibition of SAA may be a new strategy for the treatment of AD.

Neurotoxicity and hematotoxicity of maternal exposure to 1-bromopropane in male offspring rats / 中国职业医学

OBJECTIVE: To observe the neurotoxicity and hematotoxicity of maternal exposure to 1-bromopropane(1-BP) on the offspring rats by the breast-feeding route. Method A total of eight specific pathogen free female rats and their 64 male newborn rats were divided into the control group and the exposure group, with four lactation female rats and their 32 male newborn rats in each group. The female rats in exposure group were intragastrically administered with 700.00 mg/kg body mass of 1-BP during lactation, and the control group was given equal volume of corn oil for 21 days, once a day. The body mass of female rats and their offspring rats were measured during the exposure period. After exposure, the Morris water maze and the open field tests were performed in male offspring. The blood samples of offspring were collected for blood routine and blood biochemical indexes detection. The histopathological examination was performed in the hippocampus in the male offspring. RESULTS: A litter of eight pups in the exposure group began to die one day after the mother rat was exposed to 1-BP, and all rats died on the ninth day after exposure. There was no significant difference in the body mass of female rats between the exposure group and the control group(P>0.05). The body mass of offspring rats in the exposure group was lower than that in the control group at the same time point from the first day to the 21 st day of the female rats exposed to 1-BP(all P<0.05). In the orientation navigation experiment, the escape latency time on the first, the second day and the total distance on the first day in the offspring of the exposure group were significantly prolonged than those in the control group at the same time points(all P<0.05). The number of times of crossing the platform of offspring rats in the exposure group was less than that in the control group in the spatial exploration test(P<0.01). In the open field test, there was not statistical significance of the activity, rest time ratio, total distance, the distance ratio and time ratio in the central region in the offspring between the two groups(all P>0.05). The counts of white blood cells, neutrophils, lymphocytes, and average red blood cell width, platelet ratio and average platelet volume of the offspring of the exposure group decreased(all P<0.05), the serum levels of globulin, total protein, triacylglycerol and total bilirubin decreased(all P<0.05), and the albumin/globulin ratio and serum glucose level increased(all P<0.05), when compared with that of the control group. Histopathological examination results showed that the nerve fibers were loose in the hippocampal dentate gyrus area, and there were necrotic neurons and loss of nerve fibers in the CA1 area of the offspring rats. CONCLUSION: Maternal exposure to 1-BP during lactation can induce neurotoxicity and hematotoxicity to offspring rats. The neurotoxicity mainly caused damage to the central nerve system, which affected the learning and memory function of the offspring rats. The reason may be related to the damage caused by 1-BP on the hippocampal function.

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.

Phytochemical And Pharmacological Study Of Ashwagandha (withania Somnifera) Wild And Cultivated Varieties

Ashawagandha is herb used for various kinds of disease especially as a nervine tonic. Considering these facts many scientific studies were carried out and its memory, anti-stress activities were studied in detail. Aims and Objectives: To study the Phytochemical analysis and Pharmacological Study of Ashwagandha (Withania somnifera) varieties and Withania somnifera (L.) Dunal wild purified with milk steam (WSWM) root powder. To study the efficacy of Wild and Cultivated varieties of Ashwagandha on rats through Elevated Plus Maze test and Morris Water Maze (MWM) model. Materials and Methods: The formulations Withania somnifera (L.) Dunal wild (WSW) root powder, Withania somnifera (L.) Dunal Nagori (WSN) root powder, Withania somnifera (L.) Dunal wild purified with milk steam (WSWM) root powder, PG (Wheat powder placebo) were subjected to preliminary phytochemical screening for the detection of various chemical constituents present. Animal experimentation was done on Wistar Albino Rats obtained from the animal house attached and are divided into three groups consisting of 6 rats per group. Nootropic agents are effectively screened using this paradigm in scopolamine-induced dementia. Elevated Plus Maze and Morris Water Maze (MWM) model are based on this phenomenon. Results: By performing phytochemical analysis, Withania somnifera (L.) Dunal Nagori (WSN) showed the presence of alkaloids, carbohydrates, glycosides, phytosterols, saponins, proteins and amino acids. Withania somnifera (L.) Dunal wild purified with milk steam (WSWM) showed the presence of alkaloids, carbohydrates, glycosides, proteins and amino acids and wheat powder placebo (PG) showed the presence of alkaloids, carbohydrates, glycosides, saponins, phenolic compounds, tannins, proteins amino acids and flavonoids. Conclusion: The formulation group 3 (WSWM) showed remarkable reduction in the transfer latency time (in elevated plus maze test) from the acquisition day to the retention day and therefore considered Group 3 is statistically significant. The formulation group 3 (WSWM) showed remarkable reduction in the latency scores in Morris water maze and hence Group 3 (Ashwagandha wild purified with milk steam (WSWM) root powder) is statistically significant.

Sub-chronic manganese exposure leads to persistent damage of learning and memory ability in rats / 中国职业医学

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.

Efeitos do Estresse Crônico Moderado sobre o Desempenho de Ratos Wistar em Tarefas de Aprendizagem / Effects of Chronic Mild Stress on Performance of Wistar Rats in Learning Tasks

As pesquisas sobre o efeito do estresse crônico moderado (CMS) sobre a aprendizagem de não humanos apresentam resultados contraditórios. Este estudo investigou os efeitos do CMS sobre o desempenho de ratos em duas tarefas de aprendizagem: uma discriminação visual simultânea e uma aprendizagem espacial em labirinto aquático. Oito ratos Wistar machos foram divididos em grupo experimental (GE, exposto ao CMS) e grupo controle (GC). Após exposição do GE ao protocolo de CMS por três semanas, ambos os grupos passaram por uma tarefa de discriminação visual e pela tarefa de aprendizagem espacial no labirinto aquático de Morris (MWM), além de testes de preferência por solução de sacarose. O GE continuou sendo exposto ao CMS durante a tarefa de discriminação visual. Os resultados sugerem que o CMS pode ter reduzido o ganho de peso e dificultado a aprendizagem de discriminação visual do GE, sem alterações na preferência por sacarose e no MWM. De acordo com os resultados do presente estudo e da literatura em geral, os efeitos do CMS sobre a aprendizagem podem depender de sua duração e da complexidade da tarefa.

Researches on the effect of chronic mild stress (CMS) on non-human learning present contradictory results. This study investigated the effects of CMS on rats' performance in two learning tasks: a simultaneous visual discrimination and a spatial learning task in a water maze. Eight Wistar rats were divided into experimental group (GE, exposed to CMS) and control group (GC). After the GE group had been submitted to the CMS protocol for three weeks, both groups were exposed to a visual discrimination task and spatial learning task in the Morris Water Maze (MWM), in addition to preference tests for a sucrose solution. GE continued to be exposed to CMS for visual discrimination task. Results suggested that CMS may reduce weight gain and make the visual discrimination learning more difficult for the GE, without changes on the sucrose preference and MWM. According to the results of the present study and the literature in general, the effects of CMS on learning may depend on the duration and complexity of the task.

Efecto de la masticación sobre la memoria y aprendizaje espacial en ratones adultos y seniles / Effect of chewing on memory and spatial learning in adult and senile mice

Resumen Introducción: La masticación es una actividad periférica que influye positivamente sobre el sistema nervioso central (SNC). Sin embargo, a pesar de los diferentes estudios realizados, aún no está claro cómo la masticación afecta a los procesos cognitivos. Debido a ello se buscó determinar el efecto de la masticación sobre la memoria y aprendizaje espacial en ratones adultos y seniles. Materiales: Se empleó un grupo de 16 ratones adultos y de 16 ratones seniles que fueron aleatorizados en 2 subgrupos de 8 ratones cada uno. Un subgrupo se alimentó con dieta granosa convencional para ratón (subgrupo masticación normal), el otro subgrupo se alimentó con dieta en polvo (subgrupo masticación deficiente). Durante 2 meses se sometió a cada subgrupo a su dieta respectiva. Se evaluó en el laberinto acuático de Morris a los ratones adultos a los 7 meses de edad y a los seniles a los 12 meses de edad, mediante la fase de adquisición y de fase de recuperación de memoria y aprendizaje espacial. Resultados: Los ratones adultos, con masticación normal, mostraron mejor adquisición de memoria y aprendizaje espacial con respecto a los ratones con masticación deficiente en el primer día de evaluación (p = 0,035). Al agrupar a los ratones bajo el mismo tipo de masticación se encontró, en los subgrupos bajo masticación normal, una mejor adquisición de memoria y aprendizaje espacial en el subgrupo adulto sobre el subgrupo senil (p < 0,05). Conclusiones: La masticación normal tuvo un efecto positivo sobre la adquisición de información espacial en los ratones adultos.

Introduction: Chewing is a peripheral activity that positively influences the central nervous system (CNS). However, despite the different studies carried out, it is still not clear how chewing affects cognitive processes. Because of this, was trying to find the effect of chewing on memory and spatial learning in adult and senile mice. Methods: A group of 16 adult and senile mice were randomized into 2 subgroups of 8 mice each group. One subgroup was fed with conventional grainy diet for mice (normal chewing subgroup), the other subgroup was fed dietary powder (deficient chewing subgroup). During 2 months each subgroup was submitted to their respective diet. Adult mice at 7 months of age and senile at 12 months of age were evaluated in the Morris' water maze; through of the acquisition phase and the probe test of memory and spatial learning. Results: Adult mice with normal chewing showed better memory acquisition and spatial learning with respect to mice with deficient chewing on the first day of evaluation (p = 0.035). When grouping the mice in the same type of chewing, in the subgroups under normal chewing, a better acquisition of memory and spatial learning was found in the adult subgroup on than in the senile subgroup (p < 0.05). Conclusions: Normal chewing had a positive effect on the acquisition of spatial information in adult mice.

Effects of baicalin on cognitive function and expression levels of vascular endothelial growth factor and endostatin in cerebral small vessel disease model rats / 吉林大学学报(医学版)

Objective: To explore the effects of baicalin on the cognitive function and the expression of vascular endothelial growth factor (VEGF), and endostatin (ES) in the brain tissue of the cerebral small vessel disease model rats, and to clarify their mechanisms. Methods: The rat models of cerebellar small vessel disease were duplicated by in vitro implantation of allogeneic microemboli. After successfully modeling, 48 model rats were randomly divided into model group, low dose (50 mg · kg-1) of baicalin group, and high dose (100 mg · kg-1) of baicalin group (n=16); On and the sham operation rats were used as control group (n=16). On the first day after modeling, the rats in each group were given drugs, and the learning and memory function of the rats in various groups were detected by Morris water maze experiment at 7, 14, and 28 d after modeling, respectively. The expression levels of VEGF and ES mRNA and protein in the brain tissue of the rats in various groups were detected by RT-PCR and Western blotting methods, and the morphology of the hippocampus tissue of the brain of the rats in various groups were observed by HE staining; the expressions of VEGF and ES proteins in the hippocampus tissue of the brain of the rats in various groups were detected by immunohistochemistry. Results: Compared with control group, the escape latency in Morris water maze of the rats in model group was significantly prolonged (P<0. 01), the number of crossing the platform was significantly reduced (P<0. 01), the brain tissue lesion was severe, the expression levels of VEGF mRNA and protein in brain tissue were significantly decreased (P<0. 01), and the expression levels of ES mRNA and protein were significantly increased (P<0. 01). Compared with model group, the escape latency in Morris water maze of the rats in high dose of baicalin group was significantly shortened (P< 0. 01), the number of crossing the platform was significantly increased (P<0. 01), the degree of brain tissue lesion was alleviated, the expression levels of VEGF mRNA and protein in brain tissue were significantly increased (P< 0.01), and the expression levels of ES mRNA and protein were significantly decreased (P< 0.01). Conclusion: Baicalin can reduce the escape latency, improve the pathological changes, and repaire the cognitive function of brain tissue; it can decrease the VEGF expression level and increase the expression lvels of ES in the brain tissue of the cerebral small vessel disease model rats, and plays a protective role in the brain tissue.

Effect of total saponins of Panax notoginseng on learning and memory of global cerebral ischemia rats and its mechanism / 中草药

Objective: To explore the effect of the total saponins of Panax notoginseng (TSPN) on learning and memory of global cerebral ischemia rats and its mechanism. Methods: Using four-vessel occlusion method to establish the global cerebral ischemia model. Rats were divided into sham group, vehicle group, and TSPN group. The rats in the TSPN group were administered TSPN intraperitoneally 30 min post-brain ischemia. The dose of TSPN (75 mg/kg) was suspended in 0.9% saline 10 g/L, once per day for 14 d after reperfusion. Rats in the vehicle group were treated with equal volume of 0.9% saline, one injection per day for 14 d. The Morris Water Maze was performed to test the learning and memory of rats and doublecortin (DCX) and NeuN expression in the hippocampus was assessed by immunohistochemistry. Furthermore, immunoblotting was adopted to test the protein level of DCX in the CA1 subfield of hippocampus. Results: The escape latency in the vehicle group was longer than that in the TSPN group (P < 0.05). The times across the platform were less in the vehicle group than that in the TSPN group (P < 0.05). In comparison with the vehicle group, the number of the NeuN+ cells in the CA1 subfield and DCX+ cells in the SGZ of the TSPN group were significantly increased (P < 0.01); Moreover, the result of immunoblotting demonstrated that the protein level of DCX in the CA1 subfield of hippocampus of the TSPN group was significantly higher than that in the vehicle group (P < 0.01). Conclusion: TSPN could improve the learning and memory of global cerebral ischemia rats and its mechanism may be related to the promotion of hippocampus neurogenesis.

Effect of Shenghuitang on Learning Memory, Levels of IL-6, TNF-α and COX-2 in Hippocampus of Chronic Sleep Deprivation Mice / 中国实验方剂学杂志

Objective: To observe the effect of Shenghuitang on learning and memory and expressions of interleukin-6(IL-6), tumor necrosis factor-α(TNF-α) and cyclooxygenase-2(COX-2) in hippocampus of chronic sleep deprived mice, in order to explore the possible mechanism of Shenghuitang in improving learning and memory ability. Method: Mice were randomly divided into sleep deprivation group, blank group, melatonin group(7.8×10-4 g·kg-1·d-1), high, middle and low-dose Shenghuitang groups(54,27,13.5 g·kg-1·d-1). The model of chronic sleep deprivation in mice was established using the "multi-platform water environment method". 28 d sleep deprivation and intragastric administration were provided. Morris water maze was used to detect the learning and memory ability of mice in each group. Real time-PCR was used to detect mRNA expressions of IL-6, TNF-α and COX-2 in the hippocampus of each group. Result: The results of Morris water maze test showed that compared with the blank group, the total time spent on finding the platform and the total swimming distance of the model group were significantly prolonged (PPPPPPPPPα, and COX-2 were increased in the model group compared with the blank group. Compared with the model group, mRNA expressions of IL-6, TNF-α, and COX-2 were decreased in the treated group. COX-2 mRNA expression was down-regulated. Conclusion: Shenghuitang may improve the learning and memory ability of mice by decreasing mRNA expressions of IL-6, TNF-α and COX-2 in hippocampus.

Evaluating the impact of psoriasis on cognitive function in mouse models by using Morris water maze / 中华皮肤科杂志

Objective@#To evaluate the impact of psoriasis on spatial learning and memory abilities in mouse models by using Morris water maze.@*Methods@#Twenty healthy male C57BL/6J mice aged 10 months were randomly and equally divided into 2 groups: psoriasis group topically treated with imiquimod 5% cream on the back once a day for a week, and control group topically treated with vaseline once a day for a week. After successful establishment of mouse models, the Morris water maze (MWM) test was used to assess the learning and memory abilities in the mice in the 2 groups.@*Results@#In the place navigation experiment, the escape latency was significantly longer in the psoriasis group (38.24 ± 13.59 s) than in the control group (14.28 ± 3.80 s, t = 5.37, P < 0.01) . In the spatial probe test, the number of times passing through the platform (1.70 ± 0.95 vs. 5.00 ± 1.76, t = 5.21, P < 0.01) , the duration of stay in the target quadrant (t = 2.80, P < 0.05) and the swimming distance (t = 5.74, P < 0.01) were all significantly lower in the psoriasis group than in the control group. The psoriasis group showed significantly decreased swimming distance in the second quadrant (t = 2.49, P < 0.05) , but significantly longer duration of stay in the fourth quadrant compared with the control group (t = 2.46, P < 0.05) . There were no significant differences in swimming distance or duration of stay in other quadrants between the psoriasis group and control group (all P > 0.05) .@*Conclusion@#The spatial learning and memory abilities were impaired in the mouse model of psoriasis.

Establishment and evaluation of in vivo and in vitro D-galactose induced cognitive impairment models / 药学实践杂志

Objective To construct and explore the in vivo and in vitro D-galactose induced cognitive impairment models and evaluate the application value of the combined models in the study of cognitive impairments.Methods The cognitive impairment mice model induced by D-gal was prepared by continuous intraperitoneal injection of D-gal saline solution for 8weeks, followed by detection of learning and memory functions with Morris water maze.The related molecular markers in the brain tissue were assayed to evaluate the effect and application value.D-gal cell model was prepared by adding D-gal in different concentrations into the cell cultural medium of neurons harvested from the hippocampus of young mice.The effect and application value were evaluated by detecting the molecular markers related to the level of cell injury.Results The Morris water maze on the D-gal model showed that the learning and memory functions of mice in the model group were significantly lower than those in the control group.Meanwhile, the levels of apoptosis and oxidative stress in the model group were significantly higher than those in the control group.In the hippocampal neuron model of D-gal, the neurons showed a dose-dependent morphologic and functional change with the increase of D-gal dose and the levels of apoptosis and oxidative stress were significantly higher than those in the negative control.Conclusion D-galactose can be successfully used to induce cognitive impairment models both in vivo and in vitro through the decrease of the learning and memory functions of mice and induction of apoptosis and oxidative stress in neurons.Combined application of the two models of D-gal can be one of effective and promising tools for the study of cognitive impairment and pharmacodynamic evaluation.

The effect of moderate running wheel exercise on the learning and memory ability and hippocampal neurogenesis in young mice / 中华行为医学与脑科学杂志

Objective To observe the effect of moderate running wheel exercise on the learning and memory ability and hippocampal neurogenesis in young mice.Methods Twenty male 1 month old Kunming mice were randomly divided into control group and exercise group.After 8 weeks of running wheel exercise in the exercise group,the Morris water maze test was used to detect the spatial learning and memory ability of the two groups of mice.Immunohistochemical technique was used to detect the expression of Sox2,Ki67 and DCX in the dentate gyrus of mice in two groups,and those specific protein can reflected the hippocampal neurogenesis.Results In the place navigation test of Morris water maze,the latency of the exercise group ((29.00± 1.32) s) was lower than that of the control group ((36.30±0.69) s),and the difference was statistically significant (t=5.154,P＜0.05).In the spatial probe test,the number of times of crossing platforms in the exercise group ((3.73±1.51) times) was more than that of the control group ((1.89±t 1.63) times),and the difference was significant (t=3.583,P＜0.05).Immunohistochemical results showed that the number of Sox2,Ki67 and DCX immunoreactive cells in the dentate gyrus region of the exercise group were ((284.40± 31.50),(54.50± 10.75),(77.80=t± 11.60) respectively) more than those in the control group ((241.40± 10.57),(37.00± 7.81),(48.20±t 11.86) respectively),and the difference was statistically significant (t =4.129,5.789,7.971,all P＜0.01).Conclusion Moderate running wheel exercise can significantly improve the learning and memory ability of young mice,which may be related to the promotion of neurogenesis in the dentate gyrus of the hippocampus.