Efecto del estímulo masticatorio y estrés agudo sobre la interleuquina 6, la memoria y el aprendizaje espacial en ratones Balb/c

Introducción. El estrés agudo altera la memoria y aprendizaje espacial y la expresión de la interleuquina 6 (IL-6), mientras que el estímulo masticatorio evitaría dichos efectos. Objetivo. Determinar el efecto del estímulo masticatorio y el estrés agudo sobre la expresión de interleuquina 6, la memoria y el aprendizaje espacial en ratones. Métodos. Experimento con 70 ratones albinos machos de 2 meses de edad de la cepa Balb/c que fueron distribuidos aleatoriamente en grupo A1: estrés agudo 1 hora; grupo A2: estrés agudo 1 hora + estímulo masticatorio 1 hora; grupo B1: estrés agudo 2 horas; grupo B2: estrés agudo 2 horas + estímulo masticatorio 2 horas; grupo C1: estrés agudo 3 horas; grupo C2: estrés agudo 3 horas + estímulo masticatorio 3 horas; y grupo D: sin intervención. Durante 3 días, se evaluó la memoria y el aprendizaje espacial en el laberinto acuático de Morris. La IL-6 fue determinada mediante ELISA. Resultados. La IL-6 fue mayor en el grupo B2 vs los demás grupos (p < 0,001). Además, en el primer día de evaluación, la adquisición de memoria y aprendizaje espacial fue menor en el grupo A1 vs A2 (p = 0,042). Conclusión. Solo en el primer día de evaluación encontramos que el estímulo masticatorio previno la disminución de la adquisición de memoria y aprendizaje espacial en ratones sometidos a estrés agudo de baja intensidad. Los resultados en general no fueron concluyentes sobre el efecto del estímulo masticatorio. Además, la IL-6 fue mayor en el estrés + el estímulo masticatorio (grupo B2) sobre el resto.

Introduction. Acute stress alters memory and spatial learning and the expression of interleukin 6, the chewing stimulus would prevent these effects. Objective. To determine the effect of chewing stimulation and acute stress on the expression of interleukin 6 and memory and spatial learning in mice. Methods. Experiment where 70 male albino mice of the Balb/c of age 2 month were randomly distributed into: Group A1: acute stress 1 hour; Group A2: acute stress 1 hour + chewing stimulus 1 hour; Group B1: acute stress 2 hours; Group B2: acute stress 2 hours + chewing stimulus 2 hours; Group C1: acute stress 3 hours; C2: acute stress 3 hours + chewing stimulus 3 hours; Group D: without intervention. For 3 days, spatial memory and learning were tested in the Morris water maze. Interleukin 6 (IL-6) was analyzed by ELISA test. Results. IL-6 was higher in the B2 group vs the other groups (p<0.0001). In addition, on the first day of evaluation, the acquisition of spatial memory and spatial was lower in the A1 vs. A2 group (p=0.042). Conclusión. Only on the first day of evaluation, we found that the masticatory stimulus prevented the decrease in memory acquisition and spatial learning in mice subjected to low-intensity acute stress. The results were generally inconclusive on the effect of masticatory stimulation. In addition, IL-6 was higher in the stress + masticatory stimulus (group B2) over the rest.

Effects of subchronic exposure to benzoɑpyrene on memory function and mRNA expressions of NMDA receptors in different brain regions in rats / 环境与职业医学

Background The altered expressions of hippocampal N-methyl-D-aspartate (NMDA) receptors induced by benzo[ɑ]pyrene (BaP) causes short-term spatial learning and memory impairment in humans and animals, but whether BaP causes alterations of NMDA receptor subunits in other brain regions and the associated neurotoxic mechanism is still essentially unknown. Objective To observe the mRNA expressions of NR1, NR2A, and NR2B of NMDA receptor subunits in different brain regions in SD rat model with subchronic exposure to BaP, and to provide a basis for in-depth study of the mechanism of BaP-induced neurotoxicity. Methods Forty male SD rats were selected and randomly divided into a control group and 1.00, 2.50, and 6.25 mg·kg−1 BaP exposure groups with 10 rats in each group. The exposure rats received intraperitoneal injection of BaP every other day for 90 d.The average latency to platform, the average total distance, and the duration spent in previous quadrant were measured by the Morris Water Maze. Real-time fluorescence quantitative PCR was used to detect the mRNA expressions of NR1, NR2A, and NR2B in hippocampus, cortex, cerebellum, and striatum of rats. Results The average latency to platform and the average total distance in the 2.50 and 6.25 mg·kg−1 BaP groups were significantly prolonged compared with the control group (P<0.05), and the duration that rats spent in previous quadrant in the 6.25 mg·kg−1 BaP group was significantly shortened (P<0.05). Compared with the control group, the mRNA expressions of NR1 and NR2B in the hippocampus in the 2.50 and 6.25 mg·kg−1 BaP groups were significantly reduced (P<0.05), and the NR2A mRNA expression in the hippocampus in the 6.25 mg·kg−1 BaP group was significantly reduced (P<0.05); the mRNA expressions of NR1 and NR2B in the cortical tissue in the 6.25 mg·kg−1 BaP group were significantly reduced (P<0.05), and the mRNA expression of NR2A in the cortical tissue in the 1.00 mg·kg−1 BaP group was reduced; the mRNA expression of NR2B in the cerebellar tissue in the 6.25 mg·kg−1 BaP group was significantly reduced (P<0.05); there were no differences in the mRNA expressions of NMDA receptor subunits in the striatum tissue (P>0.05). Conclusion Subchronic BaP exposure can cause short-term spatial learning and memory impairment in rats, which may be related to the down-regulation of mRNA expressions of NR1, NR2A, and NR2B in hippocampus, changes of mRNA expressions of NR1, NR2A, and NR2B in cortical area, and the down-regulation of NR2B mRNA expression in cerebellum.

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.

Análisis de tareas para las funciones espaciales en niños escolares con diagnóstico de TDAH / Analysis of Tasks Used for Assessment of Spatial Function in Schoolchildren with ADHD / Análise de tarefas para as funções espaciais em crianças escolares com diagnóstico de TDAH

Resumen Objetivo. Identificar y precisar las dificultades en funciones espaciales que presentan los niños con TDAH en edad escolar. Método. Se evaluaron 24 niños, entre los 6 y los 12 años de edad, con diagnóstico de TDAH. Todos los niños fueron evaluados con tareas gráficas, tareas verbales y tareas constructivas, incluidas en las pruebas Evaluación Neuropsicológica Infantil, Evaluación Neuropsicológica de la Integración Espacial y Evaluación Neuropsicológica del Éxito Escolar. Resultados. El análisis clínico realizado al desempeño de los niños mostró dificultades no solo en el manejo de la proporción, la integración y al dibujar ángulos, sino en el uso adecuado del espacio e inversión. Las dificultades espaciales estuvieron acompañadas de otras de índole regulatorio, tono de activación, motoras y cinestésicas. Los participantes con mayor número de errores fueron aquellos de menor edad. Conclusión. Los niños con diagnóstico de TDAH pueden presentar dificultades en el desarrollo de las funciones espaciales, por lo cual se hace necesario que la evaluación neuropsicológica incluya un análisis profundo de esta dimensión cognitiva, que permita indagar la naturaleza de estas dificultades y su posible relación con el desarrollo de otras funciones.

Abstract Objective. Identify and detail the difficulties in children with attention deficit disorder in spatial function tasks. Method. 24 school children between 6 and 12 years old with diagnosis of attention deficit disorder were included in the study. Neuropsychological tasks used in the study were divided in graphic tasks, verbal tasks and a constructive task, all of them included in the Neuropsychological Evaluation for Children, Neuropsychological Evaluation of the Spatial Integration and Neuropsychological Evaluation of School Success assessments. Results. Analysis of the results has pointed out specific errors in graphic tasks such as disproportion, disintegration, difficulties with angles, problems with usage of space and inversions. Younger participants with complex neuropsychological syndromes committed more mistakes. The spatial difficulties were accompanied by regulatory, activation, motor and kinesthetic difficulties. The participants with higher frequencies of error were those of lower age. Conclusion. The results show that children with attention deficit disorder diagnosis may have difficulties in the development of spatial function; therefore, it is necessary to include a more profound neuropsychological analysis of the domain that allows the investigation of the nature of the difficulties and its plausible relation to the development of other functions.

Resumo Escopo. Identificar e reconhecer as dificuldades em funções espaciais que apresentam as crianças com TDAH em idade escolar. Metodologia. Foram avaliadas 20 crianças masculinas e 4 femininas, com idades compreendidas entre os 6 e 12 anos de idade, com diagnóstico de TDAH. Todas as crianças foram avaliadas com tarefas gráficas, tarefas verbais e tarefas construtivas, incluídas nas provas Avaliação Neuropsicológica da Integração espacial e Avaliação Neuropsicológica do Sucesso Escolar. Resultados. A análise clínica realizada aos desempenhos das crianças, mostraram dificuldades de desproporção, desintegração, dificuldade para desenhar ângulos, uso inadequado do espaço e inversão. As dificuldades espaciais estiveram acompanhadas de outras de natureza regulatória, tono de ativação, motoras e cinestésicas. Os participantes com maior número de erros foram aqueles de menor idade. Conclusão. As crianças com diagnóstico de déficit de atenção podem apresentar dificuldades no desenvolvimento das funções espaciais, pelo qual é preciso que a avaliação neuropsicológica possa incluir uma análise profunda de esta dimensão cognitiva, que permita indagar a natureza de estas dificuldades e sua possível relação com o desenvolvimento de outras funções.

Effects of different doses of methamphetamine on spatial learning and memory in mice and the mechanism / 西安交通大学学报(医学版)

Objective: To investigate the different-dose effects of methamphetamine (METH) on spatial learning and memory and the possible mechanisms. Methods: C57BL/6 mice were treated with 0.5, 1.0 and 2.0 mg/kg of METH or normal saline. The drug was injected intraperitoneally 30 min prior to the Morris water maze. All mice experienced 5 consecutive days' positioning navigation experiment and the spatial exploration experiment conducted 24 hours after the last training trial. Immediately after the probe test, the mice were killed by cervical dislocation and the hippocampus was dissected. Western blot was used to detect changes in phosphorylation levels of extracellular signal-regulated kinase (ERK1/2) and cAMP response element-binding protein (CREB) in the hippocampus. Results: Compared with the mice in saline group, those in 1.0 mg/kg METH group had a significantly shorter latency (P<0.05), spent more time in the target quadrant (P<0.05), and had more platform site crossings (P<0.05). Moreover, 0.5 and 2.0 mg/kg of METH did not significantly affect the mice's spatial learning and memory, but 0.5 mg/kg of METH showed a memory-promoting trend, while 2.0 mg/kg of METH showed a memory-destroying trend. METH of 1.0 mg/kg significantly increased p-ERK1/2 (P<0.05) and p-CREB (P<0.05) levels in the hippocampus. Conclusion: METH of 1.0 mg/kg significantly improved mice's spatial learning and memory. The effect of METH is an inverted U-curve among three doses of METH at 0.5, 1.0 and 2.0 mg/kg. ERK1/2 and CREB in the hippocampus may be involved in METH-induced improvement of spatial learning and memory in mice.

Expression of neuronal migration-related factors and the spatial learning and memory of rats prenatally exposed to tritiated water / 中华放射医学与防护杂志

Objective To study the expression of neuronal migration-related factors and spatial learning and memory of rats exposed to tritiated water (HTO).Methods Hippocampal neural cells from newborn Sprague-Dawley (SD) rats at postnatal 24 h were primarily cultured in DMEM/F12 medium with 20％ of fetal bovine serum for 6 days,followed by subjection to tritiated water (HTO) at concentrations of 3.7× 102,3.7×103,3.7 × 104,3.7 × 105,3.7× 106 Bq/ml for 24 h,respectively.Western blot and RT-qPCR were used to determine the expression levels of F-actin,α-tubulin,tau,AP2,BDNF mRNA and Reelin mRNA.16 pregnant SD rats at embryonic (E) day 14 were randomly divided into the tested and control groups (8 rats/ each group).The tested rats were injected with body fluid of HTO (3.7× 106 Bq/g) intraperitoneally,while the saline as the control.Morris water maze (MWM) was employed for the spatial learning and memory of rats.Results Compared to the control cells,HTO caused a significant downregulation of expressions of cytoskeletal proteins [F-actin (t =8.898-19.896,P＜ 0.05),α-tubulin (t=3.261-7.900,P＜0.05),tau (t=2.274-5.003,P＜0.05),and MAP2 (t=2.274-5.003,P＜0.05)] and mRNA of BDNF (t=3.580-19.792,P＜0.05) and Reelin (t=3.240-39.692,P＜0.05)in the tested neural cells in a dose-dependent manner.In addition,the escape latency of irradiated offsprings was significantly prolonged (t =-2.563,P＜0.05),the time for offsprings to cross through target quadrant was markedly reduced (t=3.214,P＜0.05),and the swimming time in the platform quadrant of irradiated offsprings were obviously shortened (t =3.874,P＜0.05) in the MWM trial.Conclusions The results indicate that HTO irradiation in utero downregulates the expressions of neuron migration-related factors and induces brain dysfunction,which may shed a light on a mechanism of the radiation-induced brain impairment.

Expression of neuronal migration-related factors and the spatial learning and memory of rats prenatally exposed to tritiated water / 中华放射医学与防护杂志

Objective@#To study the expression of neuronal migration-related factors and spatial learning and memory of rats exposed to tritiated water (HTO).@*Methods@#Hippocampal neural cells from newborn Sprague-Dawley(SD) rats at postnatal 24 h were primarily cultured in DMEM/F12 medium with 20% of fetal bovine serum for 6 days, followed by subjection to tritiated water(HTO) at concentrations of 3.7×102, 3.7×103, 3.7×104, 3.7×105, 3.7×106 Bq/ml for 24 h, respectively. Western blot and RT-qPCR were used to determine the expression levels of F-actin, α-tubulin, tau, AP2, BDNF mRNA and Reelin mRNA. 16 pregnant SD rats at embryonic (E) day 14 were randomly divided into the tested and control groups (8 rats/ each group). The tested rats were injected with body fluid of HTO (3.7×106 Bq/g) intraperitoneally, while the saline as the control. Morris water maze (MWM) was employed for the spatial learning and memory of rats.@*Results@#Compared to the control cells, HTO caused a significant downregulation of expressions of cytoskeletal proteins [F-actin (t=8.898-19.896, P<0.05), α-tubulin (t=3.261-7.900, P<0.05), tau (t=2.274-5.003, P<0.05), and MAP2 (t=2.274-5.003, P<0.05)] and mRNA of BDNF(t=3.580-19.792, P<0.05) and Reelin (t=3.240-39.692, P<0.05) in the tested neural cells in a dose-dependent manner. In addition, the escape latency of irradiated offsprings was significantly prolonged (t=-2.563, P<0.05), the time for offsprings to cross through target quadrant was markedly reduced (t=3.214, P<0.05), and the swimming time in the platform quadrant of irradiated offsprings were obviously shortened (t=3.874, P<0.05) in the MWM trial.@*Conclusions@#The results indicate that HTO irradiation in utero downregulates the expressions of neuron migration-related factors and induces brain dysfunction, which may shed a light on a mechanism of the radiation-induced brain impairment.

Comparative Study of ROCK1 and ROCK2 in Hippocampal Spine Formation and Synaptic Function / 神经科学通报·英文版

Rho-associated kinases (ROCKs) are serine-threonine protein kinases that act downstream of small Rho GTPases to regulate the dynamics of the actin cytoskeleton. Two ROCK isoforms (ROCK1 and ROCK2) are expressed in the mammalian central nervous system. Although ROCK activity has been implicated in synapse formation, whether the distinct ROCK isoforms have different roles in synapse formation and function in vivo is not clear. Here, we used a genetic approach to address this long-standing question. Both Rock1 and Rock2 mice had impaired glutamatergic transmission, reduced spine density, and fewer excitatory synapses in hippocampal CA1 pyramidal neurons. In addition, both Rock1 and Rock2 mice showed deficits in long-term potentiation at hippocampal CA1 synapses and were impaired in spatial learning and memory based on the water maze and contextual fear conditioning tests. However, the spine morphology of CA1 pyramidal neurons was altered only in Rock2 but not Rock1 mice. In this study we compared the roles of ROCK1 and ROCK2 in synapse formation and function in vivo for the first time. Our results provide a better understanding of the functions of distinct ROCK isoforms in synapse formation and function.

Egocentric and allocentric spatial memory in healthy aging: performance on real-world tasks

Although normal aging has been related to several cognitive difficulties, other processes have been studied less, such as spatial memory. Our aim was to compare egocentric and allocentric memory in an elderly population using ecological tasks. Twenty-eight cognitively unimpaired participants performed Egocentric and Allocentric Spatial Memory Tasks, as well as Spatial Span from CANTAB, Benton's Judge of Line Orientation test (JoLO), and Montreal Cognitive Assessment test (MoCA). The results revealed that younger participants showed better performance than older participants on both the Egocentric and Allocentric Spatial Memory Tasks, although only the Egocentric test was able to discriminate between younger, middle, and older elderly participants. Learning effect was found in Allocentric Spatial Memory Task in younger and older groups, but not in the middle group. Allocentric and egocentric performance was not related to other visuospatial neuropsychological scores and gender did not influence performance in any task. Egocentric and Allocentric Spatial Memory Tasks may be useful tools in early screening for cognitive decline, as they are able to detect age differences in the cognitive unimpaired elderly population.

Small-scale environmental enrichment and exercise enhance learning and spatial memory of Carassius auratus, and increase cell proliferation in the telencephalon: an exploratory study

Carassius auratus is a teleost fish that has been largely used in behavioral studies. However, little is known about potential environmental influences on its performance of learning and memory tasks. Here, we investigated this question in C. auratus, and searched for potential correlation between exercise and visuospatial enrichment with the total number of telencephalic glia and neurons. To that end, males and females were housed for 183 days in either an enriched (EE) or impoverished environment (IE) aquarium. EE contained toys, natural plants, and a 12-hour/day water stream for voluntary exercise, whereas the IE had none of the above. A third plus-maze aquarium was used for spatial and object recognition tests. Different visual clues in 2 of its 4 arms were used to guide fish to reach the criteria to complete the task. The test consisted of 30 sessions and was concluded when each animal performed three consecutive correct choices or seven alternated, each ten trials. Learning rates revealed significant differences between EE and IE fish. The optical fractionator was used to estimate the total number of telencephalic cells that were stained with cresyl violet. On average, the total number of cells in the subjects from EE was higher than those from subjects maintained in IE (P=0.0202). We suggest that environmental enrichment significantly influenced goldfish spatial learning and memory abilities, and this may be associated with an increase in the total number of telencephalic cells.

Effects of chronic restraint stress on abilities of spatial learning and memory and levels of excitatory amino acids in hippocampal dentate gyrus in old rats / 吉林大学学报(医学版)

Objective: To explore the effects of chronic restraint stress (CRS) on the abilities of spatial learning and memory and the levels of excitatory amino acids in the hippocampal dentate gyrus (DG) in the old rats, and to investigate the neurochemical mechanism of CRS in affecting the spatial learning and memory abilities. Methods: Sixteen male SD rats (18 months old) were randomly divided into control group (n=8) and CRS group (n=8), and the rats in CRS group received CRS 2 h every day for 30 d. And then the spatial learning and memory abilities of rats were measured by Morris water maze (MWM) test, and the extracellular levels of excitatory amino acids including asparate (Asp) and glutamate (Glu) in the DG were simultaneously determined by in vivo microdialysis and HPLC. The levels of corticosterone (CORT) and epinephrine (EPI) in serum of the rats were examined by ELISA assay. Results: In CRS group, the escape latencies on the 2nd-4th days were significantly increased and the percentage of time spent in target quadrant on the 5th day was markedly decreased in MWM test compared with control group (P0. 05). Compared with control group, the levels of CORT and EPI in the serum of the rats in CRS group were significantly increased (P<0. 05). Conclusion: CRS impairs the spatial learning and memory abilities in the old rats, which may be related to the decrease of Asp level in the hippicampal DG of the rats.

Comparison of the cognitive function in rats at different brain developmental stages / 中国实验动物学报

Objective To investigate the relationship between different brain developmental stages and changes of cognitive function in rats. Methods 1-month, 2-month and 8-month-old rats were selected to imitate the juvenile, adolescent and adulthood, respectively, and their behavioral functions were compared. The reward operant conditioning and Morris water maze task were used to investigate the differences in exploration interest, executive and recognition ability, spatial learning and memory of the rats at different ages. Results In the reward operant conditioning and Morris water maze task, there was no significant difference in the cognitive function between 1-month and 2-month-old rats. In the reward conditioning phase, the nose pokes numbers of 8-month-old rats were significantly decreased compared with the 1-month-old rats (P＜ 0. 01). There was no significant difference in nose pokes accuracy. During the operant conditioning phase, the lever press numbers and accuracy of 8-month-old rats were significantly decreased ( P ＜ 0. 05 or P ＜ 0. 01) and the press latency was longer (P ＜ 0. 05). At the phase of visual identification, the press and reward numbers, and the visual identification index were significantly decreased ( P ＜ 0. 05 or P ＜ 0. 01). In the Morris water maze test, compared with the 1-month-old rats, the total swimming distance and escape latency of the 8-month-old rats were significantly increased (P＜ 0. 05), as well as average swimming speed ( P ＜ 0. 05 or P ＜ 0. 01) in spatial learning phage. In spatial memory phage, the swimming distance and time spent in the target quadrant were obviously decreased (P＜ 0. 01). Conclusions The cognitive functions of rats at different brain developmental stages are different. The juvenile and adolescent rats have similar cognitive functions, but 8-month-old adult rats appear decline in the exploration interest, executive and recognition ability, and spatial learning and memory function.

Spatial Learning and Memory Using a Radial Arm Maze with a Head-Mounted Display

OBJECTIVE: A radial arm maze (RAM) is an essential tool for assessing spatial learning and memory. Although this tool is widely used to study deficits in spatial memory in animal models, it has several restrictions that prevent its adaptation to human research and training. Therefore, we developed a head-mounted-display RAM (HMD-RAM) program for humans and verified its validity by comparing it to the results obtained by previous RAM studies. We also compared the HMD and a flat monitor as experimental devices. METHODS: Forty participants were recruited for the current study (Study 1: 20 participants with the HMD device; Study 2: 20 participants with the flat monitor). They navigated a virtual room as a first-person viewer and used environmental landmarks to remember their spatial position and orientation. The main dependent measures were working memory error, reference memory error, detection time, travel distance, and participant’s head movements. To validate the program, participants also conducted neuropsychological assessments and self-reported measures. RESULTS: The results for HMD-RAM tasks were consistent with the results of previous research conducted on animals, and the HMD elicited a higher sense of presence, immersion, and simulator sickness than the flat monitor. According to post-experiment questions on navigation strategy, creating landmarks was important when people were discovering locations in their environment, and an HMD was beneficial for better navigation strategy. CONCLUSION: These results suggest that the HMD-RAM is valuable for estimating spatial learning and memory in humans and may be a useful tool for early diagnosis of deficits in spatial learning and memory, including amnestic mild cognitive impairment and Alzheimer’s disease.

Effects of chronic restraint stress on abilities of spatial learning and memory and levels of excitatory amino acids in hippocampal dentate gyrus in old rats / 吉林大学学报(医学版)

Objective:To explore the effects of chronic restraint stress (CRS) on the abilities of spatial learning and memory and the levels of excitatory amino acids in the hippocampal dentate gyrus (DG) in the old rats,and to investigate the neurochemical mechanism of CRS in affecting the spatial learning and memory abilities.Methods:Sixteen male SD rats (18 months old) were randomly divided into control group (n =8) and CRS group (n=8),and the rats in CRS group received CRS 2 h every day for 30 d.And then the spatial learning and memory abilities of rats were measured by Morris water maze (MWM) test,and the extracellular levels of excitatory amino acids including asparate (Asp) and glutamate (Glu) in the DG were simultaneously determined by in vivo microdialysis and HPLC.The levels of corticosterone (CORT) and epinephrine (EPI) in serum of the rats wereexamined by ELISA assay.Results:In CRS group,the escape latencies on the 2nd-4th days were significantly increased and the percentage of time spent in target quadrant on the 5th day was markedly decreased in MWM test compared with control group (P＜0.05).Compared with before training,the extracelluar level of Asp in the DG in control group was significantly increased on the 2nd day in MWM test;compared with control group,the extracelluar level of Asp in the DG in CRS group was significantly decreased on the 3rd day in MWM test (P＜0.05).Compared with before training,the Glu levels in the DG in MWM test in both control and CRS groups were markedly increased (P＜0.05),but there was no significant difference between two groups (P＞0.05).Compared with control group,the levels of CORT and EPI in the serum of the rats in CRS group were significantly increased (P＜0.05).Conclusion:CRS impairs the spatial learning and memory abilities in the old rats,which may be related to the decrease of Asp level in the hippicampal DG of the rats.

Identification of Vestibular Organ Originated Information on Spatial Memory in Mice / 대한평형의학회지

OBJECTIVES: We aimed to study the role of vestibular input on spatial memory performance in mice that had undergone bilateral surgical labyrinthectomy, semicircular canal (SCC) occlusion and 4G hypergravity exposure. METHODS: Twelve to 16 weeks old ICR mice (n=30) were used for the experiment. The experimental group divided into 3 groups. One group had undergone bilateral chemical labyrinthectomy, and the other group had performed SCC occlusion surgery, and the last group was exposed to 4G hypergravity for 2 weeks. The movement of mice was recorded using camera in Y maze which had 3 radial arms (35 cm long, 7 cm high, 10 cm wide). We counted the number of visiting arms and analyzed the information of arm selection using program we developed before and after procedure. RESULTS: The bilateral labyrinthectomy group which semicircular canal and otolithic function was impaired showed low behavioral performance and spacial memory. The semicircular canal occlusion with CO₂ laser group which only semicircular canal function was impaired showed no difference in performance activity and spatial memory. However the hypergravity exposure group in which only otolithic function impaired showed spatial memory function was affected but the behavioral performance was spared. The impairment of spatial memory recovered after a few days after exposure in hypergravity group. CONCLUSIONS: This spatial memory function was affected by bilateral vestibular loss. Space-related information processing seems to be determined by otolithic organ information rather than semicircular canals. Due to otolithic function impairment, spatial learning was impaired after exposure to gravity changes in animals and this impaired performance was compensated after normal gravity exposure.

Effects of Abnormal Phlegmatic Munziq on Ability of Learning and Memory and Protein Expressions of Brain Tissue RAGE and LRP1 of APP/PS1 Transgenic Mice Model of AD / 中国中医药信息杂志

Objective To investigate the effects of Abnormal Phlegmatic Munziq on ability of learning and memory, and protein expressions of brain tissue RAGE and LRP1 of APP/PS1 transgenetic mice model of AD;To discuss its mechanism of action. Methods Three-month-old APP/PS1 transgenic mice were randomly divided into 5 groups: model control group, positive control group, Abnormal Phlegmatic Munziq high-, medium-, and low-dose groups, 18 mice in each group. Another 18 three-month-old C57BL/6J mice were chosen as normal control group. All administration groups received relevant medicine for successive 6 months. Then the changes in ability of learning and memory of mice were detected by Step-down test; protein expressions of LRP1 and RAGE were detected by immunohistochemistry and Western blot. Results Compared with the normal control group, the reaction time of learning grades and the mistake times increased, incubation of memory grades decreased and the mistake times increased in the model control group (P<0.01);Compared with the model control group, the reaction time of learning grades and the mistake times decreased, incubation of memory grades increased and the mistake times decreased in all administration groups (P<0.05, P<0.01). Immunohistochemistry and Western blot results showed that compared with normal control group, the LRP1 expression decreased and RAGE increased in the model control group (P<0.05);Compared with the model control group, the LRP1 expression decreased and RAGE increased in Abnormal Phlegmatic Munziq high-, medium-, and low-dose groups (P<0.05,P<0.01). Conclusion Abnormal Phlegmatic Munziq can improve ability of spatial learning and memory in APP/PS1 mice and regulate the expressions of RAGE and LRP1.

Effects of Siwu Decoction on Memory and Spatial Learning in Mice with Blood Deficiency and Related Mechanisms / 医药导报

Objective To investigate the effects of Siwu decoction on the learning and memory abilities in mice with blood deficiency and the related mechanism.Methods The mice were randomly divided into five groups:normal control group,model control group,high-,medium-,and low-dose group of Siwu decoction.Blood deficiency mouse model was established by continuously cuttingtailand bleedingin model control group,high-,medium-,and low-dose group of Siwu decoction.The mice in high-,medium-,and low-dose group were intragastrically administrated with Siwu decoction of 2.5,5.0,10.0 g·kg-1 for 14 days,respectively.The erythrocyte counts (RBC),hemoglobin (HGB),red blood cell hematocrit (HCT) were detected before modeling,7 and 14 days after administration.The spatial learning and memory abilities were assessed using the T maze test.The spontaneous activities were assessed using locomotors activity detector.The levels of erythropoietin (EPO) content in serum and acetylcholinesterase (AChE) in hippocampal tissue were detected by enzyme-linked immunousorbent assay.Results 5.0 and 10.0 g·kg-1Siwu decoction could increase RBC,HGB,HCT on the 7th and 14th day,2.5 g.kg-1Siwu decoction could increase RBC,HCT on 14th day,and each dosage of Siwu decoction could significantly increase the spontaneous activities of model mice with blood deficiency on the 7th and 14th day as compared with model control group (P ＜0.05 or P ＜0.01).Compared with model control group,the number of errorsin T Maze test were decreased significantly in high-,medium-,and low-dose groups (P ＜ 0.01).And the Siwu decoction had a tendency to reduce the hippocampal AChE levels,but when compared with the model control group there were no statistical differences (P ＞ 0.05).Conclusion Siwu decoction is benefit formemory and spatial learning in mice with blood deficiency,which may be related with higher serun EPO and lower hippocampal AChE expression.

Effect of Icariside Ⅱ on spatial learning and memory impairments and axonal regeneration in rats induced by chronic cerebral hypoperfusion / 中华行为医学与脑科学杂志

Objective To observe the effect of IcarisideⅡ (ICSⅡ) on spatial learning and memory impairments and axonal regeneration induced by chronic cerebral hypoperfusion (CCH) in rats.Methods 90 male SD rats were randomly divided into normal group,sham operation group,CCH group and ICS Ⅱ low,middle and high-dose treatment groups.The chronic cerebral hypoperfusion model was established by permanent bilateral common carotid artery occlusion.Then these rats in ICS Ⅱ low,middle and high-dose treatment groups were given ICS Ⅱ4,8 and 16 mg/(kg · d) by gavage on the 1st day after modeling.There were 5 rats in every group at each observing time(4,8 and 12 week).Morris water maze experiment was utilized to assess the escape latency and the target quadrant residence time while HE and immunohistochemistry analysis were applied to test the morphology change and expressions of GAP-43,MAP-2 and Nogo-A in hippocampal CA 1.Results Compared with those of sham operation groups at 4,8 and 12 week respectively,the escape latency in CCH group were significantly prolonged(40.02±4.95) s,(42.29±5.75) s,(53.68±6.14) s vs (26.43±2.68) s,(26.84±2.06) s,(31.53±4.12) s,P＜0.05;the target quadrant residence time were significantly reduced(28.53±2.40) s,(28.02±4.28) s,(22.60±4.03) s vs (33.34±2.89) s,(33.31 ±4.14) s,(31.63±2.20)s,P＜0.05);the expressions of GAP-43 and Nogo-A were increased with that of MAP-2 reduced(P＜0.05).Meanwhile,the neuropathological changes with more denatured neurons and less normal neurons were found in hippocampal CA1.However,compared with those of CCH group,the escape latency of ICS Ⅱ middle and high-dose groups (30.58±3.03) s,(29.19±4.23) s,(38.77±5.80) s;(28.90±2.98) s,(26.91 ±6.63) s,(36.51 ±3.98) s) were shortened (P＜0.05);the target quadrant residence time (32.54± 3.41) s,(32.69±3.47) s,(28.27±3.57) s;(32.69±3.54) s,(33.20±4.29) s,(28.07±4.04) s) were increased (P＜ 0.05);the expression of Nogo-A was decreased while those of GAP-43 and MAP-2 were conversely increased (P＜0.05).Moreover,few denatured neurons were observed in hippocampal CA1.But there were no differences for those indexs between CCH group and ICS Ⅱ low-dose treatment groups (P＞0.05).Compared with those in 8 week and 4 week,the escape latency and the target quadrant residence time were prolonged and reduced with the expression of Nogo-A increased in all groups except normal group and sham operation group(P＜0.05),the expressions of GAP-43 and MAP-2 were decreased in CCH group and ICS Ⅱ low-dose treatment group(P＜0.05),but there were no significant differences in ICS Ⅱ middle and high-dose treatment groups at 12 week(P＞0.05).However,there were no statistical significance of all indexes between 8 week and 4 week(P＞0.05).Conclusion ICS Ⅱ can improve the spatial learning and memory in chronic cerebral hypoperfusion rats,which may be achieved by neuroprotective effects and reducing the expression of Nogo-A consequently promotes the regeneration of axons.

Long-term Impairment of Spatial Learning and Memory in Rats after Heat Stroke / 中国康复理论与实践

Objective To compare the spatial learning and memory function of heat stroke rats in different periods, to explore the long-term impairment. Methods 42 Sprague-Dawley rats were randomly divided into heat stroke 7 days group (HS7, n=21), heat stroke 21 days group (HS21, n=21), and another 18 rats were performed femoral artery intubation as surgery control group (sham, n=18). They were tested with Morris water maze 7 days and 21 days after modeling respectively for 5 days. The escaping latency, the frequency of crossing the platform area and the duration in the target quadrant were recorded. Results Compared with the sham group, the escaping latency prolonged in HS7 group in all the time (P0.05). Conclusion The impairment of spatial learning and memory is the most seriously 7 days after heat stroke in rats, and it may remain for long time.

Effects of Abnormal Phlegmatic Temperament Granules on Behavioristics and Hippocampus Pathomorphism of APP/PS1 Transgenic Mice / 中国中医药信息杂志

Objective To investigate the effects of Abnormal Phlegmatic Temperament Granules on spatial learning and memory, histopathology morphological change in hippocampus CA1 zone; To discuss its mechanism of action.Methods Three-month-old APP/PS1 transgenic mice were randomly divided into 5 groups: model control group, positive control (donepezil 0.92 mg/kg) group, Abnormal Phlegmatic Temperament Granules high-, medium-, and low-dose groups (3, 2, 1.5 g/kg), 18 mice in each group. Another 18 three-month-old C57BL/ 6J mice were chosen as normal control group. All administration groups received relevant medicine for successive 6 months. Then the changes in learning and memory ability of mice were detected by Morris water maze test; pathomorphism in hippocampus CA1 zone was detected by HE staining method; changes of myelin sheath, microtubule, and microfilament in myelinated nerve of hippocampus CA1 zone were detected by electron microscope. Results Morris water maze test results showed that escape incubation period of APP/PS1 transgenic mice was significantly longer than the normal control group (P<0.01), and the original platform time was significantly shorter than normal control group (P<0.01); compared with model control group, Abnormal Phlegmatic Temperament Granules treatment groups escape latency time was significantly reduced (P<0.05, P<0.01). Space experiments and escape incubation period of Abnormal Phlegmatic Temperament Granules high-, medium-, low-dose groups were significantly shortened (P<0.05, P<0.01), and spatial searching test showed that the times of mice in Abnormal Phlegmatic Temperament Granules high-, medium-, low-dose groups passing through effective area increased (P<0.01). The integrity of HE staining pyramidal cell layer in the hippocampus CA1 zones of Abnormal Phlegmatic Temperament Granules high-, medium-, and low-dose groups was relatively good; cells arranged orderly; distribution was normal. Electron microscopic observation showed that compared with model control group, the hippocampus neurons nuclear had irregular shape; nuclear membrane was clear and complete; chromatin was clear; nucleolus was obvious; cell matrix was uniform; organelles were abundant; mitochondrial cristae was obvious; endoplasmic reticulum and free ribosomes were obvious. Conclusion Abnormal Phlegmatic Temperament Granules can improve spatial learning and memory in APP/PS1 mice, alleviate neuronal ultrastructure damage and ultimately improve cognitive function.