Investigating Morphological Changes of the Hippocampus After Prolonged Aerobic Exercise in Mice: Neural Function and Learning Capabilities

SUMMARY: Both the academic and popular worlds have paid close attention to the link between exercise and cognitive performance. It is increasingly important to understand the numerous mechanisms by which exercise might influence cognitive abilities in view of the continuous societal issues caused by aging populations and the prevalence of disorders associated to cognitive decline. A rising amount of evidence showing a favorable association between physical activity and cognitive well-being serves as the foundation for the justification for studying the effects of exercise on cognitive function and learning ability. The study employed an 8-week treadmill based on exercise on male adults C57BL/6 mice. The exercise group were engaged in 5 sessions a week gradually increasing the intensity of the protocol by 5 % each week. The Mice cognitive assessments were done using Morris Water Maze and Novel Object Recognition tests. The long term-impact on learning ability were further assessed through immmohistochemistry and molecular analysis of the hippocampal and prefrontal cortex tissues of the animals' brain tissues. The findings showed improved spatial learning abilities, recognition memory, and heighted synaptic plasticity indicated by elevated synaptic makers. The study underscores the role of long-term aerobic exercise in augmenting cognitive performance. It not only contributes to the understanding of the interplay between neuroplasticity and cognitive benefits but also the growing body of research on the impact of exercise on cognitive function.

Tanto el mundo académico como el popular han prestado mucha atención al vínculo entre el ejercicio y el rendimiento cognitivo. Es cada vez más importante comprender los numerosos mecanismos por los cuales el ejercicio podría influir en las capacidades cognitivas en vista de los continuos problemas sociales causados por el envejecimiento de la población y la prevalencia de trastornos asociados al deterioro cognitivo. Una cantidad cada vez mayor de evidencia que muestra una asociación favorable entre la actividad física y el bienestar cognitivo sirve como base para justificar el estudio de los efectos del ejercicio sobre la función cognitiva y la capacidad de aprendizaje. El estudio se realizó en ratones machos adultos C57BL/6 utilizándose en los ejercicios una cinta rodante durante 8 semanas. El grupo de ejercicio realizó 5 sesiones por semana aumentando gradualmente la intensidad del protocolo en un 5 % cada semana. Las evaluaciones cognitivas de los ratones se realizaron utilizando las pruebas Morris Water Maze y Novel Object Recognition. El impacto a largo plazo en la capacidad de aprendizaje se evaluó mediante inmunohistoquímica y análisis molecular de los tejidos del hipocampo y la corteza prefrontal de los tejidos cerebrales de los animales. Los hallazgos mostraron mejoras en las habilidades de aprendizaje espacial, la memoria de reconocimiento y una mayor plasticidad sináptica indicada por unos creadores sinápticos elevados. El estudio subraya el papel del ejercicio aeróbico a largo plazo para aumentar el rendimiento cognitivo. No sólo contribuye a la comprensión de la interacción entre la neuroplasticidad y los beneficios cognitivos, sino también al creciente conjunto de investigaciones sobre el impacto del ejercicio en la función cognitiva.

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.

α-Lipoic acid improves spatial learning memory deficits induced by intracerebroventricular injection of streptozotocin via activation of JAK/STAT-GPX4 in rats / 中华内分泌代谢杂志

Objective:To observe the effect of α-lipoic acid(ALA) on the intracerebroventricular injection(icv) of streptozotocin(STZ)-induced spatial learning memory impairments in rats and the underlying molecular mechanisms.Methods:Forty-five male SD rats were assigned into 3 groups, control group, icv-STZ group and icv-STZ+ ALA group, 15 rats each. STZ was dissolved in artificial cerebrospinal fluid then injected into the lateral ventricles of the rat by using stereotaxic device. ALA was administrated by gavage after STZ injection. The spatial learning memory was examined by using Morris water maze test after 4 weeks of treatment. Immunohistochemistry was performed to detect the number of microglia and astrocytes, electron microscopy was applied to detect mitochondrial integrity, Western blotting was used to detect the protein expression levels, and the changes of lipid peroxidation and redox system were examined by kit.Results:Spatial learning memory was impaired in rats after 4 weeks of STZ injection, and ALA treatment ameliorated STZ-induced cognitive dysfunction in rats. Iron concentration, lipid peroxidation, neuroinflammation, Tau hyperphosphorylated were enhanced markedly after STZ injection, along with and the activation of MAPK and GSK-3β, which were ameliorated by ALA. Further examination revealed that STZ activated the JAK2/STAT3 pathway and transcriptionally inhibited the expression of peroxidase GPX. Inhibition of STAT3 activity can block STZ-induced downregulation of GPX4 and Tau hyperphosphorylation.Conclusion:ALA ameliorated STZ-induced spatial learning memory impairments in rats via deactivation of JAK2/STAT3 pathway, restored GPX4 protein level, resulting in chelating iron, improving mitochondrial function, balancing the redox system, ameliorating Tau hyperphosphorylation and neuroinflammation.

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.

Effect of astragaloside IV on improvement of spatial learning and memory abilities and its mechanism in vascular dementia rat models of chronic cerebral ischemia / 中华神经医学杂志

Objective:To investigate whether astragaloside (AST) IV can improve spatial learning and memory abilities by alleviating oxidative stress damage to the frontal cortex and hippocampus in vascular dementia (VD) rats induced by chronic cerebral ischemia.Methods:Totally, 72 adult male Wistar rats were randomly assigned to four groups: sham-operated group ( n=12), model group ( n=20), AST-IV 10 mg group ( n=20), and AST-IV 20 mg group ( n=20); chronic cerebral ischemia-induced VD models in the later three groups were established by permanent bilateral common carotid artery occlusion (BCCAO); 3 h after BCCAO, these rats were administered with saline, 10 mg/kg AST-IV, or 20 mg/kg AST-IV once daily for a consecutive 90 d. Ninety-four d after modeling, spatial learning and memory abilities were assessed by Morris water maze; the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT), and malondialdehyde (MDA) levels were measured by enzyme linked immunosorbent assay (ELISA). The levels of lipid peroxidation and oxidative DNA damage were assessed by immunohistochemical staining for 4-hydroxynonenal (4-HNE) and 8-hydroxy20-deoxyguanosine (8-OhdG), respectively. Results:(1) On the 3 rd, 4 th and 5 th d of place navigation test, the escape latency in rats of the model group was significantly longer than that in the sham-operated group, and that in the AST-IV 20 mg group was significantly shorter than that in the model group ( P<0.05); spatial probe test showed that the time percentage of rats spending in platform region in the model group (20.3%±1.7%) was significantly smaller than that in the sham-oprated group (48.2%±3.6%), and that in the AST-IV 20 mg group (39.7%±3.2%) was significantly larger than that in the model group ( P<0.05). (2) As compared with those in the sham-operated group, the SOD, GSH-Px and CAT activities were statistically decreased while MDA level was significantly increased in the frontal cortex and hippocampal CA1 area of rats in the model group ( P<0.05); as compared with those in the model group, the SOD, GSH-Px and CAT activities were statistically increased while MDA level was significantly decreased in the frontal cortex and hippocampal CA1 area of rats in the AST-IV 20 mg group ( P<0.05). (3) As compared with those in the model group, the numbers of 4-HNE and 8-oHdG positive cells in the frontal cortex and hippocampal CA1 area of rats in the AST-IV 20 mg group were significantly smaller ( P<0.05). Conclusion:Intraperitoneal injection of high dose AST-IV can ameliorate oxidative damage in the frontal cortex and hippocampal CA1 area in chronic cerebral ischemia-induced VD models, and has the potential to reverse spatial learning damages and memory dysfunction.

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.

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.

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.

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.

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.

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.

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.

Effect of Jin's 3-needling therapy on executive function and spatial learning and memory abilities of frontal lobe injury rats / 中华神经医学杂志

Objective To investigate the effect of Jin's 3-needling therapy on executive function and spatial learning and memory abilities and their mechanism in frontal lobe injury rats. Methods Thirty-two male Sprague-Dawley rats were randomly divided into sham-operated group, Jin's 3-needling group, model group and medoba treatment group (n=8). The rats in the sham-operated group only underwent craniotomy to remove the bone flap and no impact was performed on the frontal lobe; the frontal lobe injury models of model group, Jin's 3-needling group and medoba treatment group were established by eCCI-6.3 device; rats in the Jin's 3-needling group were treated with Jin's 3-needling therapy, and rats in the madopa treatment group were given 2 mL of madopa suspension by perfusion once daily. The behavior of rats in each group was evaluated by GO/NO GO task and Morris water maze test, and apoptosis of cells was detected by TUNEL, dopamine receptor D1 (DRD1) expression was determined by immunohistochemistry, and the content of dopamine in frontal tissues was analyzed by high performance liquid chromatography. Results The accuracy rate of GO/NO GO task in Jin's 3 needling group was significantly higher than that in madopa treatment group (P<0.05); and that in madopa treatment group was significantly higher than that in model group (P<0.05). On the 3rd and 4th d of place navigation test, the escape latency in the Jin's 3 needling group and madopa treatment group was significantly decreased as compared with that in the model group (P<0.05); the escape latency in the Jin's 3 needling group was significantly decreased as compared with that in the madopa treatment group (P<0.05). In spatial probe test, the number of times of crossing the platform in the Jin's 3 needling group and madopa treatment group was significantly larger as compared with that in the model group (P<0.05). As compared with those in the model group, the number of apoptotic neurons in the frontal lobes was significantly larger, the content of dopamine in the frontal lobes and the DRD1 expression were significantly increased in the madopa treatment group and Jin's 3-needling group (P<0.05); the number of apoptotic neurons in the Jin's 3 needling group was significantly smaller as compared with that in the madopa treatment group (P<0.05); the content of dopamine in the frontal lobes and the DRD1 expression in the Jin's 3 needling group were significantly increased as compared with those in the madopa treatment group (P<0.05). Conclusion Jin's 3-needling therapy can effectively improve the executive function and spatial learning and memory abilities of frontal lobe damaged rats, and their mechanism may be related to decreased apoptosis of frontal tissue cells and increased dopamine content and increased DRD1 expression.

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.

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.