Evidências de validade do teste informatizado para avaliação das funções executivas / Evidence of validity of the computerized test for evaluating executive functions / Evidencia de validez de la prueba computarizada para evaluación de funciones ejecutivas

Funções executivas (FE) referem-se ao conjunto de habilidades que, de forma integrada, coordenam o comportamento e a cognição. Assim, o comprometimento no desenvolvimento das FE está ligado a vários desfechos negativos ao longo da vida. Portanto, a avaliação dessas habilidades na infância é essencial para identificar e prevenir prejuízos na vida adulta. Este estudo teve como objetivo investigar evidências de validade do Teste Informatizado para Avaliação das Funções Executivas (Tafe) pelo critério de idade e pelo padrão de correlação entre medidas do TAFE e outras medidas de FE. Para isso, foi utilizada uma amostra de 51 crianças, entre 4 e 10 anos de idade, matriculadas em uma escola privada na cidade de Goiânia (GO), da pré-escola ao 4º ano do ensino fundamental. Como instrumentos, foram utilizados, além do Tafe, as tarefas de Bloco de Corsi, Teste de Trilhas A e B, Teste de Trilhas Pré-Escolares, Teste de Stroop Pré-Escolares e Subteste Dígitos da Escala Wechsler de Inteligência. Foram conduzidas análises estatísticas Kruskal Wallis para verificar a evidência de validade por relação com idade e análises de correlação não paramétrica de Spearman para avaliar as evidências de validade convergente. O instrumento investigado mostrou-se efetivo para discriminar entre as diferentes faixas etárias, assim, sensível ao desenvolvimento das FE. Os resultados obtidos no Tafe correlacionaram-se aos obtidos em outros testes que também avaliaram FE, mostrando claros padrões de convergência. Logo, as análises dos resultados fornecem evidências de validade ao Tafe, derivadas a partir de diferentes estratégias de investigação.(AU)

Executive functions (EF) refer to the set of skills that, in an integrated way, coordinate behavior and cognition. Thus, the commitment in developing EF is linked to several negative outcomes throughout life. Therefore, the assessment of these abilities in childhood is essential to identify and prevent possible harm in adult life. This study aimed to investigate evidences of validity of the Computerized Test for Evaluation of Executive Functions (TAFE) by the age criterion and by the pattern of correlation between TAFE measures and other EF measures. To this end, a sample of 51 children, between 4 and 10 years old, enrolled in a private school in the municipality of Goiânia (GO), from preschool to the 4th year of elementary school, was used. As instruments, in addition to TAFE, the tasks of Corsi Block, Trails Test A and B, Preschool Trails Test, Preschool Stroop Test and the Digits Subtest of the Wechsler Intelligence Scale were used. Kruskal Wallis statistical analyzes were conducted to verify the evidence of validity by age criteria and Spearman's nonparametric correlation analysis to assess evidence of convergent validation. The instrument investigated was effective to discriminate between different age groups, thus being sensitive to the development of EF. The results obtained in TAFE were correlated with those obtained in other tests that also assess FE, showing patterns of convergence. Therefore, the analysis of the results provides validation evidence to TAFE, derived from different investigation methods.(AU)

Las funciones ejecutivas (FE) se refieren al conjunto de habilidades que coordinan la conducta y la cognición. Así, el deterioro en el desarrollo de FE está relacionado con varios resultados negativos durante la vida. Por tanto, la valoración de estas habilidades en la infancia es fundamental para identificar y prevenir posibles daños en la vida adulta. Este estudio tuvo como objetivo investigar la evidencia de validez de la Prueba Computarizada para Evaluación de Funciones Ejecutivas (Tafe) por el criterio de edad y convergencia entre las medidas Tafe y otras medidas de FE. Para ello, se utilizó una muestra de 51 niños, de entre 4 y 10 años de edad, matriculados en un colegio privado de Goiânia (Goiás, Brasil) desde la preescolar hasta 4.º de primaria. Como instrumentos, además del Tafe, se utilizaron las tareas de Bloque de Corsi, el Test de los senderos A y B, el Test de los Senderos Preescolares, el Test de Stroop Preescolar y la Subprueba de Dígitos de la Escala Wechsler de Inteligencia. Se realizaron análisis estadísticos de Kruskal Wallis para verificar la validez por criterios de edad y análisis de correlación no-paramétrica de Spearman para evaluar la evidencia de validez convergente. Tafe demostró ser efectivo para discriminar entre diferentes grupos de edad, así es sensible al desarrollo de FE. Los resultados en Tafe se correlacionaron con los obtenidos en otras pruebas de FE, lo que muestra claros patrones de convergencia. Por tanto, el análisis aporta evidencias de validez para Tafe, derivadas de diferentes estrategias de investigación.(AU)

Reflexões sobre o trabalho on-line da neuropsicologia infantil numa visão histórico-cultural / Reflections on the online work of child neuropsychology from a cultural-historical perspective / Reflexiones sobre el trabajo online de la neuropsicología infantil desde una perspectiva histórico-cultural

O isolamento social provocado pela pandemia de covid-19 exigiu uma intensificação no estabelecimento de parâmetros para o trabalho do neuropsicólogo com suas especificidades. Assim, o objetivo deste artigo é levantar reflexões sobre a prática neuropsicológica infantil via internet baseada na nossa experiência prática vivenciada no período, relacionando com as referências teóricas da abordagem histórico-cutural e outros trabalhos que discorrem sobre as particularidades dessa modalidade de atendimento. Para isso, foi realizada uma pesquisa bibliográfica em fontes reconhecidas, como SciELO e Google Acadêmico, utilizando-se marcadores como "neuropsicologia on-line" e "teleneuropsicologia", entre outros, em português, inglês e espanhol. Os trabalhos encontrados foram utilizados como fundamento para discutir as ideias aqui apresentadas, a partir da experiência dos autores durante esse período. Considera-se que os neuropsicólogos precisam enfrentar a possível necessidade do trabalho on-line, considerando que as situações vividas durante a pandemia tendem a aumentar a necessidade de avaliações e intervenções neuropsicológicas. Ao mesmo tempo, se prevê que essa via de trabalho deve se intensificar após o isolamento, dentro do que se tem denominado como "o novo normal". Para isso, é essencial que haja esforço por parte da comunidade neuropsicológica para mostrar como essa área de trabalho pode ser útil para crianças, seus pais e professores. Conclui-se que é preciso ter a noção de que nenhuma via ou metodologia de trabalho é absolutamente completa, sendo essencial a instrumentalização das vantagens e desvantagens de todas elas.(AU)

The social isolation caused by the COVID-19 pandemic demanded intensification in the establishment of parameters for the neuropsychologist's work with its specificities. Thus, the aim of this article is to raise reflections on child neuropsychological practice via the internet, based on our practical experience in this period, relating to the theoretical references of the cultural-historical approach and other works that discuss the particularities of this type of care. For this, a bibliographic research was carried out in recognized sources such as SciELO and Google Scholar, using markers such as "online neuropsychology" and teleneuropsychology, among others, in Portuguese, English and Spanish. The works found were used as a basis for discussing the ideas presented here which are based on the authors' experience during this period. It is considered that neuropsychologists need to face the possible need for online work, considering that situations experienced during the pandemic tend to increase the need for neuropsychological assessments and interventions. At the same time, it is expected that this work path should intensify after isolation, within of what has been called "the new normal". For this, an effort by the neuropsychological community is essential to show how this area of work can be useful for children, their parents and teachers. It is concluded that it is necessary to have the notion that no way or work methodology is absolutely complete, being essential the instrumentalization of the advantages and disadvantages of all of them.(AU)

El aislamiento social provocado por la pandemia de Covid-19 exigió una intensificación en el establecimiento de parámetros para el trabajo del neuropsicólogo con sus especificidades. Así, el objetivo de este artículo es plantear reflexiones sobre la práctica neuropsicológica infantil a través de internet, a partir de nuestra experiencia práctica en este período, en relación con los referentes teóricos del enfoque histórico-cultural y otros trabajos que discuten las particularidades de este tipo de cuidado. Para esto, se realizó una investigación bibliográfica en fuentes reconocidas como SciELO y Google Académico, utilizando marcadores como "neuropsicología en línea" y teleneuropsicología, entre otros, en portugués, inglés y español. Los trabajos encontrados sirvieron de base para discutir las ideas aquí presentadas a partir de la experiencia de los autores durante este período. Se considera que los neuropsicólogos necesitan enfrentar la posible necesidad de trabajo en línea, considerando que las situaciones vividas durante la pandemia tienden a incrementar la necesidad de evaluaciones e intervenciones neuropsicológicas. Al mismo tiempo, se espera que esta vía de trabajo se intensifique después del aislamiento, dentro de lo que se ha denominado "la nueva normalidad". Para esto, un esfuerzo de la comunidad neuropsicológica es fundamental para mostrar cómo esta área de trabajo puede ser útil para los niños, sus padres y profesores. Se concluye que es necesario tener la noción de que ninguna vía o metodología de trabajo es absolutamente completa, siendo imprescindible la instrumentalización de las ventajas y desventajas de todas ellas.(AU)

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.

Roles of c-Fos, EGR-1, PKA, and PKC in cognitive dysfunction in rats after propofol anesthesia

Abstract This study aimed to investigate possible changes in the spatial memory of rats and the expression or activity of EGR-1, c-Fos, PKA, and PKC after propofol anesthesia. Thirty-six Sprague-Dawley rats aged 20 months and 36 Sprague-Dawley rats aged three months were each randomly divided into three groups: the control group, the Morris Water Maze (MWM) group, and the propofol group. In the propofol groups of both young and aged rats, the rats were anesthetized by propofol for two or four hours and then performed the MWM test two days or two weeks after anesthesia to assess cognitive function. EGR-1, c-Fos, PKA, and PKC expressions in the rat hippocampus were determined via immunohistochemistry. For the older rats, the escape latency in the P4h/2d group was significantly prolonged (P < 0.05), and the learning curve was right-shifted in the P4h/2w group (P < 0.05). The expression levels of EGR-1, c-Fos, PKA, and PKC in the MWM groups were significantly higher than those in the control groups (P < 0.05). In the P4h/2d group of aged rats, the expression levels of both PKA and PKC were decreased compared with those of the MWM groups. The decreased expression of both protein kinases may be responsible for the observed impairment after propofol anesthesia

Cognitive training using the abacus: a literature review study on the benefits for different age groups / Treino cognitivo com o uso do ábaco: um estudo de revisão da literatura sobre os benefícios para os diferentes grupos etários

ABSTRACT. The literature indicates that cognitive stimulation interventions have shown promising results. Abacus represents a tool with great potential in such interventions. Objectives: To carry out a systematic review of studies published in recent years that entailed the delivery of a cognitive training program using an abacus to boost target cognitive abilities of older persons and also other age groups, with or without cognitive impairment. Methods: A systematic review study was conducted in July 2020 involving PubMed, MedLine, LILACS, and SciELO databases. Results: A total of 29 studies were retrieved, of which 8 aimed to identify the effect of abacus-based mental calculation (AMC) for different age groups and to determine its applicability as a method of cognitive stimulation for older adults. In AMC technique, participants first learn to use the physical abacus (PA) and after achieving proficiency they perform calculations using a mental image of the device, manipulating the beads of the so-called mental abacus (MA). Conclusions: The number of studies addressing abacus use as a cognitive training tool was rather limited, considering the relevance of the theme. Their interventions have shown benefits for cognitive functioning of individuals of various age groups, including older adults with cognitive impairment. Future studies that involve larger samples of healthy and/or cognitively impaired older adults with a longitudinal design and a more elaborate methodological design are suggested.

RESUMO. A literatura aponta que intervenções de estimulação cognitiva têm mostrado resultados promissores. O ábaco representa uma ferramenta com grande potencial nesse tipo de intervenções. Objetivo: Realizar uma revisão sistemática de estudos publicados nos últimos anos que buscaram, em seus métodos, oferecer um programa de treino cognitivo com o uso do ábaco para estimular habilidades-alvo em idosos e em pessoas de outras faixas etárias, com ou sem comprometimento cognitivo. Métodos: Estudo de revisão sistemática, realizado em julho de 2020, utilizando-se as bases de dados PubMed, MedLine, LILACS e SciELO. Resultados: Um total de 29 estudos foram encontrados, dos quais oito objetivaram identificar o efeito do treino de uma técnica chamada abacus-based mental calculation (AMC) em diferentes faixas etárias e verificar sua aplicabilidade como método de estimulação cognitiva para idosos. No AMC, os participantes aprendem inicialmente a manipular o ábaco físico (PA, na sigla em inglês) e, após adquirirem agilidade, passam a realizar cálculos com uma imagem mental do instrumento, manipulando as contas do denominado ábaco mental (MA, na sigla em inglês). Conclusões: O número de estudos que abordaram o uso do ábaco como ferramenta para realização de treino cognitivo foi bastante limitado diante da relevância do tema. Os estudos analisados apresentaram benefícios do treino cognitivo com uso do ábaco para o desempenho cognitivo de indivíduos de diversas faixas etárias, inclusive em idosos com comprometimento cognitivo. Para estudos futuros, espera-se a realização de mais pesquisas com amostras maiores, com delineamento longitudinal e com métodos bem elaborados, com enfoque em pessoas idosas, saudáveis e/ou com comprometimento cognitivo.

Long-term exposure to high altitude affects spatial working memory in migrants-evidence from time and frequency domain analysis / 生理学报

Long-term exposure to high altitude affects spatial working memory. Previous studies have focused on the analysis of electroencephalogram (EEG) components in time domain rather than in frequency domain. To explore the influence of long-term high altitude exposure on time dynamic characteristics and neural oscillation process of the spatial working memory, n-back task combined with the technology of event related potential recording was performed on 20 young migrants who grew at low altitude before the age of 18 and moved to high altitude more than three years ago, and 21 young people who had never been to the high altitude. EEG data were recorded, and the time domain and frequency domain analyses were performed. The results showed that the response time was longer and the accuracy rate was lower under the 2-back condition in the high altitude group compared with those in low altitude group. The late positive potential (LPP) amplitude was more negative, P2 amplitude was more positive in the 2-back condition, and the power value of early delta frequency band (1-4 Hz, 160-300 ms) was larger, while the power values of late delta frequency band (1-4 Hz, 450-650 ms) and theta frequency band (4-8 Hz, 450-650 ms) were smaller in the high altitude group compared with those in low altitude group. The results suggested that long-term exposure to high altitude affected the spatial working memory ability of the migrants, which was reflected in the lack of attention resources in the later matching stage, decreased response inhibition ability and information maintenance ability, and thus resulted in impaired spatial working memory.

Progress in the encoding characteristics and mechanisms of hippocampal neural assemble sequences in spatial memory / 生理学报

The formation, consolidation and retrieval of spatial memory depend on sequential firing patterns of place cells assembling in the hippocampus. Theta sequences of place cells during behavior play a role in acquisition of spatial memory, trajectory prediction and decision making. In awake rest and slow wave sleep, place cell sequences occur during the sharp wave-ripples (SWRs), called "replay", which is crucial for memory consolidation and retrieval. In this review, we summarize the functional significances of theta sequences and SWRs replay sequences and the mechanism of these sequences. We also discuss the relationship between theta and replay sequences with the formation of spatial memory. We propose the research direction in this field in future and aim to provide new ideas for related researches.

Chronic stress increases dopamine levels in hippocampal dentate gyrus and impairs spatial learning and memory in rats / 生理学报

The objective of this study was to elucidate the effect of chronic stress (CS) on dopamine (DA) level and synaptic efficiency in the hippocampal dentate gyrus (DG) during spatial learning and memory. Sprague Dawley (SD) male rats were randomly divided into control group and CS group (n = 10). CS group was treated with chronic mild unpredictable stress, and control group did not receive any treatments. The levels of epinephrine and corticosterone (CORT) in serum were measured by using enzyme-linked immunosorbent assay (ELISA); the spatial learning and memory abilities of rats were measured by Morris water maze (MWM) test. Meanwhile, the amplitude of field excitatory postsynaptic potential (fEPSP) and concentration of DA in the DG region were determined by in vivo electrophysiology, microdialysis and HPLC techniques during MWM test in rats. After that, the DA D1 receptor (D1R) and its key downstream members in DG were examined by immunohistochemistry or Western blot assay. The results showed that the levels of epinephrine and CORT in the serum of the rats in CS group were significantly increased compared with those in the control group (P < 0.05). In CS group rats, the escape latency was significantly prolonged and the number of platform crossing was markedly decreased during MWM test, compared with those in control group (P < 0.05). Furthermore, the amplitude of fEPSP in the DG was not changed during MWM test in CS rats, while it was significantly increased on the 3rd day of MWM test in control group (P < 0.05). Compared with baseline or control group, CS group showed significantly increased DA level from the 1st to 3rd days of MWM test in the DG (P < 0.05). In addition, the protein expression of D1R was markedly up-regulated in the DG in CS group, while the protein expression levels of p-PKA, p-CREB and BDNF were significantly reduced, compared with those in control group. These results suggest that CS may impair spatial learning and memory abilities in rats through the enhancement of the DA levels in the hippocampal DG.

Exploratory, cognitive, and depressive-like behaviors in adult and pediatric mice exposed to controlled cortical impact

OBJECTIVE: Sequelae of behavioral impairments associated with human traumatic brain injury (TBI) include neurobehavioral problems. We compared exploratory, cognitive, and depressive-like behaviors in pediatric and adult male mice exposed to controlled cortical impact (CCI).METHODS: Pediatric (21 to 25 days old) and adult (8 to 12 weeks old) male C57Bl/6 mice underwent CCI at a 2-mm depth of deflection. Hematoxylin and eosin staining was performed 3 to 7 days after recovery from CCI, and injury volume was analyzed using ImageJ. Neurobehavioral characterization after CCI was performed using the Barnes maze test (BMT), passive avoidance test, open-field test, light/dark test, tail suspension test, and rotarod test. Acutely and subacutely (3 and 7 days after CCI, respectively), CCI mice showed graded injury compared to sham mice for all analyzed deflection depths.RESULTS: Time-dependent differences in injury volume were noted between 3 and 7 days following 2-mm TBI in adult mice. In the BMT, 2-mm TBI adults showed spatial memory deficits compared to sham adults (P < 0.05). However, no difference in spatial learning and memory was found between sham and 2-mm CCI groups among pediatric mice. The open-field test, light/dark test, and tail suspension test did not reveal differences in anxiety-like behaviors in both age groups.CONCLUSION: Our findings revealed a graded injury response in both age groups. The BMT was an efficient cognitive test for assessing spatial/non-spatial learning following CCI in adult mice; however, spatial learning impairments in pediatric mice could not be assessed.

NMDA Receptor Antagonist MK801 Protects Against 1-Bromopropane-Induced Cognitive Dysfunction / 神经科学通报·英文版

Occupational exposure to 1-bromopropane (1-BP) induces learning and memory deficits. However, no therapeutic strategies are currently available. Accumulating evidence has suggested that N-methyl-D-aspartate receptors (NMDARs) and neuroinflammation are involved in the cognitive impairments in neurodegenerative diseases. In this study we aimed to investigate whether the noncompetitive NMDAR antagonist MK801 protects against 1-BP-induced cognitive dysfunction. Male Wistar rats were administered with MK801 (0.1 mg/kg) prior to 1-BP intoxication (800 mg/kg). Their cognitive performance was evaluated by the Morris water maze test. The brains of rats were dissected for biochemical, neuropathological, and immunological analyses. We found that the spatial learning and memory were significantly impaired in the 1-BP group, and this was associated with neurodegeneration in both the hippocampus (especially CA1 and CA3) and cortex. Besides, the protein levels of phosphorylated NMDARs were increased after 1-BP exposure. MK801 ameliorated the 1-BP-induced cognitive impairments and degeneration of neurons in the hippocampus and cortex. Mechanistically, MK801 abrogated the 1-BP-induced disruption of excitatory and inhibitory amino-acid balance and NMDAR abnormalities. Subsequently, MK801 inhibited the microglial activation and release of pro-inflammatory cytokines in 1-BP-treated rats. Our findings, for the first time, revealed that MK801 protected against 1-BP-induced cognitive dysfunction by ameliorating NMDAR function and blocking microglial activation, which might provide a potential target for the treatment of 1-BP poisoning.

The Glutamatergic Postrhinal Cortex-Ventrolateral Orbitofrontal Cortex Pathway Regulates Spatial Memory Retrieval / 神经科学通报·英文版

A deficit in spatial memory has been taken as an early predictor of Alzheimer's disease (AD) or mild cognitive impairment (MCI). The uncinate fasciculus (UF) is a long-range white-matter tract that connects the anterior temporal lobe with the orbitofrontal cortex (OFC) in primates. Previous studies have shown that the UF impairment associated with spatial memory deficits may be an important pathological change in aging and AD, but its exact role in spatial memory is not well understood. The pathway arising from the postrhinal cortex (POR) and projecting to the ventrolateral orbitofrontal cortex (vlOFC) performs most of the functions of the UF in rodents. Although the literature suggests an association between spatial memory and the regions connected by the POR-vlOFC pathway, the function of the pathway in spatial memory is relatively unknown. To further illuminate the function of the UF in spatial memory, we dissected the POR-vlOFC pathway in mice. We determined that the POR-vlOFC pathway is a glutamatergic structure, and that glutamatergic neurons in the POR regulate spatial memory retrieval. We also demonstrated that the POR-vlOFC pathway specifically transmits spatial information to participate in memory retrieval. These findings provide a deeper understanding of UF function and dysfunction related to disorders of memory, as in MCI and AD.

Differential Effects of Pentoxifylline on Learning and Memory Impairment Induced by Hypoxic-ischemic Brain Injury in Rats

OBJECTIVE: Hypoxic-ischemic (HI) brain injury in the human perinatal period often leads to significant long-term neurobehavioral dysfunction in the cognitive and sensory-motor domains. Using a neonatal HI injury model (unilateral carotid ligation followed by hypoxia) in postnatal day seven rats, the present study investigated the long-term effects of HI and potential behavioral protective effect of pentoxifylline. METHODS: Seven-day-old rats underwent right carotid ligation, followed by hypoxia (FiO2 = 0.08). Rats received pentoxifylline immediately after and again 2 hours after hypoxia (two doses, 60–100 mg/kg/dose), or serum physiologic. Another set of seven-day-old rats was included to sham group exposed to surgical stress but not ligated. These rats were tested for spatial learning and memory on the simple place task in the Morris water maze from postnatal days 77 to 85. RESULTS: HI rats displayed significant tissue loss in the right hippocampus, as well as severe spatial memory deficits. Low-dose treatment with pentoxifylline resulted in significant protection against both HI-induced hippocampus tissue losses and spatial memory impairments. Beneficial effects are, however, negated if pentoxifylline is administered at high dose. CONCLUSION: These findings indicate that unilateral HI brain injury in a neonatal rodent model is associated with cognitive deficits, and that low dose pentoxifylline treatment is protective against spatial memory impairment.

Effects of Chronic and Acute Lithium Treatment on the Long-term Potentiation and Spatial Memory in Adult Rats

OBJECTIVE: Although, accumulating evidence is delineating a neuroprotective and neurotrophic role for lithium (Li), inconsistent findings have also been reported in human studies especially. Moreover, the effects of Li infusion into the hippocampus are still unknown. The aims of this work were (a) to assess whether basal synaptic activity and long-term potentiation (LTP) in the hippocampus are different in regard to intrahippocampal Li infusion; (b) to assess spatial learning and memory in rats chronically treated with LiCO₃ in the Morris water maze. METHODS: Field potentials were recorded form the dentate gyrus, stimulating perforant pathways, in rats chronically (20 mg/kg for 40 days) or acutely treated with LiCO₃ and their corresponding control rats. In addition, performance of rats in a Morris water maze was measured to link behaviour of rats to electrophysiological findings. RESULTS: LiCO₃ infusion into the hippocampus resulted in enhanced LTP, especially in the late phases, but attenuated LTP was observed in rats chronically treated with Li as compared to controls. Li-treated rats equally performed a spatial learning task, but did spend less time in target quadrant than saline-treated rats in Morris water maze. CONCLUSION: Despite most data suggest that Li always yields neuroprotective effects against neuropathological conditions; we concluded that a 40-day treatment of Li disrupts hippocampal synaptic plasticity underlying memory processes, and that these effects of prolonged treatment are not associated with its direct chemical effect, but are likely to be associated with the molecular actions of Li at genetic levels, because its short-term effect preserves synaptic plasticity.

Theracurmin Ameliorates Cognitive Dysfunctions in 5XFAD Mice by Improving Synaptic Function and Mitigating Oxidative Stress

As the elderly population is increasing, Alzheimer's disease (AD) has become a global issue and many clinical trials have been conducted to evaluate treatments for AD. As these clinical trials have been conducted and have failed, the development of new theraphies for AD with fewer adverse effects remains a challenge. In this study, we examined the effects of Theracurmin on cognitive decline using 5XFAD mice, an AD mouse model. Theracurmin is more bioavailable form of curcumin, generated with submicron colloidal dispersion. Mice were treated with Theracurmin (100, 300 and 1,000 mg/kg) for 12 weeks and were subjected to the novel object recognition test and the Barnes maze test. Theracurmin-treated mice showed significant amelioration in recognition and spatial memories compared those of the vehicle-treated controls. In addition, the antioxidant activities of Theracurmin were investigated by measuring the superoxide dismutase (SOD) activity, malondialdehyde (MDA) and glutathione (GSH) levels. The increased MDA level and decreased SOD and GSH levels in the vehicle-treated 5XFAD mice were significantly reversed by the administration of Theracurmin. Moreover, we observed that Theracurmin administration elevated the expression levels of synaptic components, including synaptophysin and post synaptic density protein 95, and decreased the expression levels of ionized calcium-binding adapter molecule 1 (Iba-1), a marker of activated microglia. These results suggest that Theracurmin ameliorates cognitive function by increasing the expression of synaptic components and by preventing neuronal cell damage from oxidative stress or from the activation of microglia. Thus, Theracurmin would be useful for treating the cognitive dysfunctions observed in AD.

Effect of Ghrelin on Memory Impairment in a Rat Model of Vascular Dementia

PURPOSE: The purpose of this study was to identify the effect of ghrelin on memory impairment in a rat model of vascular dementia induced by chronic cerebral hypoperfusion. METHODS: Randomized controlled groups and the posttest design were used. We established the representative animal model of vascular dementia caused by bilateral common carotid artery occlusion and administered 80 µg/kg ghrelin intraperitoneally for 4 weeks. First, behavioral studies were performed to evaluate spatial memory. Second, we used molecular biology techniques to determine whether ghrelin ameliorates the damage to the structure and function of the white matter and hippocampus, which are crucial to learning and memory. RESULTS: Ghrelin improved the spatial memory impairment in the Y-maze and Morris water maze test. In the white matter, demyelination and atrophy of the corpus callosum were significantly decreased in the ghrelin-treated group. In the hippocampus, ghrelin increased the length of hippocampal microvessels and reduced the microvessels pathology. Further, we confirmed angiogenesis enhancement through the fact that ghrelin treatment increased vascular endothelial growth factor (VEGF)-related protein levels, which are the most powerful mediators of angiogenesis in the hippocampus. CONCLUSION: We found that ghrelin affected the damaged myelin sheaths and microvessels by increasing angiogenesis, which then led to neuroprotection and improved memory function. We suggest that further studies continue to accumulate evidence of the effect of ghrelin. Further, we believe that the development of therapeutic interventions that increase ghrelin may contribute to memory improvement in patients with vascular dementia.

Long-term Surgical and Chemical Castration Deteriorates Memory Function Through Downregulation of PKA/CREB/BDNF and c-Raf/MEK/ERK Pathways in Hippocampus / 대한배뇨장애요실금학회지

PURPOSE: Goserelin is a drug used for chemical castration. In a rat model, we investigated whether surgical and chemical castration affected memory ability through the protein kinase A (PKA)/cyclic adenosine monophosphate response element-binding protein (CREB)/brain-derived neurotrophic factor (BDNF) and c-Raf/mitogen-activated protein kinases-extracellular signal–regulated kinases (MEK)/extracellular signal–regulated kinases (ERK) pathways in the hippocampus. METHODS: Orchiectomy was performed for surgical castration and goserelin acetate was subcutaneously transplanted into the anterior abdominal wall for chemical castration. Immunohistochemistry was done to quantify neurogenesis. To assess the involvement of the PKA/CREB/BDNF and c-Raf/MEK/ERK pathways in the memory process, western blots were used. RESULTS: The orchiectomy group and the goserelin group showed less neurogenesis and impaired short-term and spatial memory. Phosphorylation of PKA/CREB/BDNF and phosphorylation of c-Raf/MEK/ERK decreased in the orchiectomy and goserelin groups. CONCLUSIONS: Short-term memory and spatial memory were affected by surgical and chemical castration via the PKA/CREB/BDNF and c-Raf/MEK/ERK signaling pathways.

High-Throughput Automatic Training System for Spatial Working Memory in Free-Moving Mice / 神经科学通报·英文版

Efficient behavioral assays are crucial for understanding the neural mechanisms of cognitive functions. Here, we designed a high-throughput automatic training system for spatial cognition (HASS) for free-moving mice. Mice were trained to return to the home arm and remain there during a delay period. Software was designed to enable automatic training in all its phases, including habituation, shaping, and learning. Using this system, we trained mice to successfully perform a spatially delayed nonmatch to sample task, which tested spatial cognition, working memory, and decision making. Performance depended on the delay duration, which is a hallmark of working memory tasks. The HASS enabled a human operator to train more than six mice simultaneously with minimal intervention, therefore greatly enhancing experimental efficiency and minimizing stress to the mice. Combined with the optogenetic method and neurophysiological techniques, the HASS will be useful in deciphering the neural circuitry underlying spatial cognition.

Valproic acid withdrawal ameliorates impairments of hippocampal-spatial working memory and neurogenesis / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Valproic acid (VPA), an agent that is used to treat epileptic seizures, can cause spatial memory impairment in adults and children. This effect is thought to be due to the ability of VPA to inhibit neurogenesis in the hippocampus, which is required for learning. We have previously used an animal model to show that VPA significantly impairs hippocampal-spatial working memory and inhibits neuronal generation in the sub-granular zone of the dentate gyrus. As there are patient reports of improvements in memory after discontinuing VPA treatment, the present study investigated the recovery of both spatial memory and hippocampal neurogenesis at two time points after withdrawal of VPA. Male Wistar rats were given intraperitoneal injections of 0.9% normal saline or VPA (300 mg/kg) twice a day for 10 d. At 1, 30, or 45 d after the drug treatment, the novel object location (NOL) test was used to examine spatial memory; hippocampal cell division was counted using Ki67 immunohistochemistry, and levels of brain-derived neurotrophic factor (BDNF) and Notch1 were measured using western immunoblotting. Spatial working memory was impaired 1 and 30 d after the final administration, but was restored to control levels by 45 d. Cell proliferation had increased to control levels at 30 and 45 d. Both markers of neurogenesis (BDNF and Notch1 levels) had returned to control levels at 45 d. These results demonstrate that memory recovery occurs over a period of six weeks after discontinuing VPA treatment and is preceded by a return of hippocampal neurogenesis to control levels.

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.