RESUMO
Glutamate is involved in fundamental functions, including neuronal plasticity and memory. Astrocytes are integral elements involved in synaptic function, and the GLT-1 transporter possesses a critical role in glutamate uptake. Here, we study the role of GLT-1, specifically located in astrocytes, in the consolidation, expression, reconsolidation and persistence of spatial object recognition memory in rats. Administration of dihydrokainic acid (DHK), a selective GLT-1 inhibitor, into the dorsal hippocampus around a weak training which only induces short-term memory, promotes long-term memory formation. This promotion is prevented by hippocampal administration of protein-synthesis translation inhibitor, blockade of Activity-regulated cytoskeleton-associated protein (Arc) translation or Brain-Derived Neurotrophic Factor (BDNF) action, which are plasticity related proteins necessary for memory consolidation. However, DHK around a strong training, which induces long-term memory, does not affect memory consolidation. Administration of DHK before the test session impairs the expression of long-term memory, and this effect is dependent of Arc translation. Furthermore, DHK impairs reconsolidation if applied before a reactivation session, and this effect is independent of Arc translation. These findings reveal specific consequences on spatial memory stages developed under hippocampal GLT-1 blockade, shedding light on the intricate molecular mechanisms, governed in part for the action of glia.
Assuntos
Astrócitos , Fator Neurotrófico Derivado do Encéfalo , Proteínas do Citoesqueleto , Ácido Glutâmico , Hipocampo , Memória Espacial , Animais , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/fisiologia , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Memória Espacial/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Masculino , Ratos , Proteínas do Citoesqueleto/metabolismo , Proteínas do Citoesqueleto/genética , Ácido Glutâmico/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Proteínas do Tecido Nervoso/antagonistas & inibidores , Proteínas do Tecido Nervoso/genética , Transportador 2 de Aminoácido Excitatório/metabolismo , Transportador 2 de Aminoácido Excitatório/antagonistas & inibidores , Ratos Wistar , Ácido Caínico/farmacologia , Ácido Caínico/análogos & derivados , Consolidação da Memória/efeitos dos fármacosRESUMO
The aim of this study was to evaluate the effects of swimming in the brain and behavior of young and aged mice. Forty-eight male C57BL/6 J mice were randomly distributed into 4 groups (n = 12 per group, 3 and 18 months old). The subdivision of the groups was: 3 months-SED, 18 months-SED, 3 months-EXE, and 18 months-EXE. SED mice did not swim, while EXE mice performed the physical exercise protocol. Training was initiated 48 h after the adaptation week. Swimming sessions consisted of 30 min, with no overload, 5 days per week, for 4 weeks. After the exercise protocol, it was revealed working and spatial memory were impaired in the 18 months-SED group. Pre- and post-synaptic proteins were enhanced in the groups that swam when compared to the 3- and 8 months-SED groups. Lipid peroxidation was greater in the aged mice that did not perform the physical exercise protocol and might have contributed to the cognitive impairment in this group. In conclusion, an aerobic physical exercise protocol, performed through regular swimming sessions, inhibited cognitive impairment, memory loss and lipid peroxidation in the aged mice, while pre- and post-synaptic proteins were enhanced in the hippocampus of young and aged mice.
Assuntos
Envelhecimento , Hipocampo , Peroxidação de Lipídeos , Transtornos da Memória , Camundongos Endogâmicos C57BL , Condicionamento Físico Animal , Natação , Animais , Masculino , Camundongos , Hipocampo/metabolismo , Envelhecimento/fisiologia , Transtornos da Memória/etiologia , Transtornos da Memória/prevenção & controle , Disfunção Cognitiva/prevenção & controle , Disfunção Cognitiva/etiologia , Proteínas do Tecido Nervoso/biossíntese , Memória Espacial/fisiologia , Aprendizagem em Labirinto , Memória de Curto Prazo/fisiologia , Proteína 4 Homóloga a Disks-Large/metabolismo , Sinaptofisina/metabolismoRESUMO
To contribute to research on female models of Alzheimer's disease (AD), our aim was to study the effect of intracerebroventricular (ICV) injection of streptozotocin (STZ) in female rats, and to evaluate a potential neuroprotective action of ovarian steroids against STZ. Female rats were either ovariectomized (OVX) or kept with ovaries (Sham) two weeks before ICV injections. Animals were injected with either vehicle (artificial cerebrospinal fluid, aCSF) or STZ (3 mg/kg) and separated into four experimental groups: Sham + aCSF, Sham + STZ, OVX + aCSF and OVX + STZ. Nineteen days post-injection, we assessed different behavioral aspects: burying, anxiety and exploration, object recognition memory, spatial memory, and depressive-like behavior. Immunohistochemistry and Immunoblot analyses were performed in the hippocampus to examine changes in AD-related proteins and neuronal and microglial populations. STZ affected burying and exploratory behavior depending on ovarian status, and impaired recognition but not spatial memory. STZ and ovariectomy increased depressive-like behavior. Interestingly, STZ did not alter the expression of ß-amyloid peptide or Tau phosphorylated forms. STZ affected the neuronal population from the Dentate Gyrus, where immature neurons were more vulnerable to STZ in OVX rats. Regarding microglia, STZ increased reactive cells, and the OVX + STZ group showed an increase in the total cell number. In sum, STZ partially affected female rats, compared to what was previously reported for males. Although AD is more frequent in women, reports about the effect of ICV-STZ in female rats are scarce. Our work highlights the need to deepen into the effects of STZ in the female brain and study possible sex differences.
Assuntos
Doença de Alzheimer , Ovariectomia , Estreptozocina , Animais , Feminino , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/metabolismo , Ratos , Injeções Intraventriculares , Ratos Wistar , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Ovário/efeitos dos fármacos , Ovário/metabolismo , Depressão/induzido quimicamente , Depressão/metabolismo , Peptídeos beta-Amiloides/metabolismo , Memória Espacial/efeitos dos fármacosRESUMO
This study aimed to compare the effects of High-Intensity Interval Training (HIIT) performed in a single session(1xHIIT) versus three daily sessions (3xHIIT) on fitness level and behavior of aged rats. Eighteen-month-old Wistar rats were assigned to Untrained (UN), 1xHIIT, or 3xHIIT (n = 12/group). Both groups, 1xHIIT and 3xHIIT, performed 15 min of a treadmill running HIIT protocol during 8 weeks. 1xHIIT protocol consisted of a single daily session of 15 min, while the 3xHIIT performed three daily sessions of 5 min with a 4 h interval between the sessions. Morris Water Maze (MWM) task was used to evaluate spatial learning and memory. Splash test, Forced Swim test, and Elevated Plus Maze task (EPM) were used to evaluate anhedonic, depressive-like, and anxious behaviors, respectively. Rats were euthanized, and the hippocampus was harvested for western blot analyses (CaMKII and BDNF). Both HIIT protocols improved VO2max and spatial memory. Notably, only the 3xHIIT protocol attenuated anxious and depressive-like behaviors. Western blot analyses of the hippocampus revealed that both HIIT protocols increased BDNF levels. BDNF levels were higher in the 3xHIIT when compared with 1xHIIT group, and we observed increasement of the CamKII levels just in the 3x HIIT group. Therefore, this study provides evidence indicating that accumulated HIIT sessions is more effective than traditional daily HIIT sessions in improving fitness level, cognitive function, memory, inhibiting the development of mood disorders, and enhancing BDNF and CaMKII levels in the hippocampus of aged rats.
Assuntos
Envelhecimento , Ansiedade , Fator Neurotrófico Derivado do Encéfalo , Depressão , Treinamento Intervalado de Alta Intensidade , Hipocampo , Ratos Wistar , Animais , Hipocampo/metabolismo , Ratos , Depressão/metabolismo , Depressão/terapia , Depressão/fisiopatologia , Envelhecimento/fisiologia , Envelhecimento/metabolismo , Ansiedade/metabolismo , Ansiedade/terapia , Ansiedade/fisiopatologia , Treinamento Intervalado de Alta Intensidade/métodos , Masculino , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Cognição/fisiologia , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Aprendizagem em Labirinto/fisiologia , Condicionamento Físico Animal/fisiologia , Memória Espacial/fisiologiaRESUMO
Background: Previous work from our group has shown that chronic exposure to Vanadium pentoxide (V2O5) causes cytoskeletal alterations suggesting that V2O5 can interact with cytoskeletal proteins through polymerization and tyrosine phosphatases inhibition, causing Alzheimer's disease (AD)-like hippocampal cell death. Objective: This work aims to characterize an innovative AD experimental model through chronic V2O5 inhalation, analyzing the spatial memory alterations and the presence of neurofibrillary tangles (NFTs), amyloid-ß (Aß) senile plaques, cerebral amyloid angiopathy, and dendritic spine loss in AD-related brain structures. Methods: 20 male Wistar rats were divided into control (deionized water) and experimental (0.02âM V2O5 1âh, 3/week for 6 months) groups (nâ=â10). The T-maze test was used to assess spatial memory once a month. After 6 months, histological alterations of the frontal and entorhinal cortices, CA1, subiculum, and amygdala were analyzed by performing Congo red, Bielschowsky, and Golgi impregnation. Results: Cognitive results in the T-maze showed memory impairment from the third month of V2O5 inhalation. We also noted NFTs, Aß plaque accumulation in the vascular endothelium and pyramidal neurons, dendritic spine, and neuronal loss in all the analyzed structures, CA1 being the most affected. Conclusions: This model characterizes neurodegenerative changes specific to AD. Our model is compatible with Braak AD stage IV, which represents a moment where it is feasible to propose therapies that have a positive impact on stopping neuronal damage.
Assuntos
Doença de Alzheimer , Encéfalo , Modelos Animais de Doenças , Memória Espacial , Compostos de Vanádio , Animais , Masculino , Administração por Inalação , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/patologia , Tonsila do Cerebelo/efeitos dos fármacos , Tonsila do Cerebelo/patologia , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Região CA1 Hipocampal/efeitos dos fármacos , Região CA1 Hipocampal/patologia , Angiopatia Amiloide Cerebral/induzido quimicamente , Angiopatia Amiloide Cerebral/patologia , Espinhas Dendríticas/efeitos dos fármacos , Espinhas Dendríticas/patologia , Córtex Entorrinal/efeitos dos fármacos , Córtex Entorrinal/patologia , Lobo Frontal/efeitos dos fármacos , Lobo Frontal/patologia , Aprendizagem em Labirinto/efeitos dos fármacos , Emaranhados Neurofibrilares/efeitos dos fármacos , Emaranhados Neurofibrilares/patologia , Placa Amiloide/induzido quimicamente , Placa Amiloide/patologia , Ratos Wistar , Memória Espacial/efeitos dos fármacos , Compostos de Vanádio/administração & dosagem , Compostos de Vanádio/toxicidadeRESUMO
Alzheimer's disease is the most common neurodegenerative disease, and its treatment is lacking. In this work, we tested Amylovis-201, a naphthalene-derived compound, as a possible therapeutic candidate for the treatment of AD. For this purpose, we performed three experiments. In the first and third experiment, animals received a bilateral administration of streptozotocin and, starting 24 h after injection, a daily dose of Amylovis-201 (orally), for 17 days or for the whole time of the experiment respectively (28 days), after which learning and memory, as well as the number of hippocampal dentate gyrus cells, were assessed. In the second experiment, healthy animals received a single dose of Amylovis-201, 10 min or 5 h after the learning section to assess whether this substance could promote specific mechanisms involved in memory trace formation. Our data show that, administration of a single dose of Amylovis-201, 10 min after the end of training, but not at 5 h, produces a prolongation in memory duration, probably because it modulates specific mechanisms involved in memory trace consolidation. Furthermore, daily administration of Amylovis-201 to animals with bilateral intracerebroventricular injection of STZ produces a reduction in the loss of the hippocampus dentate gyrus cells and an improvement in spatial memory, probably because Amylovis-201 can interact with some of the protein kinases of the insulin signaling cascade, also involved in neural plasticity, and thereby halt or reverse some of the effects of STZ. Taking to account these results, Amylovis-201 is a good candidate for the therapeutic treatment of AD.
Assuntos
Doença de Alzheimer , Doenças Neurodegenerativas , Animais , Estreptozocina/farmacologia , Doenças Neurodegenerativas/metabolismo , Modelos Animais de Doenças , Hipocampo/metabolismo , Memória Espacial , Transtornos da Memória/metabolismo , Aprendizagem em LabirintoRESUMO
High-fat diet-induced metabolic changes are not restricted to the onset of cardiovascular diseases, but also include effects on brain functions related to learning and memory. This study aimed to evaluate mitochondrial markers and function, as well as cognitive function, in a rat model of metabolic dysfunction. Eight-week-old male Wistar rats were subjected to either a control diet or a two-hit protocol combining a high fat diet (HFD) with the nitric oxide synthase inhibitor L-NAME in the drinking water. HFD plus L-NAME induced obesity, hypertension, and increased serum cholesterol. These rats exhibited bioenergetic dysfunction in the hippocampus, characterized by decreased oxygen (O2) consumption related to ATP production, with no changes in H2O2 production. Furthermore, OPA1 protein expression was upregulated in the hippocampus of HFD + L-NAME rats, with no alterations in other morphology-related proteins. Consistently, HFD + L-NAME rats showed disruption of performance in the Morris Water Maze Reference Memory test. The neocortex did not exhibit either bioenergetic changes or alterations in H2O2 production. Calcium uptake rate and retention capacity in the neocortex of HFD + L-NAME rats were not altered. Our results indicate that hippocampal mitochondrial bioenergetic function is disturbed in rats exposed to a HFD plus L-NAME, thus disrupting spatial learning, whereas neocortical function remains unaffected.
Assuntos
Dieta Hiperlipídica , Memória Espacial , Ratos , Animais , Masculino , Dieta Hiperlipídica/efeitos adversos , Ratos Wistar , NG-Nitroarginina Metil Éster/farmacologia , NG-Nitroarginina Metil Éster/metabolismo , Peróxido de Hidrogênio/metabolismo , Aprendizagem em Labirinto , Hipocampo/metabolismo , Mitocôndrias/metabolismoRESUMO
Spatial learning is a complex cognitive skill and ecologically important trait scarcely studied in crustaceans. We investigated the ability of the Pacific (Ecuadorian) hermit crab Coenobita compressus, to learn an allocentric spatial task using a palatable novel food as reward. Crabs were trained to locate the reward in a single session of eleven consecutive trials and tested subsequently, for short- (5 min) and long-term memory 1, 3 and 7 days later. Our results indicate that crabs were able to learn the location of the reward as they showed a reduction in the time required to find the food whenever it was present, suggesting a visuo-spatial and olfactory cue-guided task resolution. Moreover, crabs also remember the location of the reward up to 7 days after training using spatial cues only (without the food), as evidenced by the longer investigation time they spent in the learned food location than in any other part of the experimental arena, suggesting a visuo-spatial memory formation. This study represents the first description of allocentric spatial long-term memory in a terrestrial hermit crab.
Assuntos
Anomuros , Animais , Memória Espacial , Olfato , Sinais (Psicologia) , AlimentosRESUMO
The cognitive effects of nicotine are linked to persistent modifications in extended neural systems that regulate cognitive and emotional processes, and these changes occur during development. Additionally, acute stress has modulatory effects on cognition that involve broad neural systems and can be influenced by prior environmental challenges. The effects of nicotine and stress may be interconnected, leading to modifications in a network of shared brain substrates. Here, we explored the interaction between nicotine and stress by evaluating the effects of acute stress exposure in spatial memory retrieval for animals pretreated with nicotine during adolescence or adulthood. Adolescent (35 days old) and adult (70 days old) male Wistar rats were treated for 21 days with one daily subcutaneous injection of nicotine 0.14 mg/ml (free base). 30 days after the last injection, rats were trained in the Barnes maze and tested 24 h later, half the rats were tested under regular conditions, and half of them were exposed to 1 h of restraining stress before the retrieval test, and brain samples were collected and c-Fos immunopositive cells were stained. Prolonged nicotine withdrawal or acute stress improved spatial memory retrieval. Acute stress in nicotine pretreated adults impaired spatial memory retrieval. Nicotine exposure during early adulthood resulted in long-lasting brain adaptations that amplified emotional responses to acute stress after prolonged drug withdrawal.
Assuntos
Nicotina , Síndrome de Abstinência a Substâncias , Ratos , Masculino , Animais , Nicotina/farmacologia , Memória Espacial , Ratos Wistar , Encéfalo/metabolismo , Síndrome de Abstinência a Substâncias/metabolismoRESUMO
Locating food in heterogeneous environments is a core survival challenge. The distribution of resources shapes foraging strategies, imposing demands on perception, learning and memory, and associated brain structures. Indeed, selection for foraging efficiency is linked to brain expansion in diverse taxa, from primates1 to Hymenopterans2. Among butterflies, Heliconius have a unique dietary adaptation, actively collecting and feeding on pollen, providing a source of essential amino acids as adults, negating reproductive senescence and facilitating an extended longevity3. Several lines of evidence suggest that Heliconius learn the spatial location of pollen resources within an individual's home range4, and spatial learning may be more pronounced at these large spatial scales. However, experimental evidence of spatial learning in Heliconius, or any other butterfly, is so far absent. We therefore tested the ability of Heliconius to learn the spatial location of food rewards at three ecologically-relevant spatial scales, representing multiple flowers on a single plant, multiple plants within a locality, and multiple localities. Heliconius were able to learn spatial information at all three scales, consistent with this ability being an important component of their natural foraging behaviour.
Assuntos
Borboletas , Animais , Memória Espacial , Dieta , Pólen , AlimentosRESUMO
Early-life adversity, like perinatal protein malnutrition, increases the vulnerability to develop long-term alterations in brain structures and function. This study aimed to determine whether perinatal protein malnutrition predisposes to premature aging in a murine model and to assess the cellular and molecular mechanisms involved. To this end, mouse dams were fed either with a normal (NP, casein 20%) or a low-protein diet (LP, casein 8%) during gestation and lactation. Female offspring were evaluated at 2, 7 and 12 months of age. Positron emission tomography analysis showed alterations in the hippocampal CA3 region and the accessory olfactory bulb of LP mice during aging. Protein malnutrition impaired spatial memory, coinciding with higher levels of reactive oxygen species in the hippocampus and sirt7 upregulation. Protein malnutrition also led to higher senescence-associated ß-galactosidase activity and p21 expression. LP-12-month-old mice showed a higher number of newborn neurons that did not complete the maturation process. The social-odor discrimination in LP mice was impaired along life. In the olfactory bulb of LP mice, the senescence marker p21 was upregulated, coinciding with a downregulation of Sirt2 and Sirt7. Also, LP-12-month-old mice showed a downregulation of catalase and glutathione peroxidase, and LP-2-month-old mice showed a higher number of newborn neurons in the subventricular zone, which then returned to normal values. Our results show that perinatal protein malnutrition causes long-term impairment in cognitive and olfactory skills through an accelerated senescence phenotype accompanied by an increase in oxidative stress and altered sirtuin expression in the hippocampus and olfactory bulb.
Assuntos
Senilidade Prematura , Desnutrição , Gravidez , Camundongos , Animais , Feminino , Memória Espacial , Senilidade Prematura/genética , Caseínas/metabolismo , Estresse Oxidativo , Transtornos da Memória/etiologia , Bulbo Olfatório/fisiologia , Desnutrição/complicações , Desnutrição/metabolismoRESUMO
Vitamin D3 deficiency is associated with an increased risk of dementia. An association between vitamin D3 deficiency and subjective cognitive complaints in geriatric patients has been previously reported. This study aimed to evaluate the effects of two doses of vitamin D3 on spatial memory (using the Radial Maze) and cytokine levels [tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and interleukin-10 (IL-10)] on 2-, 6-, 13-, 22-, and 31-month-old male Wistar rats. Animals were supplemented with vitamin D3 at doses of 42 IU/kg and 420 IU/kg for 21 days. A radial maze test was performed to evaluate spatial memory. After the behavioral test, the frontal cortex and hippocampus were dissected for enzyme immunoassay analyses to measure the cytokine levels (TNFα, IL-1ß, IL-6, and IL-10). Our results showed that vitamin D3 supplementation reversed spatial memory impairment at the supplemented doses (42 and 420 IU/kg) in 6-, 13-, and 22-month-old animals and at a dose of 420 IU/kg in 31-month-old animals. The lower dose (42 IU/kg) regulates both pro- and anti-inflammatory cytokines mainly in the frontal cortex. Our results suggest that vitamin D3 has a modulatory action on pro- and anti-inflammatory cytokines, since older animals showed increased cytokine levels compared to 2-month-old animals, and that vitamin D3 may exert an immunomodulatory effect on aging.
Assuntos
Colecalciferol , Deficiência de Vitamina D , Ratos , Masculino , Animais , Colecalciferol/farmacologia , Colecalciferol/uso terapêutico , Citocinas , Interleucina-10 , Ratos Wistar , Interleucina-6 , Memória Espacial , Fator de Necrose Tumoral alfa , Anti-InflamatóriosRESUMO
Alzheimer's dementia (AD) is a neurodegenerative disorder that causes memory loss and dementia in older adults. Intracellular accumulation of Aß causes an imbalance in the oxidative status and cognitive dysfunctions. Besides oxidative stress and loss of memory, Alzheimer's patients show dysfunction of the circadian rhythms. The objective of this work was to evaluate the consequences of an intracerebroventricular injection of Aß (1-42) on temporal patterns of cognitive performance, as well as on lipid peroxidation, protein oxidation and total antioxidant capacity levels, in the rat temporal cortex. Holtzman male rats from control and Aß-injected groups were used in this study. We found that MDA, protein carbonyls and total antioxidant capacity levels displayed day-night oscillations in the rat temporal cortex and spatial memory performance also varied rhythmically. An intracerebroventricular injection of Aß (1-42) modified temporal patterns of cognitive performance as well as daily profiles of parameters of oxidative stress. Thus, elevated levels of Aß aggregates induces alterations in daily rhythmicity of parameters of oxidative stress and, consequently, would affect cellular clock activity, affecting the spatial memory performance in the AD.
Assuntos
Doença de Alzheimer , Ratos , Masculino , Animais , Doença de Alzheimer/metabolismo , Antioxidantes/metabolismo , Peptídeos beta-Amiloides/metabolismo , Memória Espacial , Ratos Wistar , Lobo Temporal/metabolismo , Cognição , Estresse Oxidativo , Ratos Sprague-Dawley , Fragmentos de Peptídeos/metabolismo , Modelos Animais de DoençasRESUMO
Research on the memory impairment caused by the Amyloid-ß 25-35 (Aß25-35) peptide in animal models has provided an understanding of the causes that occurs in Alzheimer's disease. However, it is uncertain whether this cognitive impairment occurs due to disruption of information encoding and consolidation or impaired retrieval of stored memory. The aim of this study was to determine the effect of the Aß25-35 peptide on the morphology of dendritic spines and the changes in the expression of NR2B and PSD-95 in the hippocampus associated with learning and memory deficit. Vehicle or Aß25-35 peptide (0.1 µg/µL) was bilaterally administered into the CA1 subfield of the rat hippocampus, then tested for spatial learning and memory in the Morris Water Maze. On Day 39, the morphological changes in the CA1 of the hippocampus and dentate gyrus were examined via Golgi-Cox stain. It was observed that the Aß25-35 peptide administered in the CA1 region of the rat hippocampus induced changes to the morphology of dendritic spines and the expression of the NR2B subunit of the NMDA receptor co-localized with both the spatial memory and PSD-95 protein in the hippocampus of learning rats. We conclude that, in soluble form, the Aß25-35 peptide perturbs synaptic plasticity, specifically in the formation of new synapses, thus promoting the progression of memory impairment.
Assuntos
Doença de Alzheimer , Espinhas Dendríticas , Animais , Ratos , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Espinhas Dendríticas/metabolismo , Proteína 4 Homóloga a Disks-Large/metabolismo , Hipocampo/metabolismo , Aprendizagem em Labirinto , Transtornos da Memória/metabolismo , Fragmentos de Peptídeos/farmacologia , Fragmentos de Peptídeos/metabolismo , Memória EspacialRESUMO
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)
Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Cognição , Maleabilidade , Inibição Psicológica , Memória de Curto Prazo , Percepção , Testes de Aptidão , Jogos e Brinquedos , Ludoterapia , Atenção Primária à Saúde , Resolução de Problemas , Fenômenos Psicológicos , Testes Psicológicos , Psicologia , Rememoração Mental , Recreação , Retenção Psicológica , Atenção , Instituições Acadêmicas , Percepção Auditiva , Ajustamento Social , Apoio Social , Percepção da Fala , Estresse Psicológico , Análise e Desempenho de Tarefas , Tecnologia , Terapêutica , Pensamento , Escalas de Wechsler , Comportamento , Ciências do Comportamento , Neurociências , Adaptação Psicológica , Criança , Cuidado da Criança , Pré-Escolar , Monitoramento Ambiental , Organizações , Saúde da Criança , Dissonância Cognitiva , Estatísticas não Paramétricas , Estado de Consciência , Intuição , Manifestações Neurocomportamentais , Disciplinas e Atividades Comportamentais , Autoeficácia , Criatividade , Reconhecimento Psicológico , Autonomia Pessoal , Acesso à Informação , Compreensão , Crescimento e Desenvolvimento , Discriminação Psicológica , Educação , Emoções , Planejamento , Cérebro , Resiliência Psicológica , Função Executiva , Teste de Stroop , Atenção Plena , Memória Espacial , Autocontrole , Metacognição , Escala de Memória de Wechsler , Testes de Memória e Aprendizagem , Autogestão , Mentalização , Frustração , Revisão Sistemática , Regulação Emocional , Análise de Escalonamento Multidimensional , Autoteste , Estado Funcional , Interação Social , Treino Cognitivo , Velocidade de Processamento , Desenvolvimento Psicológico , Atividade Nervosa Superior , Atividades Humanas , Imaginação , Desenvolvimento da Linguagem , Transtornos do Desenvolvimento da Linguagem , Aprendizagem , Processos Mentais , Atividade Motora , Testes Neuropsicológicos , NeuropsicologiaRESUMO
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)
Assuntos
Humanos , Masculino , Feminino , Isolamento Social , Sistemas On-Line , Consulta Remota , Cultura , Intervenção Baseada em Internet , História , Neuropsicologia , Relações Pais-Filho , Testes de Aptidão , Prática Psicológica , Resolução de Problemas , Testes Psicológicos , Psicologia , Qualidade de Vida , Atenção , Transtorno do Deficit de Atenção com Hiperatividade , Escalas de Wechsler , Comportamento , Inclusão Escolar , Adaptação Psicológica , Família , Criança , Desenvolvimento Infantil , Linguagem Infantil , Pré-Escolar , Poder Familiar , Cognição , Infecções por Coronavirus , Comunicação , Educação Baseada em Competências , Complacência (Medida de Distensibilidade) , Intervenção Educacional Precoce , Manifestações Neurocomportamentais , Reconhecimento Psicológico , Demência , Crescimento e Desenvolvimento , Comunicação por Videoconferência , Avaliação de Programas e Instrumentos de Pesquisa , Cérebro , Estudos Interdisciplinares , Memória Espacial , Transtornos do Neurodesenvolvimento , Escala de Avaliação Comportamental , Questionário de Saúde do Paciente , Testes de Memória e Aprendizagem , Testes de Estado Mental e Demência , Lobo Frontal , Egocentrismo , Raciocínio Clínico , COVID-19 , Treino Cognitivo , Apoio Familiar , Desenvolvimento Humano , Serviços de Informação , Testes de Inteligência , Desenvolvimento da Linguagem , Memória , Memória de Curto Prazo , Processos Mentais , Exame Neurológico , Plasticidade Neuronal , Testes NeuropsicológicosRESUMO
AIMS: The accumulated evidence suggests that lifestyle - specifically dietary habits and stress exposure - plays a detrimental role in health. The purpose of the present study was to analyze the interplay of stress, diet, and sex in metabolic and cognitive alterations. MAIN METHODS: For this purpose, one-month-old C57Bl/6J mice were fed with a standard diet or high-fat diet (HFD). After eight weeks, one subgroup of mice from each respective diet was exposed to 20 weeks of chronic mild stress (CMS), whilst the others were left undisturbed. KEY FINDINGS: After 28 weeks of HFD feeding, mice from both sexes were overweight, with an increase in caloric intake and abdominal and subcutaneous fat pads. Stress exposure induced a decrease in body weight, related to a decrease in caloric efficiency in both males and females. Results indicate that males are more susceptible than the females in modulating metabolic and cognitive functions under HFD and CMS. Although both sexes demonstrated HFD-induced weight gain, fat accumulation, insulin resistance, high cholesterol, only males exposed to CMS but not females have (i) impaired glucose tolerance with higher glucose level; (ii) significant prolonged latency in Barnes test, suggesting cognitive impairment; (iii) increased IFN-gamma expression in hippocampus, suggesting greater neuroinflammatory response; (iv) poorer cognitive performance related to a decrease in hippocampal and spleen BDNF mRNA expression. SIGNIFICANCE: The main finding in this study is the presence of a sexual dimorphism in modulating metabolic and cognitive functions under HFD and CMS, showing males are more susceptible than females. In addition, poorer cognitive performance was related to a decrease in hippocampal BDNF mRNA expression. Interestingly, these changes were observed in the spleen as well.
Assuntos
Dieta Hiperlipídica , Caracteres Sexuais , Memória Espacial , Animais , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Colesterol/metabolismo , Cognição , Dieta Hiperlipídica/efeitos adversos , Feminino , Glucose/metabolismo , Hipocampo/metabolismo , Masculino , Transtornos da Memória/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Baço/metabolismoRESUMO
Obesity is characterized by excessive fat accumulation. The Zucker rat displays genetic obesity due to a mutation in the leptin receptor gene; this model is of great interest because of its similarity to human obesity. Brain regions may be affected by obesity, but detailed information is lacking. In the present study, we analyzed the morphology of neurons in the hippocampal trisynaptic circuit as well as the spatial memory of obese Zucker rats. We performed two experiments. Each experiment contained two experimental groups: the control group (male Long Evans rats) and the study group (obese male Zucker rats). We monitored the body weights of all rats over 4 weeks. In the first experiment, we analyzed the morphology of hippocampal neurons. Under anesthesia, we measured the abdominal and hip circumferences and collected at least 1 ml of blood to assess serum glucose (GLU), triglyceride (TGC), and cholesterol (COL) concentrations. We perfused the brains of these rats with 0.9% saline solution, incubated the brains in Golgi-Cox solution, and subsequently evaluated the morphology of pyramidal neurons in the hippocampus (the CA1-CA3 regions) and the entorhinal cortex as well as the morphology of granule neurons in the dentate gyrus. In the second experiment, we assessed the spatial memory of animals with the Morris water maze. The Zucker rats had an obese phenotype, as indicated by their elevated body weight and increased abdominal and hip circumferences as well as elevated GLU, COL, and TGC concentrations. Analysis of neurons from the specified regions in obese male Zucker rats indicated reduced dendritic arborization and reduced dendritic spine density. In terms of spatial learning and memory, the obese Zucker rats exhibited intact spatial learning (i.e., of platform location) but deficits in spatial memory. These data provide evidence that obesity alters the morphology and function of hippocampal neurons.
Assuntos
Hipocampo , Memória Espacial , Humanos , Masculino , Ratos , Animais , Memória Espacial/fisiologia , Ratos Zucker , Ratos Long-Evans , Neurônios/fisiologia , Transtornos da Memória/etiologia , Plasticidade Neuronal , ObesidadeRESUMO
In humans and rats, aging is associated with a progressive deterioration of spatial learning and memory. These functional alterations are correlated with morphological and molecular changes in the hippocampus. Here, we assessed age-related changes in DNA methylation (DNAm) landscape in the rat hippocampus and the correlation of spatial memory with hippocampal DNAm age in 2.6- and 26.6-month-old rats. Spatial memory performance was assessed with the Barnes maze test. To evaluate learning ability and spatial memory retention, we assessed the time spent by animals in goal sector 1 (GS1) and 3 (GS3) when the escape box was removed. The rat pan-tissue clock was applied to DNAm data from hippocampal tissue. An enrichment pathway analysis revealed that neuron fate commitment, brain development, and central nervous system development were processes whose underlying genes were enriched in hypermethylated CpGs in the old rats. In the old rat hippocampi, the methylation levels of CpG proximal to transcription factors associated with genes Pax5, Lbx1, Nr2f2, Hnf1b, Zic1, Zic4, Hoxd9; Hoxd10, Gli3, Gsx1 and Lmx1b, and Nipbl showed a significant regression with spatial memory performance. Regression analysis of different memory performance indices with hippocampal DNAm age was significant. These results suggest that age-related hypermethylation of transcription factors related to certain gene families, such as Zic and Gli, may play a causal role in the decline in spatial memory in old rats. Hippocampal DNAm age seems to be a reliable index of spatial memory performance in young and old rats.
Assuntos
Metilação de DNA , Memória Espacial , Animais , Ratos , Envelhecimento/genética , Proteínas de Ciclo Celular/genética , Epigênese Genética , Hipocampo , Aprendizagem em Labirinto/fisiologia , Memória Espacial/fisiologia , Fatores de Transcrição/genéticaRESUMO
Exposure to stressors in early postnatal life induces long-lasting modifications in brain function. This plasticity, an essential characteristic of the brain that enables adaptation to the environment, may also induce impairments in some psychophysiological functions, including learning and memory. Early life stress (ELS) has long-term effects on the hypothalamic-pituitary-adrenal axis response to stressors, and has been reported to lead to neuroinflammation, altered levels of neurotrophic factors, modifications in neurogenesis and synaptic plasticity, with changes in neurotransmitter systems and network functioning. In this review, we focus on early postnatal stress in animal models and their effects on learning and memory. Many studies have reported ELS-induced impairments in different types of memories, including spatial memory, fear memory, recognition (both for objects and social) memory, working memory and reversal learning. Studies are not always in agreement, however, no effects, or sometimes facilitation, being reported, depending on the nature and intensity of the early intervention, as well as the age when the outcome was evaluated and the sex of the animals. When considering processes occurring after consolidation, related with memory maintenance/persistence or transformation, there are a very reduced number of reports. Future studies addressing the mechanisms underlying memory changes for ELS should shed some light on the understanding of the different effects induced by stressors of different types and intensities on cognitive functions.