RESUMO
The beneficial effects of increasing histamine levels on memory have acquired special interest due to their applicability to psychiatric conditions that cause memory impairments. In addition, by employing drug repurposing approaches, it was demonstrated that dihydroergotamine (DHE), an FDA drug approved to treat migraines, inhibits Histamine N Methyl Transferase (HNMT), the enzyme responsible for the inactivation of histamine in the brain. For this reason, in the present work, the effect of DHE on histamine levels in the hippocampus and its effects on memory was evaluated, employing the scopolamine-induced amnesia model, the Novel Object Recognition (NOR) paradigm, and the Morris Water Maze (MWM). Furthermore, the role of histamine 1 receptor (H1R) and histamine 2 receptor (H2R) antagonists in the improvement in memory produced by DHE in the scopolamine-induced amnesia model was evaluated. Results showed that the rats that received DHE (10 mg/kg, i.p.) showed increased histamine levels in the hippocampus after 1 h of administration but not after 5 h. In behavioral assays, it was shown that DHE (1 mg/kg, i.p.) administered 20 min before the training reversed the memory impairment produced by the administration of scopolamine (2 mg/kg, i.p.) immediately after the training in the NOR paradigm and MWM. Additionally, the effects in memory produced by DHE were blocked by pre-treatment with pyrilamine (20 mg/kg, i.p.) administered 30 min before the training in the NOR paradigm and MWM. These findings allow us to demonstrate that DHE improves memory in a scopolamine-induced amnesia model through increasing histamine levels at the hippocampus due to its activity as an HNMT inhibitor.
Assuntos
Di-Hidroergotamina , Escopolamina , Animais , Ratos , Histamina , Amnésia/induzido quimicamente , Amnésia/tratamento farmacológico , Encéfalo , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Antagonistas dos Receptores H2 da HistaminaRESUMO
Corticosterone (CORT) release during learning experiences is associated with strong memories and activity of the glucocorticoid receptor. It has been shown that lesions of the dorsal striatum (DS) of rats trained in the cued version of the Morris water maze impair memory, and that local injection of CORT improves its performance, suggesting that DS activity is involved in procedural memory which may be modulated by CORT. We trained rats in cued Morris water maze and analyzed the effect of CORT synthesis inhibition on performance, CORT levels, expression of plasticity-involved genes, such as the brain derived neurotrophic factor (BDNF), casein kinase 2 (CK2), and the serum/glucocorticoid regulated kinase 1 (SGK1), as well as the presence of phosphorylated nuclear glucocorticoid receptor in serine 232 (pGR-S232) in the DS. The inhibition of CORT synthesis by metyrapone reduced CORT levels in plasma, prevented its increment in DS and impaired the performance of cued water maze. Additionally, there was an increase of CK2 and SGK1 mRNAs expression in trained subjects, which was unrelated to CORT levels. Finally, we did not observe changes in nuclear pGR-S232 in any condition. Our findings agree with evidence demonstrating that decreasing CORT levels hinders acquisition and consolidation of the spatial version of the Morris water maze; these novel findings broaden our knowledge about the involvement of the DS in the mechanisms underlying procedural memory.
RESUMO
BACKGROUND: The application of automated analyses in neuroscience has become a practical approach. With automation, the algorithms and tools employed perform fast and accurate data analysis. It minimizes the inherent errors of manual analysis performed by a human experimenter. It also reduces the time required to analyze a large amount of data and the need for human and financial resources. METHODS: In this work, we describe a protocol for the automated analysis of the Morris Water Maze (MWM) and the Open Field (OF) test using the OpenCV library in Python. This simple protocol tracks mice navigation with high accuracy. RESULTS: In the MWM, both automated and manual analysis revealed similar results regarding the time the mice stayed in the target quadrant (p = 0.109). In the OF test, both automated and manual analysis revealed similar results regarding the time the mice stayed in the center (p = 0.520) and in the border (p = 0.503) of the field. CONCLUSIONS: The automated analysis protocol has several advantages over manual analysis. It saves time, reduces human errors, can be customized, and provides more consistent information about animal behavior during tests. We conclude that the automated protocol described here is reliable and provides consistent behavioral analysis in mice. This automated protocol could lead to deeper insight into behavioral neuroscience.
Assuntos
Algoritmos , Software , Humanos , Camundongos , Animais , Comportamento AnimalRESUMO
Morris water maze (MWM) test is widely used to evaluate the learning and memory deficits in rodents. Image processing and pattern recognition can be used to analyse videos and recognize automatically the tracking in MWM. There are several commercial and free access software that allows analyzing the behavioral tasks although they also have limitations such as automation, cost, user intervention among other things. The aim of this paper was to develop a new image processing technique to automatically analyse the track of the rat in the MWM, which we called RatsTrack. The MWM test was performed with an animal model for Alzheimer, and the videos were recorded to measure the distance, time, and speed. The segmentation method based on the projection of the video frames was made for pool identification, eliminating the rat, while conserving the shape of the pool. Then, the Hough transformation was used to recognize the position and radius of the pool. Finally, the frame in which the rat is released into the pool was established automatically using mathematical morphology techniques and added as a plugin on free access ImageJ software. The new image processing technique, RatsTrack, successfully detected and located the pool and rat without user intervention, significantly decreasing operational time and providing results for distance, time, speed, and acceleration parameters of the MWM test. Alzheimer's rats compared with the control group presented significant data measured with the RatsTrack. RatsTrack is a plugin of ImageJ software and will be made freely available for public use.
RESUMO
The prevalence of autism spectrum disorder (ASD), a neurodevelopmental condition that impacts social interaction and sensory processing, is rising. Valproic acid (VPA) exposure during pregnancy causes autistic-like traits in offspring. Olanzapine (OLZ), an atypical antipsychotic, is used to treat ASD. We assessed the impact of OLZ on behavior, neuromorphology, and nitric oxide (NO) levels in the hippocampus using prenatal VPA treatment in rats. It is commonly known that ASD patients exhibit sensory abnormalities. As such, we utilized the tail flick test to validate the ASD model. In the novel object recognition test (NORT), VPA exposure reduces the discrimination index (DI) in the first introduction to the novel object. Moreover, OLZ and vehicle-treated rats perform differently in the second exposition to the DI of the novel object, suggesting that OLZ reverses VPA-induced deficits in recognition memory. The latency to find the hidden platform in the Morris water maze test of memory and learning improves in VPA-exposed rats after OLZ administration, indicating that OLZ improves spatial memory in these rats. Administration of prenatal VPA induces neuronal hypotrophy and reduces spine density in pyramidal neurons of the CA1 region of the hippocampus. Treatment with OLZ corrects the neuromorphological changes brought on by VPA. In the CA1 region of the hippocampus, VPA treatment increases the number of neurons, which normalizes with OLZ treatment. OLZ increases the NO levels in the dorsal hippocampus in control rats. In rats exposed to VPA, the second-generation antipsychotic OLZ reduces memory-related and neuroplastic alterations. The current findings support the use of OLZ in this illness and further validate the use of prenatal VPA as a model of ASD.
Assuntos
Antipsicóticos , Transtorno do Espectro Autista , Transtorno Autístico , Efeitos Tardios da Exposição Pré-Natal , Gravidez , Feminino , Ratos , Masculino , Animais , Humanos , Transtorno Autístico/induzido quimicamente , Transtorno Autístico/tratamento farmacológico , Antipsicóticos/farmacologia , Antipsicóticos/uso terapêutico , Olanzapina/efeitos adversos , Transtorno do Espectro Autista/induzido quimicamente , Ácido Valproico/farmacologia , Ácido Valproico/uso terapêutico , Neurônios , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Modelos Animais de Doenças , Efeitos Tardios da Exposição Pré-Natal/tratamento farmacológico , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Comportamento Animal , Comportamento SocialRESUMO
Introduction: Neuronal Ca2+ signals generated through the activation of Ca2+-induced Ca2+ release in response to activity-generated Ca2+ influx play a significant role in hippocampal synaptic plasticity, spatial learning, and memory. We and others have previously reported that diverse stimulation protocols, or different memory-inducing procedures, enhance the expression of endoplasmic reticulum-resident Ca2+ release channels in rat primary hippocampal neuronal cells or hippocampal tissue. Methods and Results: Here, we report that induction of long-term potentiation (LTP) by Theta burst stimulation protocols of the CA3-CA1 hippocampal synapse increased the mRNA and protein levels of type-2 Ryanodine Receptor (RyR2) Ca2+ release channels in rat hippocampal slices. Suppression of RyR channel activity (1 h preincubation with 20 µM ryanodine) abolished both LTP induction and the enhanced expression of these channels; it also promoted an increase in the surface expression of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits GluR1 and GluR2 and caused a moderate but significant reduction of dendritic spine density. In addition, training rats in the Morris water maze induced memory consolidation, which lasted for several days after the end of the training period, accompanied by an increase in the mRNA levels and the protein content of the RyR2 channel isoform. Discussion: We confirm in this work that LTP induction by TBS protocols requires functional RyR channels. We propose that the increments in the protein content of RyR2 Ca2+ release channels, induced by LTP or spatial memory training, play a significant role in hippocampal synaptic plasticity and spatial memory consolidation.
RESUMO
Here, we investigate the effects of obesity induced by monosodium glutamate (MSG) on cognitive impairment and whether this model induces any alteration in the affinity, density, and subtypes of muscarinic acetylcholine receptors (mAChRs) in rat hippocampus. Healthy rats were used as controls, and MSG-obese rats were selected via the Lee index > 0.300. The effects of MSG-induced obesity on hippocampal spatial learning and memory processes were evaluated by using the working memory versions of the Morris’ water maze task and the evaluation of mAChRs by binding assay and their subtypes by immunoprecipitation assays. [3H]Quinuclidinyl benzilate specific binding analysis showed that the equilibrium dissociation constant (KD) did not differ between control and MSG, indicating that affinity is not affected by obesity induced by MSG. The maximum number of binding sites (Bmax) obtained in MSG subjects was lower than that obtained from control rats, indicating a decrease in the expression of total mAChRs. Immunoprecipitation assays reveal a decrease in the expression of M1 subtype of MSG when compared with control rats (M2 to M5 subtypes did not differ between control and MSG). We also observed that MSG promotes a disruption of the spatial working memory which was accompanied by a decrease in the M1 mAChR subtype in rat hippocampus, thus suggesting deleterious long-term effects besides the obesity. In conclusion, these findings provide new insights into how obesity can influence spatial learning and memory that is hippocampal-dependent. The data suggest that the M1 mAChR subtype protein expression is a potential therapeutic target.
RESUMO
Memory is the ability to store, retrieve and use information that requires a progressive time-dependent stabilization process known as consolidation to be established. The hippocampus is essential for processing all the information that forms memory, especially spatial memory. Neuropeptide Y (NPY) affects memory, so in this study we investigated the participation and recruitment of NPY receptors during spatial memory consolidation in rats. Using the water maze test, we show that NPY (1 pmol) injected into the dorsal hippocampus impaired memory consolidation and that previous restraint stress (30 min) potentiates NPY effects, i.e. further impaired memory consolidation. Using selective antagonists for NPY Y1 and Y2 receptors we demonstrate that both receptors play a key role on spatial memory consolidation. Our data suggest that NPY modulates aversive and adaptive memory formation by NPY receptors activation.
Assuntos
Comportamento Animal/fisiologia , Transtornos da Memória/metabolismo , Neuropeptídeo Y/metabolismo , Receptores de Neuropeptídeo Y/metabolismo , Memória Espacial/fisiologia , Estresse Psicológico/metabolismo , Animais , Arginina/análogos & derivados , Arginina/farmacologia , Comportamento Animal/efeitos dos fármacos , Benzazepinas/farmacologia , Modelos Animais de Doenças , Masculino , Ratos , Ratos Wistar , Receptores de Neuropeptídeo Y/antagonistas & inibidores , Restrição FísicaRESUMO
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.
Assuntos
Colecalciferol/análise , Óxido Nítrico/efeitos adversos , Encefalopatias/patologia , Doenças Desmielinizantes/classificação , Etídio/efeitos adversos , Memória Espacial/classificação , Teste do Labirinto Aquático de MorrisRESUMO
Object recognition (OR) and the Morris water maze (MWM) are classical tasks widely used to assess memory parameters and deficits in rodents. Learning processes in both tasks involve integrity of the hippocampus and associated regions, and prefrontal cortex connections. Here, we highlight the idea that these classical tests can be used to indicate memory deficits caused by models of disease that affect hippocampal function in rats, and identify some practical issues of OR and MWM, based on the literature and our experience. Additionally, we have shown that the performance of both tasks does not alter blood levels of corticosterone, considering exposure to a single task. Hence, taking into consideration the difficulties and care required during task execution, the infrastructure needed and the training of the experimenter, we suggest that OR and its variations offer minimal manageable stressful conditions, representing an effective and practical tool for hippocampal-related memory assessment of rats. Thus, OR may provide similar information to that of the MWM, despite controversy regarding hippocampus participation in OR and given due differences in the types of memory evaluated and researchers' objectives. We recommend the observation of some important precautions and details, also based on the literature and our own experience.
Assuntos
Disfunção Cognitiva/diagnóstico , Hipocampo/metabolismo , Teste do Labirinto Aquático de Morris , Reconhecimento Psicológico , Animais , Comportamento Animal , Disfunção Cognitiva/metabolismo , Corticosterona/sangue , Hipocampo/lesões , Masculino , Transtornos da Memória/diagnóstico , Ratos , Ratos Wistar , Percepção VisualRESUMO
ABSTRACT Purpose: To explore the role and mechanisms of octreotide in neurofunctional recovery in the traumatic brain injury (TBI) model. Methods: Rats were subjected to midline incision followed by TBI in the prefrontal cortex region. After 72 hours, the behavioural and neurological deficits tests were performed, which included memory testing on Morris water maze for 5 days. Octreotide (15 and 30 mg/kg i.p.) was administered 30 minutes before subjecting to TBI, and its administration was continued for three days. Results: In TBI-subjected rats, administration of octreotide restored on day 4 escape latency time (ELT) and increased the time spent in the target quadrant (TSTQ) on day 5, suggesting the improvement in learning and memory. It also increased the expression of H2S, Nrf2, and cystathionine-γ-lyase (CSE) in the prefrontal cortex, without any significant effect on cystathionine-β-synthase. Octreotide also decreased the TNF-α levels and neurological severity score. However, co-administration of CSE inhibitor (D,L-propargylglycine) abolished octreotide-mediated neurofunctional recovery, decreased the levels of H2S and Nrf2 and increased the levels of TNF-α. Conclusions: Octreotide improved the neurological functions in TBI-subjected rats, which may be due to up-regulation of H2S biosynthetic enzyme (CSE), levels of H2S and Nrf2 and down-regulation of neuroinflammation.
Assuntos
Animais , Ratos , Octreotida/farmacologia , Lesões Encefálicas Traumáticas/tratamento farmacológico , Sulfeto de Hidrogênio/metabolismo , Sulfeto de Hidrogênio/farmacologia , Fator de Necrose Tumoral alfa , Fator 2 Relacionado a NF-E2RESUMO
BACKGROUND: Alzheimer's disease (AD) is a chronic, progressive neurodegenerative disease. Recent studies have reported the close association between cognitive function in AD and purinergic receptors in the central nervous system. In the current study, we investigated the effect of CD73 inhibitor α, ß-methylene ADP (APCP) on cognitive impairment of AD in mice, and to explore the potential underlying mechanisms. RESULTS: We found that acute administration of Aß142 (i.c.v.) resulted in a significant increase in adenosine release by using microdialysis study. Chronic administration of APCP (10, 30 mg/kg) for 20 d obviously mitigated the spatial working memory impairment of Aß142-treated mice in both Morris water maze (MWM) test and Y-maze test. In addition, the extracellular adenosine production in the hippocampus was inhibited by APCP in Aß-treated mice. Further analyses indicated expression of acetyltransferase (ChAT) in hippocampus of mice of was significantly reduced, while acetylcholinesterase (AChE) expression increased, which compared to model group. We observed that APCP did not significantly alter the NLRP3 inflammasome activity in hippocampus, indicating that anti-central inflammation seems not to be involved in APCP effect. CONCLUSIONS: In conclusion, we report for the first time that inhibition of CD73 by APCP was able to protect against memory loss induced by Aß142 in mice, which may be due to the decrease of CD73-driven adenosine production in hippocampus. Enhancement of central cholinergic function of the central nervous system may also be involved in the effects of APCP.
Assuntos
Animais , Masculino , Camundongos , Difosfato de Adenosina/análogos & derivados , Doenças Neurodegenerativas/prevenção & controle , Hipocampo , Nucleotidases/antagonistas & inibidores , Acetilcolinesterase , Difosfato de Adenosina/administração & dosagem , Doença de Alzheimer/prevenção & controle , Teste do Labirinto Aquático de Morris , Camundongos Endogâmicos C57BLRESUMO
Spatial learning and memory enables individuals to orientate themselves in an external environment. Synaptic stimulation of dendritic spines on hippocampal place cells underlies adaptive cognitive performance, inducing plastic changes such as spinogenesis, pruning and structural interconversion. Such plastic changes are driven by complex molecular machinery that relies on several actin cytoskeleton-associated proteins (ACAP's), these interacting with actin filaments in the postsynaptic density to guide the conformational changes to spines in accordance with the synaptic information they receive. However, the specific dynamics of the plastic changes in spines driven by ACAP's are poorly understood. Adult rats exhibit efficient allocentric reference memory 30 days after training in a spatial learning paradigm in the Morris water maze. A Golgi study revealed this behavior to be associated with a reduction in both spine density and in mushroom spines, as well as a concomitant increase in thin spines. These changes were accompanied by the overexpression of mRNA encoding ß-actin, Spinophilin and Cortactin, whilst the expression of Profilin, α-actinin, Drebrin, Synaptopodin and Myosin decreased. By contrast, no changes were evident in Cofilin, Gelsolin and Arp2/3 mRNA. From this analysis, it appears that neither spinogenesis nor new mushroom spines are necessary for long-term spatial information retrieval, while thin spines could be potentiated to retrieve pre-learned spatial information. Further studies that focus on the signaling pathways and their related molecules may shed further light on the molecular dynamics of the plastic changes to dendritic spines that underlie cognitive performance, both under normal and pathological conditions.
Assuntos
Região CA1 Hipocampal/fisiologia , Proteínas do Citoesqueleto/fisiologia , Espinhas Dendríticas/fisiologia , Memória de Longo Prazo/fisiologia , Plasticidade Neuronal , Animais , Masculino , Ratos Sprague-Dawley , Aprendizagem Espacial/fisiologia , Memória Espacial/fisiologiaRESUMO
BACKGROUND: Methylphenidate (MPH) is a stimulant drug mainly prescribed to treat cognitive impairments in attention-deficit/hyperactivity disorder (ADHD). We demonstrated that neonatal hypoxia-ischemia (HI) induced attentional deficits in rats and MPH administration reversed these deficits. However, MPH effects on memory deficits after the HI procedure have not been evaluated yet. AIMS: We aimed to analyze learning and memory performance of young hypoxic-ischemic rats after MPH administration and associate their performance with brain-derived neurotrophic factor (BDNF) levels in the prefrontal cortex and hippocampus. METHODS: Male Wistar rats were divided into four groups (n=11-13/group): control saline (CTS), control MPH (CTMPH), HI saline (HIS) and HIMPH. The HI procedure was conducted at post-natal day (PND) 7 and memory tasks between PND 30 and 45. MPH administration (2.5 mg/kg, i.p.) occurred 30 min prior to each behavioral session and daily, for 15 days, for the BDNF assay (n=5-7/group). RESULTS: As expected, hypoxic-ischemic animals demonstrated learning and memory deficits in the novel-object recognition (NOR) and Morris water maze (MWM) tasks. However, MPH treatment did not improve learning and memory deficits of these animals in the MWM-and even disrupted the animals' performance in the NOR task. Increased BDNF levels were found in the hippocampus of HIMPH animals, which seem to have been insufficient to improve memory deficits observed in this group. CONCLUSIONS: The MPH treatment was not able to improve memory deficits resulting from the HI procedure considering a dose of 2.5 mg/kg. Further studies investigating different MPH doses would be necessary to determine a dose-response relationship in this model.
Assuntos
Estimulantes do Sistema Nervoso Central/farmacologia , Hipóxia-Isquemia Encefálica/tratamento farmacológico , Transtornos da Memória/tratamento farmacológico , Metilfenidato/farmacologia , Animais , Animais Recém-Nascidos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipóxia-Isquemia Encefálica/fisiopatologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/patologia , Ratos , Ratos WistarRESUMO
As pesquisas sobre o efeito do estresse crônico moderado (CMS) sobre a aprendizagem de não humanos apresentam resultados contraditórios. Este estudo investigou os efeitos do CMS sobre o desempenho de ratos em duas tarefas de aprendizagem: uma discriminação visual simultânea e uma aprendizagem espacial em labirinto aquático. Oito ratos Wistar machos foram divididos em grupo experimental (GE, exposto ao CMS) e grupo controle (GC). Após exposição do GE ao protocolo de CMS por três semanas, ambos os grupos passaram por uma tarefa de discriminação visual e pela tarefa de aprendizagem espacial no labirinto aquático de Morris (MWM), além de testes de preferência por solução de sacarose. O GE continuou sendo exposto ao CMS durante a tarefa de discriminação visual. Os resultados sugerem que o CMS pode ter reduzido o ganho de peso e dificultado a aprendizagem de discriminação visual do GE, sem alterações na preferência por sacarose e no MWM. De acordo com os resultados do presente estudo e da literatura em geral, os efeitos do CMS sobre a aprendizagem podem depender de sua duração e da complexidade da tarefa.
Researches on the effect of chronic mild stress (CMS) on non-human learning present contradictory results. This study investigated the effects of CMS on rats' performance in two learning tasks: a simultaneous visual discrimination and a spatial learning task in a water maze. Eight Wistar rats were divided into experimental group (GE, exposed to CMS) and control group (GC). After the GE group had been submitted to the CMS protocol for three weeks, both groups were exposed to a visual discrimination task and spatial learning task in the Morris Water Maze (MWM), in addition to preference tests for a sucrose solution. GE continued to be exposed to CMS for visual discrimination task. Results suggested that CMS may reduce weight gain and make the visual discrimination learning more difficult for the GE, without changes on the sucrose preference and MWM. According to the results of the present study and the literature in general, the effects of CMS on learning may depend on the duration and complexity of the task.
RESUMO
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.
Assuntos
Animais , Camundongos , Sistema Nervoso Central , Cognição , Aprendizagem Espacial , Mastigação , MemóriaRESUMO
The locus coeruleus (LC)-norepinephrine (NE) system modulates a range of salient brain functions, including memory and response to stress. The LC-NE system is regulated by neurochemically diverse inputs, including a range of neuropeptides such as arginine-vasopressin (AVP). Whilst the origins of many of these LC inputs, their synaptic connectivity with LC neurons, and their contribution to LC-mediated brain functions, have been well characterized, this is not the case for the AVP-LC system. Therefore, our aims were to define the types of synapses formed by AVP+ fibers with LC neurons using immunohistochemistry together with confocal and transmission electron microscopy (TEM), the origins of such inputs, using retrograde tracers, and the plasticity of the LC AVP system in response to stress and spatial learning, using the maternal separation (MS) and Morris water maze (MWM) paradigms, respectively, in rat. Confocal microscopy revealed that AVP+ fibers contacting tyrosine hydroxylase (TH)+ LC neurons were also immunopositive for vesicular glutamate transporter 2, a marker of presynaptic glutamatergic axons. TEM confirmed that AVP+ axons formed Gray type I (asymmetric) synapses with TH+ dendrites thus confirming excitatory synaptic connections between these systems. Retrograde tracing revealed that these LC AVP+ fibers originate from hypothalamic vasopressinergic magnocellular neurosecretory neurons (AVPMNNs). MS induced a significant increase in the density of LC AVP+ fibers. Finally, AVPMNN circuit upregulation by water-deprivation improved MWM performance while increased Fos expression was found in LC and efferent regions such as hippocampus and prefrontal cortex, suggesting that AVPMMN projections to LC could integrate homeostatic responses modifying neuroplasticity.
RESUMO
Objective: To determine whether performance in a virtual spatial navigational task is poorer in persistent postural perceptual dizziness (PPPD) patients than in healthy volunteers and patients suffering other vestibular disorders. Methods: Subjects were asked to perform three virtual Morris water maze spatial navigational tasks: (i) with a visible target, (ii) then with an invisible target and a fixed starting position, and finally (iii) with an invisible target and random initial position. Data were analyzed using the cumulative search error (CSE) index. Results: While all subjects performed equally well with a visible target, the patients with PPPD (n = 19) performed poorer (p < 0.004) in the invisible target/navigationally demanding tasks (CSE median of 8) than did the healthy controls (n = 18; CSE: 3) and vestibular controls (n = 19; CSE: 4). Navigational performance in the most challenging setting allowed us to discriminate PPPD patients from controls with an area under the receiver operating characteristic curve of 0.83 (sensitivity 78.1%; specificity 83.3%). PPPD patients manifested more chaotic and disorganized search strategies, with more dispersion in the navigational pool than those of the non-PPPD groups (standard distance deviation of 0.97 vs. 0.46 in vestibular controls and 0.20 in healthy controls; p < 0.001). Conclusions: While all patients suffering a vestibular disorder had poorer navigational abilities than healthy controls did, patients with PPPD showed the worst performance, to the point that this variable allowed the discrimination of PPPD from non-PPPD patients. This distinct impairment in spatial navigation abilities offers new insights into PPPD pathophysiology and may also represent a new biomarker for diagnosing this entity.
RESUMO
Unbalanced nutrition during perinatal period causes varying degrees of perturbations in the metabolism and cognitive functions of offspring. The aim of this study was to investigate effects of maternal and postweaning high-fat diet (HFD) exposure on the growth parameters, hippocampal functions and morphology of offspring in a sex-dependent manner. Spraque-Dawley rats were fed either standard (10 % fat) or saturated-fat (65 % fat) diet during their gestation and lactation period. After weaning, pups were sustained in same diet for 6 more weeks. Body mass index (BMI) of pups were monitored weekly, then spontaneous locomotor activities were recorded. Spatial learning and memory functions were analyzed by Morris Water Maze (MWM) test. Total volumetric changes of hippocampal subfields were estimated by Cavalieri method. HFD exposure produced sex-dependent alterations in BMI, serum lipid and activity levels. MWM results showed no significant difference among groups. However, retrieval indexes were higher in HFD-fed males. Total volumetric analysis of the dentate gyrus was comparable, but the pyramidal cell layer volume of HFD-fed males was lower than those of SD-fed males. Despite alterations in some growth and lipid parameters, maternal and perinatal exposure to HFD did not markedly affect cognitive functions and hippocampal morphology of offspring.
La nutrición desequilibrada durante el período perinatal causa diversos grados de perturbaciones en el metabolismo y las funciones cognitivas en neonatos. El objetivo de este estudio fue investigar los efectos de la exposición a una dieta alta en grasas (HFD) materna y posdestete en los parámetros de crecimiento, las funciones del hipocampo y la morfología de neonatos de una manera dependiente del sexo. Ratas SpragueDawley fueron alimentadas con dieta estándar (10 % grasa) o grasa saturada (65 % grasa) durante su período de gestación y lactancia. Después del destete, las crías se mantuvieron en la misma dieta durante 6 semanas. El índice de masa corporal (IMC) de las crías se controló semanalmente, luego se registraron las actividades locomotoras espontáneas. El aprendizaje espacial y las funciones de memoria se analizaron mediante la prueba Morris Water Maze (MWM). Los cambios volumétricos totales de los subcampos del hipocampo se estimaron mediante el método de Cavalieri. La exposición a HFD produjo alteraciones dependientes del sexo en el IMC, los niveles de lípidos séricos y los niveles de actividad. Los resultados de MWM no mostraron diferencias significativas entre los grupos. Sin embargo, los índices de recuperación fueron más altos en machos alimentados con HFD. El análisis volumétrico total del giro dentado fue comparable, pero el volumen de la capa de células piramidales de los machos alimentados con HFD fue menor que el de los machos alimentados con SD. A pesar de las alteraciones en algunos parámetros lipídicos y de crecimiento, la exposición materna y perinatal a HFD no afectó marcadamente las funciones cognitivas y la morfología del hipocampo de la descendencia.
Assuntos
Animais , Masculino , Feminino , Gravidez , Ratos , Efeitos Tardios da Exposição Pré-Natal , Gorduras na Dieta/efeitos adversos , Hipocampo/fisiopatologia , Hipocampo/patologia , Tamanho do Órgão , Ratos Sprague-Dawley , Aprendizagem em Labirinto , Fenômenos Fisiológicos da Nutrição Pré-Natal , Animais Recém-NascidosRESUMO
Abstract In this study we evaluated the long-term spatial memory in humans. A quasiexperimental design was used in which three groups of undergraduate students were trained in a virtual water maze to locate a hidden platform whose location was indicated by a set of cues. A pre-test without platform was performed prior to the training, and a post-test was conducted immediately after this (Group 0h), or after a retention interval of two (Group 48h) or seven days (Group 168h). For the pre-test, there was no evidence of preference for any area of the maze. Throughout the training trials, the time to find the goal decreased without differences between groups. During the post-test, all groups showed a preference for the reinforced quadrant, although the spent time, swimming distance, and accuracy of the search behavior in that area was equivalent between Group 0 h and Group 48 h, but higher than that shown by the Group 168 h. These data indicate changes in long-term spatial memory in humans, occurring after an interval of 48 h after its acquisition. The results are discussed on the basis of general memory processes and specific processes proposed by particular spatial memory theories. The clinical and comparative psychology implications are also addressed.
Resumo Neste estudo, avaliou-se a memória espacial de longo prazo em humanos. Para isso, empregou-se um desenho quase-experimental no qual se treinou três grupos de estudantes de graduação num labirinto virtual de água para localizar uma plataforma oculta cuja posição era sinalizada por um conjunto de chaves. Realizou-se um pré-teste sem plataforma antes do treinamento, e imediatamente depois se conduziu um pós-teste (Grupo 0 h), assim como depois de um intervalo de retenção de dois dias (Grupo 48 h) e de sete dias (Grupo 168 h). No pré-teste, não se encontrou evidência de preferência por alguma área do labirinto. Ao longo dos ensaios de treinamento, o tempo para encontrar a meta diminuiu sem diferenças entre grupos. Durante o pós-teste, todos os grupos mostraram uma preferência pelo quadrante reforçado, contudo o tempo de permanência, a distância de nado e a precisão do comportamento de busca nessa área foi equivalente entre o Grupo 0 h e o Grupo 48 h, embora maior à amostragem pelo Grupo 168 h. Esses dados indicam mudanças ocorridas 48 h depois da aquisição na memória espacial de longo prazo em humanos. Discutem-se os resultados a partir de processos gerais de memória e de processos específicos propostos por teorias particulares de memória espacial; ao final, abordam-se as implicações clínicas e pertinentes ao campo da psicologia comparada.
Resumen En este estudio se evaluó la memoria espacial a largo plazo en humanos. Para ello, se empleó un diseño cuasiexperimental en el que se entrenó a tres grupos de estudiantes de pregrado en un laberinto virtual de agua para localizar una plataforma oculta cuya ubicación era señalada por un conjunto de claves. Se realizó un pretest sin plataforma antes del entrenamiento, e inmediatamente después se condujo un postest (Grupo 0 h), así como después de un intervalo de retención de dos días (Grupo 48 h) y siete días (Grupo 168 h). En el pretest no se encontró evidencia de preferencia por alguna zona del laberinto. A lo largo de los ensayos de entrenamiento, el tiempo para encontrar la meta disminuyó sin diferencias entre grupos. Durante el postest, todos los grupos mostraron una preferencia por el cuadrante reforzado, sin embargo, el tiempo de permanencia, la distancia de nado y la precisión de la conducta de búsqueda en dicha zona fue equivalente entre el Grupo 0 h y el Grupo 48 h, aunque mayor a la mostrada por el Grupo 168 h. Estos datos indican cambios ocurridos 48 h después de la adquisición en la memoria espacial a largo plazo en humanos. Se discuten los resultados a partir de procesos generales de memoria y procesos específicos propuestos por teorías particulares de memoria espacial; y al final se abordan las implicaciones clínicas y pertinentes al campo de la psicología comparada.