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1.
Neuroimage ; 252: 119039, 2022 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-35227858

RESUMO

Ageing displays a low-grade pro-inflammatory profile in blood and the brain. Accumulation of pro-inflammatory cytokines, microglia activation and volumetric changes in the brain correlate with cognitive decline in ageing models. However, the interplay between them is not totally understood. Here, we aimed to globally identify an age-dependent pro-inflammatory profile and microglia morphological plasticity that favors major volume changes in the brain associated with cognitive decline. Cluster analysis of behavioral data obtained from 2-,12- and 20-month-old male C57BL/6 mice revealed age-dependent cognitive decline after the Y-maze, Barnes maze, object recognition (NORT) and object location tests (OLT). Global magnetic resonance imageing (MRI) analysis by deformation-based morphometry (DBM) in the brain identified a volume increase in the fornix and a decrease in the left medial entorhinal cortex (MEntC) during ageing. Notably, the fornix shows an increase in the accumulation of pro-inflammatory cytokines, whereas the left MEntC displays a decrease. Morphological assessment of microglia also confirms an active and dystrophic phenotype in the fornix and a surveillance phenotype in the left MEntC. Finally, biological modeling revealed that age-related volume increase in the fornix was associated with dystrophic microglia and cognitive impairment, as evidenced by failure on tasks examining memory of object location and novelty. Our results propose that the morphological plasticity of microglia might contribute to volumetric changes in brain regions associated with cognitive decline during physiological ageing.


Assuntos
Disfunção Cognitiva , Microglia , Envelhecimento , Animais , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/patologia , Citocinas , Humanos , Masculino , Transtornos da Memória/diagnóstico por imagem , Transtornos da Memória/patologia , Camundongos , Camundongos Endogâmicos C57BL , Memória Espacial/fisiologia
2.
J Neurosci ; 37(10): 2795-2801, 2017 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-28174334

RESUMO

Decades of research identify the hippocampal formation as central to memory storage and recall. Events are stored via distributed population codes, the parameters of which (e.g., sparsity and overlap) determine both storage capacity and fidelity. However, it remains unclear whether the parameters governing information storage are similar between species. Because episodic memories are rooted in the space in which they are experienced, the hippocampal response to navigation is often used as a proxy to study memory. Critically, recent studies in rodents that mimic the conditions typical of navigation studies in humans and nonhuman primates (i.e., virtual reality) show that reduced sensory input alters hippocampal representations of space. The goal of this study was to quantify this effect and determine whether there are commonalities in information storage across species. Using functional molecular imaging, we observe that navigation in virtual environments elicits activity in fewer CA1 neurons relative to real-world conditions. Conversely, comparable neuronal activity is observed in hippocampus region CA3 and the dentate gyrus under both conditions. Surprisingly, we also find evidence that the absolute number of neurons used to represent an experience is relatively stable between nonhuman primates and rodents. We propose that this convergence reflects an optimal ensemble size for episodic memories.SIGNIFICANCE STATEMENT One primary factor constraining memory capacity is the sparsity of the engram, the proportion of neurons that encode a single experience. Investigating sparsity in humans is hampered by the lack of single-cell resolution and differences in behavioral protocols. Sparsity can be quantified in freely moving rodents, but extrapolating these data to humans assumes that information storage is comparable across species and is robust to restraint-induced reduction in sensory input. Here, we test these assumptions and show that species differences in brain size build memory capacity without altering the structure of the data being stored. Furthermore, sparsity in most of the hippocampus is resilient to reduced sensory information. This information is vital to integrating animal data with human imaging navigation studies.


Assuntos
Evolução Biológica , Hipocampo/fisiologia , Memória Episódica , Rede Nervosa/fisiologia , Orientação/fisiologia , Animais , Medicina Baseada em Evidências , Macaca mulatta , Masculino , Especificidade da Espécie
3.
Neurobiol Learn Mem ; 140: 17-26, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28185871

RESUMO

Intense training refers to training mediated by emotionally arousing experiences, such as aversive conditioning motivated by relatively high intensities of foot-shock, which produces a strong memory that is highly resistant to extinction. Intense training protects memory consolidation against the amnestic effects of a wide variety of treatments, administered systemically or directly into brain structures. The mechanisms of this protective effect are unknown. To determine a potential neurobiological correlate of the protective effect of intense training, rats were trained in a one-trial step-through inhibitory avoidance task using different intensities of foot-shock (0.0, 0.5, 1.0, and 2.0mA). Some rats from each group were sacrificed 45min after training for immunohistochemical Arc protein detection in dorsal and ventral striatum; other rats were tested for extinction during six consecutive days, starting 48h after training. The results showed that training with 1.0 and 2.0mA produced optimal retention scores, which were significantly higher than those of the 0.5 and 0.0mA groups. Also, a higher resistance to extinction was obtained with 2.0mA than with the other intensities. A high number of neurons expressed Arc in ventral, but not in dorsal striatum in both the 1.0 and 2.0mA groups, with a larger area of Arc signal in the latter group. We conclude that an increased Arc expression may be related to enhanced synaptic plasticity in the ventral striatum, suggesting that it may be one of the physiological substrates of enhanced learning.


Assuntos
Aprendizagem da Esquiva/fisiologia , Condicionamento Operante/fisiologia , Corpo Estriado/metabolismo , Proteínas do Citoesqueleto/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Animais , Eletrochoque , Imuno-Histoquímica , Glicoproteínas de Membrana , Plasticidade Neuronal/fisiologia , Ratos , Ratos Wistar , Receptores de Interleucina-1 , Estriado Ventral/metabolismo
4.
J Neurosci ; 33(4): 1631-9, 2013 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-23345235

RESUMO

After spatial exploration in rats, Arc mRNA is expressed in ∼2% of dentate gyrus (DG) granule cells, and this proportion of Arc-positive neurons remains stable for ∼8 h. This long-term presence of Arc mRNA following behavior is not observed in hippocampal CA1 pyramidal cells. We report here that in rats ∼50% of granule cells with cytoplasmic Arc mRNA, induced some hours previously during exploration, also show Arc expression in the nucleus. This suggests that recent transcription can occur long after the exploration behavior that elicited it. To confirm that the delayed nuclear Arc expression was indeed recent transcription, Actinomycin D was administered immediately after exploration. This treatment resulted in inhibition of recent Arc expression both when evaluated shortly after exploratory behavior as well as after longer time intervals. Together, these data demonstrate a unique kinetic profile for Arc transcription in hippocampal granule neurons following behavior that is not observed in other cell types. Among a number of possibilities, this sustained transcription may provide a mechanism that ensures that the synaptic connection weights in the sparse population of granule cells recruited during a given behavioral event are able to be modified.


Assuntos
Proteínas do Citoesqueleto/biossíntese , Giro Denteado/metabolismo , Comportamento Exploratório/fisiologia , Regulação da Expressão Gênica/fisiologia , Proteínas do Tecido Nervoso/biossíntese , Neurônios/metabolismo , Animais , Genes Precoces , Hibridização in Situ Fluorescente , Masculino , Microscopia Confocal , RNA Mensageiro/análise , Ratos , Ratos Wistar , Comportamento Espacial/fisiologia , Transcrição Gênica , Transcriptoma
5.
Water Sci Technol ; 69(8): 1759-67, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24759539

RESUMO

The membrane fouling of an aerobic granular reactor coupled with a submerged membrane in a sequencing batch reactor (SBR) was evaluated. The fouling analysis was performed by applying microscopy techniques to determine the morphology and structure of the fouling layer on a polyvinylidene fluoride membrane. It was found that the main cause of fouling was the polysaccharide adsorption on the membrane surface, followed by the growth of microorganisms to form a biofilm.


Assuntos
Incrustação Biológica , Reatores Biológicos , Clorofenóis/química , Membranas Artificiais , Aerobiose , Clorofenóis/metabolismo , Poluentes da Água/química , Poluentes da Água/metabolismo
6.
Hippocampus ; 22(5): 1134-42, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-21695743

RESUMO

Adult-born neurons in the dentate gyrus (DG) can survive for long periods, are capable of integrating into neuronal networks, and are important for hippocampus-dependent learning. Neurogenesis is dramatically reduced during senescence, and it remains unknown whether those few neurons that are produced remain capable of network integration. The expression of Arc, a protein coupled to neuronal activity, was used to measure activity among granule cells that were labeled with BrdU 4 months earlier in young (9 months) and aged (25 months) Fischer344 rats. The results indicate that while fewer cells are generated in the senescent DG, those that survive are (a) more likely to respond to spatial processing by expressing Arc relative to the remainder of the granule cell population and (b) equally responsive to spatial exploration as granule cells of the same age from young animals. These findings provide compelling evidence that newborn granule cells in the aged DG retain the capacity for participation in functional hippocampal networks.


Assuntos
Envelhecimento/fisiologia , Proteínas do Citoesqueleto/metabolismo , Giro Denteado/metabolismo , Hipocampo/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Neurogênese/fisiologia , Neurônios/metabolismo , Análise de Variância , Animais , Bromodesoxiuridina/metabolismo , Giro Denteado/citologia , Hipocampo/citologia , Aprendizagem/fisiologia , Microscopia Confocal , Rede Nervosa/metabolismo , Plasticidade Neuronal/fisiologia , Ratos , Ratos Endogâmicos F344
7.
Learn Mem ; 18(10): 610-6, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21921210

RESUMO

The immediate early gene (IEG) Arc is known to play an important role in synaptic plasticity; its protein is locally translated in the dendrites where it has been involved in several types of plasticity mechanisms. Because of its tight coupling with neuronal activity, Arc has been widely used as a tool to tag behaviorally activated networks. However, studies examining the modulation of Arc expression during and after learning have yielded somewhat contradictory results. Although some have reported that higher levels of Arc were induced by initial acquisition of a task rather than by reinstating a learned behavior, others have failed to observe such habituation of Arc transcription. Moreover, most of these studies have focused on the mRNA and, surprisingly, relatively little is known about how learning can affect Arc protein expression levels. Here we used taste recognition memory and examined Arc protein expression in the insular cortex of rats at distinct times during taste memory formation. Interestingly, we found that more Arc protein was induced by a familiar rather than by a novel taste. Moreover, this increase was inhibited by post-trial intrahippocampal anisomycin injections, a treatment known to inhibit safe-taste memory consolidation. In addition, confocal microscopy analysis of immunofluorescence stained tissue revealed that the proportion of IC neurons expressing Arc was the same in animals exposed to novel and familiar taste, but Arc immunoreactivity in dendrites was dramatically higher in rats exposed to the familiar taste. These results provide novel insights on how experience affects cortical plasticity.


Assuntos
Córtex Cerebral/citologia , Proteínas do Citoesqueleto/metabolismo , Dendritos/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Neurônios/ultraestrutura , Reconhecimento Psicológico/fisiologia , Paladar/fisiologia , Vias Aferentes/fisiologia , Animais , Anisomicina/farmacologia , Condicionamento Operante/efeitos dos fármacos , Proteínas do Citoesqueleto/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/fisiologia , Masculino , Microscopia Confocal , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas do Tecido Nervoso/genética , Inibidores da Síntese de Proteínas/farmacologia , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Reconhecimento Psicológico/efeitos dos fármacos , Esquema de Reforço , Sacarina/administração & dosagem , Edulcorantes/administração & dosagem
8.
Foods ; 9(12)2020 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-33260727

RESUMO

A high consumption of soft drinks (SDs) has been linked with the development of anthropometric and metabolic alterations. We evaluate the association between SD consumption and some anthropometric and metabolic variables. This study is an observational study, using a sample of 394 university students, of which 158 were men (40.1%) and 238 women (59.9%), between 18 and 30 years. An SD intake questionnaire provided the consumption of different SDs. The participants' weight, height, and waist and hip circumferences were collected. Metabolic biomarkers were analyzed. The average intake of caloric SDs (CSDs) was 1193.6 ± 1534.8 mL/week and 84.5 ± 115.02 mL/week for non-caloric SDs (NCSDs). Sex differences were found in the amount of SD consumption and these statistical differences were driven by those men subjects with a high total body fat percentage (TBF%). In men, correlations were found between the intake of CSDs and the body mass index, waist and hip circumferences, TBF%, and visceral fat percentage. In woman, a correlation was found with glucose and triglycerides. The prediction model revealed that the intake of CSDs predicts TBF% and low-density lipoprotein only in men. A high amount of CSD consumption in men was associated with a high TBF%, and this may be predictive of future development of metabolic abnormalities.

9.
Behav Brain Res ; 379: 112373, 2020 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-31759047

RESUMO

The hippocampus plays a fundamental role in spatial learning and memory. Dentate gyrus (DG) granular neurons project mainly to proximal apical dendrites of neurons in the CA3 stratum lucidum and also, to some extent, to the basal dendrites of CA3 pyramidal cells in the stratum oriens. The terminal specializations of DG neurons are the mossy fibers (MF), and these huge axon terminals show expansion in the CA3 stratum oriens after the animals undergo overtraining in the Morris Water Maze task (MWM). However, to our knowledge there are no reports regarding the possible changes in density of post-synaptic targets of these terminals in the basal dendrites of CA3 neurons after overtraining in the MWM. The purpose of this work was to study the density of thorny excrescences (TE) and other dendritic spine types (stubby, thin, and mushroom) in the CA3 stratum oriens in animals overtrained in the MWM for three consecutive days and in animals trained for only one day. Seven days after MWM training, the animals were sacrificed, and their brains removed and processed for rapid Golgi staining to visualize the different types of dendritic protrusions. Our results revealed that the relative quantity of stubby, thin, and mushroom dendritic spines did not change, regardless of amount of training. However, a significant increase in the density of TE was detected in the overtrained animals. These results strongly suggest that spatial water maze overtraining induces an increased density of MF-TE connections, which might be functionally relevant for long-term spatial memory formation.


Assuntos
Região CA3 Hipocampal/citologia , Espinhas Dendríticas , Teste do Labirinto Aquático de Morris/fisiologia , Prática Psicológica , Células Piramidais , Animais , Região CA3 Hipocampal/fisiologia , Espinhas Dendríticas/fisiologia , Masculino , Memória de Longo Prazo/fisiologia , Células Piramidais/fisiologia , Ratos , Ratos Sprague-Dawley , Memória Espacial/fisiologia
10.
J Neurosci ; 26(47): 12237-41, 2006 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-17122048

RESUMO

Although it is established that new granule cells can be born and can survive in the adult mammalian hippocampus, there remains some question concerning the functional integration of these neurons into behaviorally relevant neural networks. By using high-resolution confocal microscopy, we have applied a new strategy to address the question of functional integration of newborn neurons into networks that mediate spatial information processing and memory formation. Exploration-induced expression of the immediate-early gene Arc in hippocampal cells has been linked to cellular activity observed in electrophysiological recordings under the same behavioral conditions. We investigated whether mature (5-month-old), newborn granule cells express Arc in response to a discrete spatial experience by detecting the expression of Arc in combination with NeuN (neuron-specific nuclear protein)-positive and bromodeoxyuridine-positive cells. We found that mature new granule cells do indeed express Arc in response to an exploration experience, supporting the idea that these cells are well integrated into hippocampal circuits. The proportion of mature newborn neurons that expressed Arc in response to exploration, however, was significantly higher (approximately 2.8%) than the proportion of cells that expressed Arc in the already existing population of granule cells (approximately 1.6%; p < 0.01). This finding extends previous data suggesting that the cellular physiology of newborn granule neurons differs from that of the existing population by indicating that these properties are retained in mature adult-generated neurons. Thus, these data have interesting implications for network models of spatial information processing and the role of hippocampal circuits in memory, indicating that mature new neurons are selectively recruited into hippocampal cell assemblies in higher proportions than older cells.


Assuntos
Comportamento Exploratório/fisiologia , Rede Nervosa/citologia , Rede Nervosa/fisiologia , Neurônios/fisiologia , Análise de Variância , Animais , Comportamento Animal , Bromodesoxiuridina/metabolismo , Contagem de Células/métodos , Proteínas do Citoesqueleto/metabolismo , Regulação da Expressão Gênica/fisiologia , Hipocampo/citologia , Imuno-Histoquímica/métodos , Técnicas In Vitro , Microscopia Confocal/métodos , Proteínas do Tecido Nervoso/metabolismo , Plasticidade Neuronal/fisiologia , Fosfopiruvato Hidratase/metabolismo , Ratos , Ratos Endogâmicos F344
11.
Neurochem Int ; 50(2): 404-17, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17101195

RESUMO

TRH administration induces arousal, improves cognition, and modulates glutamatergic and cholinergic transmission in hippocampal neurons. To study the possible involvement of TRH neurons in learning and memory processes, gene expression of TRH, its receptors, and pyroglutamyl peptidase (PPII), were measured in limbic regions of water-maze trained rats. Hypothalamus and amygdala showed changes related to the task but not specific to spatial learning while in hippocampus, pro-TRH and TRH-R1 mRNA levels were specifically increased in those animals trained to find a hidden platform. Variation of TRH content and mRNA levels of pro-TRH, TRH-R1, TRH-R2 and PPII are observed in conditions known to activate TRH hypophysiotropic neurons. Changes in some of these parameters could indicate the activation of TRHergic neurons and their possible involvement in some memory related process. Male Wistar rats were immersed (10 times) for 1, 3 or 5 days in a Morris water-maze containing, or not (yoked control) a platform and sacrificed 5, 30 and 60 min after last trial. TRH content and TSH serum levels were determined by radioimmunoassay; mRNA levels of pro-TRH, TRH-R1, TRH-R2, and PPII, by RT-PCR. Exclusive changes due to spatial training were observed in posterior hippocampus of rats trained for 5 days sacrificed after 60min: decreased TRH content and increased mRNA levels of pro-TRH and TRH-R1, particularly in CA3 region (measured by in situ hybridization). The hypothalamus-pituitary axis responded in both yoked and trained animals (increasing serum TSH levels and pro-TRH expression, due to swim-stress); in the amygdala of both groups, pro-TRH expression increased while diminished that of both receptors and PPII. Differential expression of these parameters suggests involvement of TRH hippocampal neurons in memory formation processes while changes in amygdala could relate to TRH anxiolytic role. The differential modulation in anterior and posterior portions of the hippocampus is discussed.


Assuntos
Sistema Límbico/metabolismo , Aprendizagem em Labirinto/fisiologia , Receptores da Tireotropina/biossíntese , Tireotropina/biossíntese , Animais , Autorradiografia , Hipocampo/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Hibridização In Situ , Sistema Límbico/enzimologia , Masculino , Memória/fisiologia , Piroglutamil-Peptidase I/metabolismo , RNA Mensageiro/biossíntese , Radioimunoensaio , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Glândula Tireoide/metabolismo
12.
J Neurosci ; 25(7): 1761-8, 2005 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-15716412

RESUMO

The immediate-early gene Arc is transcribed in neurons that are part of stable neural networks activated during spatial exploratory behaviors. Arc protein has been demonstrated to regulate AMPA-type glutamate receptor trafficking by recruiting endosomal pathways, suggesting a direct role in synaptic plasticity. The purpose of the present study is to examine the fidelity of Arc mRNA translation and the temporal dynamics of behaviorally induced Arc protein expression after rats explore a novel environment. These experiments reveal two waves of Arc protein expression after a single exploration session. In the initial wave, virtually all cells that express Arc mRNA in the hippocampus and parietal cortex also express Arc protein, indicating, at a cellular level, that mRNA transcription and translation are closely correlated from 30 min to 2 h in hippocampal CA and parietal neurons. A second wave of protein expression spans the interval from 8 to 24 h and is also remarkably specific to cells active in the original behavior-induced network. This second wave is detected in a subset of the original active network and displays the novel property that the proportions of Arc-positive neurons become correlated among regions at 24 h. This suggests that the second expression wave is driven by network activity, and the stabilization of circuits reflecting behavioral experience may occur in temporally discrete phases, as memories become consolidated. This is the first demonstration of network-selective translational events consequent to spatial behavior and suggests a role for immediate-early genes in circuit-specific, late-phase synaptic biology.


Assuntos
Proteínas do Citoesqueleto/biossíntese , Comportamento Exploratório/fisiologia , Genes Precoces , Hipocampo/fisiologia , Rede Nervosa/fisiologia , Proteínas do Tecido Nervoso/biossíntese , Lobo Parietal/fisiologia , RNA Mensageiro/biossíntese , Animais , Proteínas do Citoesqueleto/genética , Regulação da Expressão Gênica , Hipocampo/citologia , Processamento de Imagem Assistida por Computador , Masculino , Microscopia Confocal , Proteínas do Tecido Nervoso/genética , Plasticidade Neuronal/fisiologia , Neurônios/fisiologia , Lobo Parietal/citologia , RNA Mensageiro/genética , Ratos , Ratos Endogâmicos F344
13.
J Neurosci ; 25(3): 723-31, 2005 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-15659610

RESUMO

Neuroinflammation is associated with a variety of neurological and pathological diseases, such as Alzheimer's disease (AD), and is reliably detected by the presence of activated microglia. In early AD, the highest degree of activated microglia is observed in brain regions involved in learning and memory. To investigate whether neuroinflammation alters the pattern of rapid de novo gene expression associated with learning and memory, we studied the expression of the activity-induced immediate early gene Arc in the hippocampus of rats with experimental neuroinflammation. Rats were chronically infused with lipopolysaccharide (LPS) (0.25 mug/h) into the fourth ventricle for 28 d. On day 29, the rats explored twice a novel environment for 5 min, separated by 45 or 90 min. In the dentate gyrus and CA3 regions of LPS-infused rats, Arc and OX-6 (specific for major histocompatibility complex class II antigens) immunolabeling and Arc fluorescence in situ hybridization revealed both activated microglia (OX-6 immunoreactivity) and elevated exploration-induced Arc expression compared with control-infused rats. In contrast, in the CA1 of LPS-infused rats, where there was no OX-6 immunostaining, exploration-induced Arc mRNA and protein remained similar in both LPS- and control-infused rats. LPS-induced neuroinflammation did not affect basal levels of Arc expression. Behaviorally induced Arc expression was altered only within the regions showing activated microglia (OX-6 immunoreactivity), suggesting that neuroinflammation may alter the coupling of neural activity with macromolecular synthesis implicated in learning and plasticity. This activity-related alteration in Arc expression induced by neuroinflammation may contribute to the cognitive deficits found in diseases associated with inflammation, such as AD.


Assuntos
Proteínas do Citoesqueleto/genética , Encefalite/metabolismo , Comportamento Exploratório/fisiologia , Genes Precoces , Hipocampo/metabolismo , Microglia/metabolismo , Proteínas do Tecido Nervoso/genética , Animais , Proliferação de Células , Doença Crônica , Transtornos Cognitivos/metabolismo , Proteínas do Citoesqueleto/biossíntese , Encefalite/induzido quimicamente , Encefalite/patologia , Regulação da Expressão Gênica , Hipocampo/patologia , Lipopolissacarídeos , Masculino , Microglia/patologia , Proteínas do Tecido Nervoso/biossíntese , Biossíntese de Proteínas/fisiologia , Ratos , Ratos Endogâmicos F344 , Transcrição Gênica/fisiologia
14.
J Comp Neurol ; 498(3): 317-29, 2006 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-16871537

RESUMO

Active behavior, such as exploring a novel environment, induces the expression of the immediate-early gene Arc (activity-regulated cytoskeletal associated protein, or Arg 3.1) in many brain regions, including the hippocampus, neocortex, and striatum. Arc messenger ribonucleic acid and protein are localized in activated dendrites, and Arc protein is required for the maintenance of long-term potentiation and memory consolidation. Although previous evidence suggests that Arc is expressed in neurons, there is no direct demonstration that only neurons can express Arc. Furthermore, there is no characterization of the main neuronal types that express Arc. The data reported here show that behavior- or seizure-induced Arc expression in the hippocampus, primary somatosensory cortex, and dorsal striatum of rats colocalizes only with neuronal (NeuN-positive) and not with glial (GFAP-positive) cells. Furthermore, Arc was found exclusively in non-GABAergic alpha-CaMKII-positive hippocampal and neocortical neurons of rats that had explored a novel environment. Some GAD65/67-positive neurons in these regions were observed to express Arc, but only after a very strong stimulus (electroconvulsive seizure). In the dorsal striatum, spatial exploration induced Arc only in GABAergic and alpha-CaMKII-positive neurons. Combined, these results show that although a very strong stimulus (seizure) can induce Arc in a variety of neurons, behavior induces Arc in the CaMKII-positive principal neurons of the hippocampus, neocortex, and dorsal striatum. These results, coupled with recent in vitro findings of interactions between Arc and CaMKII, are consistent with the hypothesis that Arc and CaMKII act as plasticity partners to promote functional and/or structural synaptic modifications that accompany learning.


Assuntos
Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Proteínas do Citoesqueleto/metabolismo , Comportamento Exploratório/fisiologia , Proteínas do Tecido Nervoso/metabolismo , Plasticidade Neuronal/fisiologia , Neurônios/metabolismo , Prosencéfalo/metabolismo , Animais , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina , Corpo Estriado/citologia , Corpo Estriado/metabolismo , Proteínas do Citoesqueleto/genética , Proteínas de Ligação a DNA , Epilepsia/metabolismo , Epilepsia/fisiopatologia , Genes Precoces/fisiologia , Hipocampo/citologia , Hipocampo/metabolismo , Aprendizagem/fisiologia , Masculino , Proteínas do Tecido Nervoso/genética , Inibição Neural/fisiologia , Neurônios/citologia , Proteínas Nucleares/metabolismo , Prosencéfalo/citologia , Ratos , Ratos Endogâmicos F344 , Córtex Somatossensorial/citologia , Córtex Somatossensorial/metabolismo , Percepção Espacial/fisiologia , Transmissão Sináptica/fisiologia , Ácido gama-Aminobutírico/metabolismo
16.
PLoS One ; 10(8): e0132676, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26244549

RESUMO

Spatial water maze (WM) overtraining induces hippocampal mossy fiber (MF) expansion, and it has been suggested that spatial pattern separation depends on the MF pathway. We hypothesized that WM experience inducing MF expansion in rats would improve spatial pattern separation in the hippocampal network. We first tested this by using the the delayed non-matching to place task (DNMP), in animals that had been previously trained on the water maze (WM) and found that these animals, as well as animals treated as swim controls (SC), performed better than home cage control animals the DNMP task. The "catFISH" imaging method provided neurophysiological evidence that hippocampal pattern separation improved in animals treated as SC, and this improvement was even clearer in animals that experienced the WM training. Moreover, these behavioral treatments also enhance network reliability and improve partial pattern separation in CA1 and pattern completion in CA3. By measuring the area occupied by synaptophysin staining in both the stratum oriens and the stratun lucidum of the distal CA3, we found evidence of structural synaptic plasticity that likely includes MF expansion. Finally, the measures of hippocampal network coding obtained with catFISH correlate significantly with the increased density of synaptophysin staining, strongly suggesting that structural synaptic plasticity in the hippocampus induced by the WM and SC experience is related to the improvement of spatial information processing in the hippocampus.


Assuntos
Hipocampo/fisiologia , Fibras Musgosas Hipocampais/fisiologia , Plasticidade Neuronal/fisiologia , Comportamento Espacial/fisiologia , Memória Espacial/fisiologia , Sinapses/fisiologia , Animais , Comportamento Animal/fisiologia , Masculino , Aprendizagem em Labirinto/fisiologia , Ratos , Ratos Wistar , Transmissão Sináptica/fisiologia
17.
J Neuroinflammation ; 1(1): 12, 2004 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-15285803

RESUMO

BACKGROUND: Neuroinflammation plays a prominent role in the progression of Alzheimer's disease and may be responsible for degeneration in vulnerable regions such as the hippocampus. Neuroinflammation is associated with elevated levels of extracellular glutamate and potentially an enhanced stimulation of glutamate N-methyl-D-aspartate receptors. This suggests that neurons that express these glutamate receptors might be at increased risk of degeneration in the presence of chronic neuroinflammation. METHODS: We have characterized a novel model of chronic brain inflammation using a slow infusion of lipopolysaccharide into the 4th ventricle of rats. This model reproduces many of the behavioral, electrophysiological, neurochemical and neuropathological changes associated with Alzheimer's disease. RESULTS: The current study demonstrated that chronic neuroinflammation is associated with the loss of N-methyl-D-aspartate receptors, as determined both qualitatively by immunohistochemistry and quantitatively by in vitro binding studies using [3H]MK-801, within the hippocampus and entorhinal cortex. CONCLUSION: The gradual loss of function of this critical receptor within the temporal lobe region may contribute to some of the cognitive deficits observed in patients with Alzheimer's disease.

18.
J Neuroimmunol ; 131(1-2): 50-9, 2002 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-12458036

RESUMO

To investigate immune-to-brain communication, we challenged rats intraperitoneally with a protein antigen (keyhole limpet hemocyanin, KLH), and measured c-Fos expression in different brain structures. We found a rapid c-Fos expression 120 min after immunization in brain stem and forebrain structures, using a dose of KLH not inducing fever or malaise. Using proper controls, we found that this central response is related to the immunogenicity of the antigen and the magnitude of the immune response. Our results suggest that different interconnected brain cell groups respond rapidly to an immune challenge in the periphery, constituting an afferent pathway of neuroimmune communication.


Assuntos
Encéfalo/metabolismo , Hemocianinas/imunologia , Neuroimunomodulação , Proteínas Proto-Oncogênicas c-fos/biossíntese , Animais , Comportamento Animal/efeitos dos fármacos , Tronco Encefálico/química , Tronco Encefálico/metabolismo , Febre/imunologia , Expressão Gênica , Hemocianinas/administração & dosagem , Imunização , Imunoglobulinas/biossíntese , Imuno-Histoquímica , Cinética , Lipopolissacarídeos/farmacologia , Masculino , Prosencéfalo/química , Prosencéfalo/metabolismo , Proteínas Proto-Oncogênicas c-fos/análise , Proteínas Proto-Oncogênicas c-fos/imunologia , Ratos , Ratos Wistar
19.
Behav Brain Res ; 149(1): 49-59, 2004 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-14739009

RESUMO

It is well known that lead can affect several cognitive abilities in developing animals. In this work, we investigate the effects of different sub-chronic lead doses (0, 65, 125, 250 and 500 ppm of lead acetate in their drinking water for 14 days) in the performance of male adult rats in a water maze, cue maze and inhibitory avoidance tasks. We found that the acquisition of these tasks was not affected by lead, however, the highest dosage of lead (500 ppm) impaired memory consolidation in spatial and inhibitory avoidance tasks, but not in cue maze task while the 250 ppm dose only affected retrieval of spatial memory. Additionally, hippocampal long-term potentiation (LTP) induction in the perforant path after exposing adult rats to different doses of lead was studied. LTP induction was affected in a dose-dependent manner, and treatments of 250 and 500 ppm completely blocked LTP. We investigated the effects of lead intoxication on the activity of constitutive nitric oxide synthase (cNOS) in different brain regions of adult animals. The activity of cNOS was significantly inhibited in the hippocampus and cerebellum but not in the frontal cortex and brain stem, although lead had accumulated in all brain regions. These results suggest that lead intoxication can impair memory in adult animals and this impairment might be related with region-specific effects on cNOS activity.


Assuntos
Transtornos Cognitivos/fisiopatologia , Hipocampo/enzimologia , Intoxicação por Chumbo/fisiopatologia , Potenciação de Longa Duração/fisiologia , Memória/fisiologia , Óxido Nítrico Sintase/metabolismo , Análise de Variância , Animais , Aprendizagem da Esquiva , Tronco Encefálico/enzimologia , Cerebelo/enzimologia , Transtornos Cognitivos/etiologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Lobo Frontal/enzimologia , Chumbo/sangue , Intoxicação por Chumbo/complicações , Masculino , Aprendizagem em Labirinto , Via Perfurante/enzimologia , Ratos , Ratos Wistar , Sinaptossomos/fisiologia
20.
Rev. chil. nutr ; 46(3): 319-327, jun. 2019. tab
Artigo em Espanhol | LILACS | ID: biblio-1003710

RESUMO

RESUMEN En México, el consumo de bebidas endulzadas o refrescos es uno de los más altos a nivel mundial, esto representa un factor de riesgo para el desarrollo de obesidad y enfermedades metabólicas. En este estudio empleamos la Teoría de la Conducta Planeada (TCP) para identificar factores cognitivos asociados a la frecuencia de consumo de refrescos en adultos jóvenes mexicanos. Estudiamos una muestra de 261 personas, 110 hombres y 151 mujeres, de 18 a 45 años de edad (M= 22.51; DE = 4.2). Los participantes completaron cuestionarios de frecuencia de consumo e instrumentos basados en la TCP. Se encontraron dos factores predictores independientes y significativos de la frecuencia de consumo, el principal fue la baja autoeficacia, seguido por la intención. Ambos factores explican el 27.3% de la varianza de la frecuencia de consumo. Estos resultados contribuyen a entender los factores cognitivos involucrados en el consumo de refrescos, y sugieren que la alta frecuencia de consumo es una conducta no racional, por lo que podrían estar implicados aspectos afectivos y motivacionales, lo que deberá ser dilucidado con más investigación que permita explorar nuevas alternativas para el desarrollo de programas de prevención y tratamiento del consumo de bebidas con riesgo para la salud humana.


ABSTRACT Consumption of sugar sweetened beverages (SSB) in Mexico is one of the highest in the world, which represents a risk factor for the development of obesity and metabolic diseases. In the present study we used the Theory of Planned Behavior (TPB) to identify cognitive factors associated with the frequency of SSB consumption in Mexican young adults. We studied a sample of 261 people, 110 men and 151 women, from 18 to 45 years of age (M = 22.51, SD = 4.2). Participants completed consumption frequency questionnaires and instruments based on TPB. Two independent and significant predictors of consumption frequency were found: low self-efficacy and intention. Both factors explained 27.3% of the variance in consumption frequency. These results contribute to the understanding of the cognitive factors underlying SSB consumption, and suggest that high consumption frequency is a non-rational behaviour. It is possible that affective and motivational aspects could also be involved, which should be clarified with more research, in order to explore alternatives for the prevention and treatment of unhealthy consumption of beverages that are a risk to human health.


Assuntos
Adulto Jovem , Estudantes , Bebidas Gaseificadas , Ingestão de Líquidos , Comportamento Alimentar/psicologia , México
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