Privación sensorial temprana durante el neurodesarrollo y sus consecuencias cognitivas / Early sensory deprivation in neurodevelopment and its cognitive consequences / Privação sensorial precoce durante o neuro-desenvolvimento e suas consequências cognitivas

La aparición progresiva de habilidades sensoriales, motoras y cognitivo-afectivas en el humano a lo largo de su desarrollo es un reflejo de cambios fisiológicos que se gestan al interior del sistema nervioso. Dichos cambios hacen parte de procesos dinámicos y dependen, después del nacimiento, de la actividad eléctrica inducida por la experiencia. Considerando lo anterior, el sistema nervioso en desarrollo constituye una especie de protomapa, sobre el que la experiencia moldea características moleculares, neuroquímicas y de conectividad, que se reflejan en las actividades emergentes del sistema. La evidencia que soporta la importancia que la influencia experiencial tiene sobre el desarrollo del sistema nervioso viene en aumento. Esta revisión reúne información sobre estudios en modelos biológicos y en humanos sometidos a privación sensorial y ambiental. Se enfatiza en la caracterización de los rasgos cognitivos y sociales.

The progressive advent of sensory, motor, affective, and cognitive skills in the human being through its development, demonstrate physiological changes that are gestated within the nervous system. These processes are dynamic and dependent postnatally on electrical activity induced by experience. Taking this into account, the developing nervous system constitutes a protomap molded by experience dependent molecular, physiological and connectivity characteristics, which are reflected in the emergent principles of the system. The evidence that supports the importance of experience as influence over the development of this system has increased in the past years. This document gathers information about animal models and human studies enduring sensory and environmental deprivation, emphasizing in the characterization of their cognitive and social remarks.

O aparecimento progressivo de habilidades sensoriais, motoras e cognitivo-afetivas no humano ao longo do seu desenvolvimento é um reflexo de mudanças fisiológicas que se gestam no interior do sistema nervoso. Ditas mudanças fazem parte de processos dinâmicos e dependem, depois do nascimento, da atividade elétrica induzida pela experiência. Considerando o anterior, o sistema nervoso em desenvolvimento constitui uma espécie de "protomapa", sobre o que a experiência molda características moleculares, neuroquímicas e de conectividade, que se refletem nas atividades emergentes do sistema. A evidência que suporta a importância que a influência experiencial tem sobre o desenvolvimento do sistema nervoso vem em aumento. Esta revisão reúne informação sobre estudos em modelos biológicos e em humanos submetidos a privação sensorial e ambiental. Se enfatiza na caracterização das características cognitivas e sociais.

Comprendiendo el código neuronal: un análisis de cuatro perspectivas / Understanding the neural code: a four-perspective analysis

El objetivo de este artículo de revisión es dar a conocer diferentes perspectivas que han contribuido al estudio del Código Neuronal, un concepto que proviene de la Neurociencia y que explica el funcionamiento del cerebro a través de conexiones de neuronas. Se entregan cuatro ideas relacionadas con el análisis de este funcionamiento. En primer lugar, la propuesta de Convergencia Jerárquica, que ofrece una explicación asociada a un correlato neuronal específico para una conducta determinada. En segundo lugar, se aborda la idea del Código de Poblaciones, que explica el trabajo de un grupo de neuronas que representan un determinado estado. Posteriormente se expone la propuesta de Correlación Temporal, que plantea la presencia de poblaciones neuronales activas que se diferencian entre sí en base a patrones temporales de descarga para, finalmente, llegar al concepto de redes neuronales y sus diferentes modelos explicativos que han actuado como cimientos para el desarrollo de la Neurociencia moderna y que han sido desarrollados gracias a los aportes de la Biología, la Física, las Matemáticas, entre otras disciplinas, y que han generado las bases para la comprensión del funcionamiento del cerebro a través de neuronas interconectadas para lograr la expresión de los diferentes procesos cognitivos. El presente artículo pretende que el lector desarrolle una visión panorámica y general de cómo opera el flujo de la información que procesa el sistema nervioso central y el impacto que este fenómeno genera en el proceso de integración sensorial como parte de la emoción y la cognición en el cerebro humano.

The objective of this review article is to present different perspectives that have contributed to the study of the Neural Code, a concept that comes from Neuroscience and that explains the functioning of the brain through neuron connections. Four ideas related to the analysis of this functioning are presented. Firstly, the proposal of Hierarchical Convergence, which offers an explanation associated with a specific neuronal correlate for a specific behavior. Secondly, the idea of the Population Code is discussed, which explains the work of a group of neurons that represent a certain state. Subsequently, the proposal of Temporal Correlation is addressed, which proposes the presence of active neuronal populations that differentiate each other based on temporal discharge patterns, finally arriving at the concept of neural networks and their different explanatory models. The latter have acted as foundations for the development of modern Neuroscience and have been developed thanks to the contributions of Biology, Physics, Mathematics, among other disciplines, and have generated the basis for understanding the functioning of the brain through interconnected neurons to achieve the expression of the different cognitive processes. The paper aims to develop a panoramic and general view of how the flow of information processed by the central nervous system operates and the impact that this phenomenon generates in the process of sensory integration as part of emotion and cognition in the human brain.

Bases neurobiológicas del autismo y modelos celulares para su estudio experimental / Neurobiological bases of autism and cellular models for its experimental study

Los trastornos del espectro autista (TEA) son una alteración funcional de la corteza cerebral, que presenta anomalías estructurales del neurodesarrollo que afectan fundamentalmente a la función sináptica y el patrón de conexiones dentro y entre columnas corticales. Desde su aspecto etiológico, el TEA tiene una importante carga genética, considerándose un desorden derivado de una combinación de mutaciones "de novo", asociadas a una predisposición derivada de variaciones comunes heredadas. Las principales anomalías genéticas asociadas a TEA implican genes que codifican proteínas de la sinapsis. Así, en pacientes con TEA se han descrito alteraciones del desarrollo inicial de las sinapsis en los circuitos de conexión entre áreas corticales de procesamiento complejo. La complejidad molecular observada en la predisposición a desarrollar un TEA, junto con la diversidad de fenotipos estructurales neuronales, ha hecho que los modelos animales reproduzcan solo parcialmente el TEA. Para avanzar en el estudio experimental se hace pues necesario desarrollar modelos más representativos, como son los modelos celulares derivados de células humanas. En las últimas décadas, el desarrollo de la biología de las células madre nos da medios para acceder a paradigmas experimentales sobre células derivadas de individuos con TEA. Actualmente, los modelos de células plutipotentes inducidas (IPs) derivadas de células humanas permiten profundizar en el estudio de las bases moleculares y celulares del TEA. Sin embargo, presentan problemas inherentes derivados de la manipulación experimental que conlleva la reprogramación de la expresión génica, por lo que otros modelos celulares se están también postulando como válidos.

Autism Spectrum Disorders (ASD) are a functional alteration of the cerebral cortex, which presents structural neurodevelopmental anomalies that affect synaptic function and the pattern of connections within and between cortical columns. From its etiological aspect, ASD has an important genetic load, considering a polygenic disorder, derived from a combination of "de novo" genetic mutations, associated to a predisposition derived from common inherited variations. The main genetic anomalies associated with ASD involve genes that encode proteins of the synapse. Thus, in patients with ASD, alterations in the initial development of the synapses have been described in the connection circuits between complex processing cortical areas. The molecular complexity observed in the predisposition to develop an ASD, together with the diversity of structural phenotypes, has made animal models reproduce only partially the ASD. To advance in the experimental study it is therefore necessary to develop representative models, such as cellular models derived from human cells. In recent decades, the advances in stem cell biology give us a way to apply experimental paradigms in cells derived from individuals with ASD. Currently, induced pluripotent cells (IPs) derived from human adult cells allow deepening the study of molecular and cellular bases of the neuronal development in humans, as well as the anomalies in this development, which give rise to disorders such as ASD. However, they present inherent problems derived from the experimental manipulation that involves the reprogramming of gene expression, therefore other models are also been explored.

Cerebellar synaptopathy in streptozotocin-induced diabetic rats / Sinaptopatía cerebelosa en ratas diabéticas inducidas por estreptozotocina

SUMMARY: There is an increasing amount of evidence that supports the diabetic complications of the central nervous system structure and function. The cerebellum, which is one of the primary structure derived from the hindbrain, plays an important role in motor control, motor coordination, and non-motor functions, such as cognitive processing. The synapse is a critical structure that regulates neuronal communication, and well-defined afferent and efferent fibre connections in the cerebellum help in maintaining the proper working order. Thus, the present study sought to investigate the long-term effects of diabetes-induced synaptopathy in the cerebellum, using both histological and ultrastructural studies. Twenty Sprague-Dawley male rats were divided randomly into control and diabetic groups, and diabetes was then induced through a single intraperitoneal injection of streptozotocin (60 mg/kg body weight). Six month later, the rats were sacrificed and the cerebellum was removed. Light and electron microscopic examinations showed a degeneration of Purkinje cells (Neuron purkinjense) with shrunken cells, pyknotic nuclei, and synaptopathy, including the reduction in synapse density, number of synaptic vesicles, and maturation of synapses in the molecular layer of diabetic cerebellum. The disruptions in synaptic profiles, which observed in the diabetic condition, could be related to cerebellar dysfunction, thus leading to the defects in coordinated movement, balance, as well as cognitive learning and memory.

RESUMEN: Actualmente existe una creciente evidencia que apoya las complicaciones diabéticas de la estructura y función del sistema nervioso central. El cerebelo, una de las estructuras primarias del cerebro posterior, desempeña un papel importante en el control motor, la coordinación motora y las funciones no motoras, tanto como en el procesamiento cognitivo. La sinapsis es una estructura crítica que regula la comunicación neuronal y las conexiones de fibras aferentes y eferentes bien definidas en el cerebelo, ayudan a mantener el funcionamiento correcto. Por lo tanto, en el presente estudio se investigaron los efectos a largo plazo de la sinaptopatía inducida por la diabetes en el cerebelo, utilizando estudios histológicos y ultraestructurales. Veinte ratas SpragueDawley macho se dividieron al azar en grupos de control y diabetes, se indujó la diabetes a través de una inyección intraperitoneal única de estreptozotocina (60 mg / kg de peso corporal). Seis meses después, se sacrificaron las ratas y se extrajo el cerebelo. Los exámenes de microscopías óptica y electrónica mostraron una degeneración de las neuronas purkinjenses (células de Purkinje), con células reducidas, núcleos picnóticos y sinaptopatía, como también la densidad reducida de sinapsis, el número de vesículas sinápticas y la maduración de las sinapsis en la capa molecular del cerebelo de las ratas diabéticas. Las interrupciones en los perfiles sinápticos, que se observaron en la condición diabética, podrían estar relacionadas con la disfunción cerebelosa, lo que lleva a defectos en el movimiento coordinado, el equilibrio, así como al aprendizaje cognitivo y la memoria.

Educando en un ambiente enriquecido: porque todos estamos conectados / Educating in an enriched environment: because we are all connected

El objetivo de esta revisión es dar a conocer las diferentes vertientes que sustentan el proceso del aprendizaje en base a un concepto que ha alcanzado una gran importancia en los últimos años, el Ambiente Enriquecido (AE). Un término que ha sido emanado desde la biología, con diversos estudios de laboratorio realizados por científicos de renombre mundial y que, progresivamente ha ido incorporándose a disciplinas como la Psicología y la Pedagogía. En este artículo proponemos la descripción del impacto de este concepto en el proceso de aprendizaje experimentado por los seres humanos y su abordaje desde una perspectiva multidisciplinaria. Comenzamos por describir las bases neurofisiológicas del aprendizaje, con los fundamentos de la teoría neuronal como principal protagonista, pasando por la importancia de la Plasticidad Sináptica (PS) en el proceso de aprendizaje, el fenómeno de la Potenciación a Largo Plazo (PLP), como proceso generador de redes neuronales efectivas y sólidas. Posteriormente abordamos la génesis del Ambiente Enriquecido, con su origen en los experimentos con ratones de laboratorio, para posteriormente describir los conceptos y términos que han emanado del mismo que han sido aplicables a la Psicología Educacional tales como el Ambiente Desafiante, los instrumentos necesarios para su implementación y también el importante rol de las emociones en el proceso de aprendizaje de los sujetos. Finalmente, describimos el rol de la Pedagogía en la aplicación de actividades efectivas que conduzcan a un aprendizaje significativo en base al Ambiente Enriquecido.

The aim of this review is to present different strands that sustain the learning process based on a concept that has reached a major importance in recent years, the Enriched Environment (EE). A term that has been emerged from biology, with various laboratory studies conducted by world-renowned scientists and that has progressively been incorporated into disciplines such as Psychology and Education. In this article, we propose the description of the impact of this concept on the learning process experienced by human beings and its approach from a multidisciplinary perspective. We begin by describing the neurophysiological bases of learning, with the fundamentals of neuronal theory as the main protagonist, passing through the importance of Synaptic Plasticity (SP) in the learning process, the phenomenon of Long Term Potentiation (LTP), as a generating process of effective and solid neural networks. Subsequently, we covered the genesis of the Enriched Environment, with its origin in the experiments with laboratory mice, to later describe the concepts and terms that have emanated from it and have been applicable to Educational Psychology, such as Challenging Environment, the necessary instruments for its implementation and the important role of emotions in the subjects' learning process. Finally, we describe the role of Education in the implementation of effective activities that lead to meaningful learning based on the Enriched Environment.

Thiamine deficiency contributes to synapse and neural circuit defects

BACKGROUND: The previous studies have demonstrated the reduction of thiamine diphosphate is specific to Alzheimer's disease (AD) and causal factor of brain glucose hypometabolism, which is considered as a neurodegenerative index of AD and closely correlates with the degree of cognitive impairment. The reduction of thiamine diphosphate may contribute to the dysfunction of synapses and neural circuits, finally leading to cognitive decline. RESULTS: To demonstrate this hypothesis, we established abnormalities in the glucose metabolism utilizing thiamine deficiency in vitro and in vivo, and we found dramatically reduced dendrite spine density. We further detected lowered excitatory neurotransmission and impaired hippocampal long-term potentiation, which are induced by TPK RNAi in vitro. Importantly, via treatment with benfotiamine, Aß induced spines density decrease was considerably ameliorated. CONCLUSIONS: These results revealed that thiamine deficiency contributed to synaptic dysfunction which strongly related to AD pathogenesis. Our results provide new insights into pathogenesis of synaptic and neuronal dysfunction in AD.

História da neurotransmissão: um breve relato / History of neurotransmission: a brief report

Objetivos: Descrever, de forma resumida, as principais descobertas históricas referentes a aquisiçao dos conhecimentos acerca da neurotransmissão. Métodos: Foi realizada busca de artigos nas bases de dados LILACS, Pubmed, Medline, Up to date e Medscape, durante o período de janeiro a maio de 2018, com o critério de atualidade como publicado nos últimos cinco anos, bem como foi revisada literatura consagrada em Neurologia. Resultados: A história da neurotransmissão evoluiu gradualmente a partir do século XIX e ao longo dos anos através dos esforços meticulosos de um grande número personalidades históricas. Seu desenvolvimento foi de extrema relevância para a evolução médica nos campos da neurofisiologia, da neurologia, da neuropsiquiatria, da psicofarmacologia e da anestesia. Conclusões: Encontramos marcos fundamentais na evolução da história da neurotransmissão e das estruturas da arquitetura neuronal nela implicadas, desde a descoberta do neurônio, do impulso elétrico, dos neurotransmissores e de mecanismos de transdução celular, bem como os cientistas que realizaram essas descobertas, elementos importantes para a compreensão da neurobiologia do cérebro.

Objectives: To describe, in a summary form, the main historical findings regarding the acquisition of knowledge about neurotransmission. Methods: A search of articles in the LILACS, Pubmed, Medline, Up to date and Medscape databases was performed, with the current criterion as published in the last five years, as well as literature review consecrated in Neurology. Results: The history of neurotransmission evolved gradually from the nineteenth century and over the years through the meticulous efforts of a large number of historical personalities, Its development was extremely relevant to medical developments in the fields of neurophysiology, neurology, neuropsychiatry, psychopharmacology and anesthesia. Conclusions: We found key milestones in the evolution of the history of neurotransmission and the neuronal architecture structures involved, from the discovery of the neuron, the electrical impulse, neurotransmitters and cellular transduction mechanisms, as well as the scientists who made these discoveries, important elements to understand the neurobiology of the brain.

Neurotoxicidad alcohólica / Alcoholic neurotoxicity / Neurotoxicidade alcoólatra

El alcohol es un tóxico que, actúa como depresor del sistema nervioso central (SNC). Sus efectos son consecuencia directa de su acción sobre las membranas celulares y sobre los neurotransmisores. Las neuronas son particularmente sensibles al efecto neurotóxico del Etanol (EtOH) y su exposición afecta la morfología neuronal, ya que en estudios recientes se ha observado una disminución en la longitud del árbol dendrítico. El EtOH también produce cambios en la expresión de las proteínas sinápticas, aumento del lumen del retículo endoplasmático, así como también, desorganización del aparato de Golgi y de las mitocondrias. Objetivos: Describir los efectos del Etanol a nivel celular y molecular en el Sistema Nervioso Central y su repercusión en la salud humana. Métodos: Se realizó una búsqueda de literatura en las siguientes bases de datos disponibles en web: PubMed, ScienceDirect, Jama Journal, Scielo y portales de salud, utilizando las palabras claves: "etanol y farmacología", "alcohol y toxicología", "neurotoxicidad y etanol". Resultados: De las bases consultadas se obtuvo un total de 120 referencias de las cuales se aceptaron solo 55 que resaltan los aspectos más relevantes de la fisiopatología de la intoxicación con etanol y ciertos aspectos a nivel molecular relacionados con los efectos sobre el SNC. Conclusiones: Los efectos del EtOH sobre el sistema nervioso pueden ser consecuencia de un consumo agudo y excesivo o secundario a un consumo crónico, en relación a un estado de adicción y dependencia al mismo. La toxicidad sobre el sistema nervioso es consecuencia directa de la agresión del etanol o por diferentes trastornos metabólicos ligados a la toxicidad del mismo sobre otros órganos. La neurotoxicidad del alcohol se debe a la activación del sistema inmunitario innato en el cerebro, que promueve compuestos inflamatorios que serían los responsables del daño de la morfología neuronal, además de la alteración neuroanatómica de la corteza.

Alcohol is a toxic that acts as a central nervous system (CNS) depressant. Its effects are a direct consequence of its action on cell membranes and on neurotransmitters. Neurons are particularly sensitive to the neurotoxic effect of Ethanol (EtOH) and their exposure affects neuronal morphology, since a reduction in the length of the dendritic tree has recently been observed. EtOH also causes changes in the expression of synaptic proteins, increased endoplasmic reticulum light, as well as disorganization of the Golgi apparatus and mitochondria. Objectives: To describe the effects of Ethanol at the cellular and molecular level in the Central Nervous System and its repercussion on human health. Methods: A literature search was conducted in the following databases available on the web: PubMed, ScienceDirect, Jama Journal, Scielo and health portals, using the keywords: "ethanol and pharmacology", "alcohol and toxicology", "Neurotoxicity and ethanol". Results: From the databases consulted, a total of 120 references were obtained, of which 55 are accepted, highlighting the most relevant pathophysiology of ethanol intoxication and the minimum number of molecular levels related to the effects on the CNS. Conclusions: The effects of EtOH on the nervous system can be a consequence of an acute and excessive consumption or secondary to a chronic consumption, in relation to a state of addiction and dependence to it. The toxicity on the nervous system is the direct consequence of the aggression of ethanol and the different metabolic disorders linked to the toxicity of the same on other organs. The neurotoxicity of alcohol is due to the activation of the immune system in the brain, which promotes inflammatory cascade that cause those responsible for neuron damage, in addition to neuroanalytic alteration of the cortex.

O álcool é um tóxico que atua como um depressor do sistema nervoso central (SNC). Seus efeitos são conseqüência direta de sua ação nas membranas celulares e nos neurotransmissores. Os neurônios são particularmente sensíveis ao efeito neurotóxico do Etanol (EtOH) e sua exposição afeta a morfologia neuronal, uma vez que uma redução no comprimento da árvore dendrítica foi recentemente observada. EtOH também provoca alterações na expressão de proteínas sinápticas, aumento da luz do retículo endoplasmático, bem como desorganização do aparelho de Golgi e das mitocôndrias. Objetivos: Descrever os efeitos do Etanol no nível celular e molecular no Sistema Nervoso Central e sua repercussão na saúde humana. Métodos: Uma investiga çao bibliográfica foi realizada nos seguintes bancos de dados disponíveis na web: PubMed, ScienceDirect, Jama Journal, Scielo E portais de saúde, usando as palavras-chave: "ethanol and pharmacology", "Álcool e toxicologia", "Neurotoxicidade e etanol". Resultados: partir dos bancos de dados consultados, foram obtidas 120 referências, das quais 55 são aceitas, destacando a fisiopatologia mais relevante da intoxicação por etanol e o número mínimo de níveis moleculares relacionados aos efeitos no SNC. Conclusões: Os efeitos do EtOH no sistema nervoso podem ser uma conseqüência de um consumo agudo e excessivo ou secundário a um consumo crônico, em relação a um estado de dependência e dependência. A toxicidade no sistema nervoso é a conseqüência direta da agressão do etanol e dos diferentes distúrbios metabólicos ligados à toxicidade do mesmo em outros órgãos. A neurotoxicidade do álcool deve-se à ativação do sistema imunológico no cérebro, que promove a cascata inflamatória que causa os responsáveis pelo dano neuronal, além da alteração neuroanalítica do córtex.

Neurotoxicidad de los plaguicidas como agentes disruptores endocrinos: una revisión / Neurotoxicity of pesticides as endocrine disruptors agents: a review

Los plaguicidas se encuentran en el medio ambiente como contaminantes formando mezclas complejas, los estudios recientes se han centrados en la evaluación de los efectos y riesgos que pueden causar estas mezclas de plaguicidas en el ser humano y los ecosistemas.Esta revisión hace hincapié a tres plaguicidas específicos, representativos de los grupos químicos organofosforados, carbamato de tipo ditiocarbamato y triazinas, como son: Paratión® etílico, Mancozeb® y Atrazina®, respectivamente. Ha sido demostrado en animales de experimentación la neurotoxicidad de estos plaguicidas por alteración de la transmisión sináptica y de los mecanismos de la homeostasis del sistema neuroendocrino, lo cual explica la acción de estos plaguicidas como disruptores endocrinos. Varios trabajos demuestran que estos plaguicidas son potencialmente tóxicos a la salud humana, y aún en bajas concentraciones, pueden afectar al organismo causando alteraciones en el sistema neuroendocrino, especialmente en los ejes hipotálamo-hipófisis-gónada e hipotálamo-hipófisis-tiroides. Los investigadores destacan que los momentos de particular sensibilidad de la exposición a plaguicidas disruptores endocrinos son las etapas tempranas de la vida como: durante el desarrollo embrionario y la primera infancia, períodos en los cuales los procesos de crecimiento son controlados por las hormonas afectando el desarrollo del cerebro, el sistema inmune y otros órganos como el sistema reproductor y tiroideo. Los cambios neuroquímicos provocados por la exposición a estos plaguicidas durante el desarrollo cerebral constituyen un alto riesgo porque son capaces de interferir en los procesos de neurogénesis y sinaptogénesis, afectando de manera adversa las funciones cognitivas y motoras, cuyos efectos se observan durante las etapas posteriores de la vida.

Pesticides are found in the environment as complex mixtures forming pollutants, recent studies have focused on evaluating the effects and risks that may cause these mixtures of pesticides on humans and ecosystems. This review highlights three specific, representative of organophosphorus pesticide chemical groups carbamate, dithiocarbamate and triazine type, such as: ethyl Paratión®, Mancozeb® and Atrazina®, respectively.It has been demonstrated in experimental animal’s neurotoxicity of these pesticides by altering synaptic transmission and mechanisms of homeostasis of the neuroendocrine system, which explains the action of these pesticides as endocrine disruptors. Several studies show that these pesticides are potentially toxic to human health, and even in low concentrations, can affect the body causing alterations in the neuroendocrine system, especially in the hypothalamic-pituitary-gonadal and hypothalamic-pituitary-thyroid axis. The researchers point out that the moments of particular sensitivity of exposure Endocrine disruptor pesticide are the early stages of life as during embryonic development and early childhood periods in which growth processes are controlled by hormones affecting the development brain, immune system and other organs such as the thyroid and reproductive system. The neurochemical changes induced by exposure to these pesticides during brain development are at high risk because they are able to interfere with the processes of neurogenesis and synaptogenesis, adversely affecting cognitive and motor functions, whose effects are observed during the later stages of life.

Quantitative Assessment of Root Canal Roughness with Calcium-Based Hypochlorite Irrigants by 3D CLSM

Chemical solutions play important roles in endodontic treatment and promote ultrastructural changes in dentin surface. The aim of this study was to quantify root canal roughness at different concentrations of calcium hypochlorite (Ca(OCl)2) and sodium hypochlorite (NaOCl) by confocal laser scanning microscopy (CLSM). Fifty-two human mandibular premolars were sectioned and randomly organized into thirteen groups (n=8): saline (control); 1%, 2.5% and 5% NaOCl; 1%, 2.5% and 5% Ca(OCl)2; the hypochlorite groups were further divided into with or without EDTA. The chlorine concentrations of the different solutions were measured by iodine titration (%). The superficial roughness (Sa) was quantified by CLSM. Ca(OCl)2 presented substantial decrease in chlorine concentration that differed from the package indication, but without compromising the dentin ultrastructure changes. There were no significant differences in dentin roughness between Ca(OCl)2 or NaOCl at all studied concentrations. The combination with EDTA provided similar roughness values among the solutions (p>0.05). The 5% Ca(OCl)2 and NaOCl solutions significantly increased dentin roughness and did not differ from the EDTA association (p>0.05). Ca(OCl)2 promoted similar dentin roughness as the NaOCl at the same concentrations and combined with EDTA. It may be concluded that Ca(OCl)2 modified the root canal dentin roughness similarly to NaOCl, at the same concentrations and EDTA combinations used in this study. Ca(OCl)2 and NaOCl, both at 5%, significantly altered dentin roughness, overcoming EDTA association, thus Ca(OCl)2 concentrations ranging from 1% to 2.5% may be suitable solutions for root canal irrigation protocols.

Soluções químicas são fundamentais para o tratamento endodôntico; entretanto, promovem alterações ultraestruturais na superfície dentinária. O objetivo deste estudo foi quantificar a rugosidade da dentina radicular com diferentes concentrações de hipoclorito de cálcio (Ca(OCl)2) e hipoclorito de sódio (NaOCl) utilizando microscopia confocal à laser (CLSM). Foram utilizados 52 premolares humanos inferiores e aleatoriamente divididos em treze grupos (n=8): Soro fisiológico (controle); NaOCl a 1%, 2,5% and 5%; Ca(OCl)2 a 1%, 2,5% and 5%; os grupos de hipoclorito foram subdivididos pela associação ou não ao ácido etilenodiaminotetracético (EDTA). A concentração de cloro ativo foi avaliada para diferentes soluções utilizando titulação iodométrica (%). A rugosidade superficial (Sa) foi quantificada por CLSM. Ca(OCl)2 apresentou perda substancial de cloro ativo e que foi distinta da condição descrita pelo fabricante, sem entretanto comprometer as alterações no substrato dentinário. Não houve diferenças significantes na rugosidade dentinária produzida pelos Ca(OCl)2 e NaOCl em todas as concentrações estudadas e associação com EDTA. A associação ao EDTA produziu rugosidade semelhante entre as soluções (p>0.05). O Ca(OCl)2 e NaOCl na concentração de 5% aumentaram significativamente a rugosidade dentinária e não apresentaram diferenças dos valores obtidos com a associação de EDTA (p>0.05). O Ca(OCl)2 alterou a rugosidade da dentina radicular de forma semelhante ao NaOCl, nas concentrações e associações utilizadas neste estudo. Como a concentração de 5% de Ca(OCl)2 e NaOCl, apresentou maior rugosidade dentinária, independente da associação ao EDTA, pode-se concluir que Ca(OCl)2 nas concentrações de 1% e 2,5% pode ser considerado uma solução adequada para a irrigação de canais radiculares.

Effect of a Surfactant on the Antimicrobial Activity of Sodium Hypochlorite Solutions

The objective of the present study was to evaluate the antimicrobial activity of sodium hypochlorite (NaOCl) associated with a surfactant. Seventy single-rooted extracted human teeth were inoculated with Enterococcus faecalis, and incubated for 21 days (37 °C). The groups were distributed according to the irrigation solution used during root canal preparation: 5%, 2.5% and 1% NaOCl; 5%, 2.5% and 1% Hypoclean(r), a solution containing a surfactant (cetrimide) associated with NaOCl. Three microbiological samples were collected from each tooth: S1 - before instrumentation; S2 - immediately after instrumentation; and S3 - after a seven-day period. Data were submitted to ANOVA and Tukey test with 5% significance level. The results showed that immediately after root canal preparation (S2), E. faecalis was eliminated in all the experimental groups. However, after 7 days (S3), only the groups in which Hypoclean was used, remained contamination-free, including Hypoclean associated with 1% NaOCl, while the root canals irrigated with 1% NaOCl only, presented the highest percentage of bacterial growth. In conclusion, the addition of surfactant increased the antimicrobial activity of 1% NaOCl to levels similar to 5% NaOCl.

O objetivo da presente pesquisa foi avaliar a atividade antimicrobiana de hipoclorito de sódio (NaOCl), associado a um tensoativo. Setenta dentes humanos monorradiculares extraídos foram inoculados com Enterococcus faecalis e incubados durante 21 dias (37 °C). Os grupos foram distribuídos de acordo com a solução irrigadora utilizada no preparo do canal: hipoclorito de sódio a 5%, 2,5% e 1%; Hypoclean(r) a 5%, 2,5% e 1% - uma solução contendo um surfactante (cetrimida) associado com NaOCl. Três amostras microbiológicas foram coletadas de cada dente: S1 - antes de instrumentação; S2 - imediatamente após a instrumentação; e S3 - após um período de sete dias. Os dados foram submetidos à análise de variância e teste de Tukey com 5% de nível de significância. Os resultados mostraram que imediatamente após o preparo do canal radicular (S2), o E. faecalis foi eliminado em todos os grupos experimentais. No entanto, após 7 dias (S3), apenas os grupos em que se utilizou Hypoclean permaneceram livres de contaminação, incluindo Hypoclean 1%, enquanto que os canais radiculares irrigados apenas com hipoclorito de sódio 1% apresentaram a mais elevada percentagem de crescimento bacteriano. Em conclusão, a adição de surfactante aumentou a atividade antimicrobiana de 1% de NaOCl a níveis semelhantes aos do NaOCl 5% .

Un primer análisis de la investigación en México sobre los determinantes sociales de la salud: 2005-2012 / A first analysis of research on social determinants of health in Mexico: 2005-2012

Objetivo. Examinar la investigación hecha en México sobre los determinantes sociales de la salud (DSS) durante el periodo 2005-2012 con base en la caracterización del sistema nacional de investigación en salud y la producción científica sobre este tema. Material y métodos. Análisis en dos etapas: revisión documental de fuentes oficiales sobre investigación en salud en México y búsqueda sistemática de literatura sobre DSS. Resultados. Los DSS fueron mencionados en el Programa de Acción Específico de Investigación en Salud 2007-2012, pero no figuran en las estrategias y objetivos; en su lugar, se enfatizan primordialmente aspectos de infraestructura y administrativos. En el periodo se publicaron 145 artículos sobre DSS, cuyas temáticas más abordadas fueron "condiciones de salud", "sistemas de salud" y "nutrición y obesidad". Conclusiones. A pesar de que existe investigación en México sobre DSS, la instrumentación de esos hallazgos en políticas de salud no se ha implementado. El Programa Sectorial de Salud 2013-2018 representa una ventana de oportunidad para posicionar resultados de investigación que promuevan políticas de equidad en salud.

Objective. To examine the research on social determinants of health (SDH) produced in Mexico during the period 2005-2012, based on the characterization of the national health research system and the scientific production on this topic. Materials and methods. Two-stage analyses: Review of Mexican documents and official sources on health research and systematic bibliographic review of the literature on SDH. Results. Although SDH were mentioned in the Specific Action Plan for Health Research 2007-2012, they are not implemented in strategies and goals, as the emphasis is put mostly in infrastructure and administrative aspects of research. In the period studied, 145 articles were published on SDH topics such as health conditions, health systems and nutrition and obesity. Conclusions. In spite of the availability of research on SDH in Mexico, the operationalization of such findings into health policies has not been possible. The current Sectorial Program on Health 2013-2018 represents a window of opportunity to position research findings that promote health equity policies.

Renovación sináptica y evolución: el eje de la plasticidad cerebral / Synaptic renewal and evolution: the axis of brain plasticity

El famoso Psicólogo estadounidense William James, fue el primero en hablar de plasticidad hacia el año de 1890, para describir la modificación de las redes neuronales. Autores como Santiago Ramon y Cajal, Arenander, de Vellis, Clark C. Speidel, entre otros aportaron igualmente al estudio de la sinaptogénesis, su evolución y su renovación; gracias a ellos se ha podido dar cabida y ampliación, a este fenómeno de supervivencia del cerebro. El estudio de la neuroplasticidad constituye uno de los aportes más importantes, que se está dando a la educación en los últimos tiempos. Se trata de una capacidad del cerebro, que le permite aumentar o disminuir el número de ramificaciones neuronales y de sinapsis, a partir del estímulo sobre el córtex cerebral (Acharya, Shukla, Mahajan & Diwan, 2012). Así es como se comprende que la neuroplasticidad sea la base estructural del aprendizaje, porque existe una estrecha relación entre estímulos internos y externos recibidos, y el proceso de transformación del cerebro a lo largo de toda la vida

The famous American psychologist William James, was the first to speak of plasticity around the year 1890, to describe the modification of neural networks. Authors such as Santiago Ramon y Cajal, Arenander, de Vellis, Clark C. Speidel, among others also contributed to the study of synaptogenesis, its evolution and its renewal; thanks to them it has been possible to accommodate and expand this phenomenon of brain survival. The study of neuroplasticity constitutes one of the most important contributions, which is being given to education in recent times. It is a capacity of the brain, which allows it to increase or decrease the number of neuronal branches and synapses, based on the stimulus on the cerebral cortex (Acharya, Shukla, Mahajan & Diwan, 2012). This is how it is understood that neuroplasticity is the structural basis of learning, because there is a close relationship between internal and external stimuli received, and the process of transformation of the brain throughout life

Evidence of presynaptic and postsynaptic action of local anesthetics in rats

PURPOSE: To assess the probable actions of ropivacaine, 50% enantiomeric excess bupivacaine mixture (S75-R25) and levobupivacaine on neuromuscular transmission in vitro. METHODS: Thirty rats were distributed into groups (n=5) according to the drug used: ropivacaine, bupivacaine (S75-R25) and levobupivacaine. The concentration used for the three local anesthetics (LA) was 5 µg.mL.-1The following parameters were evaluated: 1) LA effects on membrane potential (MP) and miniature end plate potential (MEPP). A chick biventer cervicis preparation was also used to evaluate LA effects on the contracture response to acetylcholine. RESULTS: LA did not alter MP values and decreased the frequency and amplitude of MEPP. In a chick biventer cervicis preparation, bupivacaine (S75-R25) and levobupivacaine decreased the contracture response to acetylcholine with statistical significance, in comparison to ropivacaine. CONCLUSIONS: In the concentrations used, levobupivacaine and bupivacaine (S75-R25) exhibited presynaptic and postsynaptic actions evidenced by alterations in miniature end plate potentials and contracture response to acetylcholine. Ropivacaine only had a presynaptic action.

Glia: dos velhos conceitos às novas funções de hoje e as que ainda virão / Glia: from old concepts to new functions today and yet to come

Descritas há mais de 150 anos, as células gliais, constituintes do tecido nervoso juntamente com os neurônios, foram consideradas até pouco tempo células de suporte do cérebro, passivas e à margem do seu funcionamento. Especialmente na última década, as neurociências foram palco de uma mudança de paradigma relacionada à função e ao papel dessas células na fisiologia e patologia neurais. Neste artigo, discutimos como os avanços acerca do conhecimento sobre os astrócitos, o mais abundante tipo glial, contribuíram para o entendimento do funcionamento cerebral. Apresentamos evidências da relação entre disfunções gliais e doenças neurodegenerativas e desordens neurológicas, discutindo o potencial papel dessas células na elaboração de abordagens terapêuticas para o sistema nervoso adulto.

New frontiers in the study of memory mechanisms

We review recent work on three major lines of memory research: a) the possible role of the protein kinase M-zeta (PKMzeta) in memory persistence; b) the processes of “synaptic tagging and capture” in memory formation; c) the modulation of extinction learning, widely used in the psychotherapy of fear memories under the name of “exposure therapy”. PKMzeta is a form of protein kinase C (PKC) that apparently remains stimulated for months after the consolidation of a given memory. Synaptic tagging is a mechanism whereby the weak activation of one synapse can tag it with a protein so other synapses in the same cell can reactivate it by producing other proteins that bind to the tag. Extinction, once mistakenly labeled as a form of forgetting, is by itself a form of learning; through it animals can learn to inhibit a response. We now know it can be modulated by neurotransmitters or by synaptic tagging, which should enable better control of its clinical use.

Relationships between dendritic morphology, spatial distribution and firing patterns in rat layer 1 neurons

The cortical layer 1 contains mainly small interneurons, which have traditionally been classified according to their axonal morphology. The dendritic morphology of these cells, however, has received little attention and remains ill defined. Very little is known about how the dendritic morphology and spatial distribution of these cells may relate to functional neuronal properties. We used biocytin labeling and whole cell patch clamp recordings, associated with digital reconstruction and quantitative morphological analysis, to assess correlations between dendritic morphology, spatial distribution and membrane properties of rat layer 1 neurons. A total of 106 cells were recorded, labeled and subjected to morphological analysis. Based on the quantitative patterns of their dendritic arbor, cells were divided into four major morphotypes: horizontal, radial, ascendant, and descendant cells. Descendant cells exhibited a highly distinct spatial distribution in relation to other morphotypes, suggesting that they may have a distinct function in these cortical circuits. A significant difference was also found in the distribution of firing patterns between each morphotype and between the neuronal populations of each sublayer. Passive membrane properties were, however, statistically homogeneous among all subgroups. We speculate that the differences observed in active membrane properties might be related to differences in the synaptic input of specific types of afferent fibers and to differences in the computational roles of each morphotype in layer 1 circuits. Our findings provide new insights into dendritic morphology and neuronal spatial distribution in layer 1 circuits, indicating that variations in these properties may be correlated with distinct physiological functions.

Aspectos da fisiopatologia da doença de Alzheimer esporádica / Pathophysiological features of sporadic Alzheimer's disease

A doença de Alzheimer (DA) é a forma de demência degenerativa esporádica mais comum. Caracteristicamente ocorre expressiva perda neuronal progressiva em locais específicos nas pessoas atingidas. O distúrbio degenerativo progressivo se caracteriza pela perda de sinapses, de neurônios cerebrais e por depósitos de fibrilas de peptídeos de beta-amilóide extraneuronais, constituindo as placas senis e a presença de agregados intraneuronais da proteína tau, formando os emaranhados neurofibrilares. Fatores genéticos, metabólicos, neuroinflamação, alterações mitocondriais, distúrbios vasculares e processos oxidativos estão envolvidos no desencadear e manutenção de várias doenças neurodegenerativas, incluindo a DA. Todas essas alterações participam no processo fisiopatológico da doença. O objetivo desta revisão é mostrar a associação das várias causas subjacentes ao processo fisiopatológico da DA, com vistas ao desenvolvimento de marcadores biológicos e estratégias terapêuticas.

Alzheimer's disease (AD) is the most common form of sporadic degenerative dementia. Characteristically there is an expressive neuronal loss in specific sites in the affected persons. The progressive degenerative disorder is characterized by synaptic loss, of brain neurons, and by extraneuronal deposition of beta-amyloid fibrils, constituting the senile plaques, and the presence of intraneuronal aggregates of tau protein, forming the neurofibrillary tangles. Genetic factors, metabolic, neuroinflammation, mitochondrial disturbances, vascular disorders and oxidative processes are involved in the onset and maintenance of several neurodegenerative disorders, including AD. All these disturbances participate in the pathophysiological process of the disease. The aim of this review is to show the association of the varied causes underlying the pathophysiological process of AD, having in view the development of biological markers and therapeutic strategies.

Synaptic vesicle cycling is not impaired in a glutamatergic and a cholinergic synapse that exhibit deficits in acidification and filling

The purpose of the present work was to investigate synaptic vesicle trafficking when vesicles exhibit alterations in filling and acidification in two different synapses: a cholinergic frog neuromuscular junction and a glutamatergic ribbon-type nerve terminal in the retina. These synapses display remarkable structural and functional differences, and the mechanisms regulating synaptic vesicle cycling might also differ between them. The lipophilic styryl dye FM1-43 was used to monitor vesicle trafficking. Both preparations were exposed to pharmacological agents that collapse ΔpH (NH4Cl and methylamine) or the whole ΔµH+ (bafilomycin), a necessary situation to provide the driving force for neurotransmitter accumulation into synaptic vesicles. The results showed that FM1-43 loading and unloading in neuromuscular junctions did not differ statistically between control and experimental conditions (P > 0.05). Also, FM1-43 labeling in bipolar cell terminals proved highly similar under all conditions tested. Despite remarkable differences in both experimental models, the present findings show that acidification and filling are not required for normal vesicle trafficking in either synapse.

O objetivo do presente trabalho foi investigar o tráfego de vesículas sinápticas quando estas apresentam alterações no armazenamento de neurotransmissores e acidificação em duas distintas sinapses: a junção neuromuscular colinérgica de rãs versus o terminal nervoso glutamatérgico do tipo ribbon em céulas bipolares da retina. Essas sinapses exibem notáveis diferenças estruturais e funcionais e os mecanismos de regulação de ciclo das vesículas sinápticas podem ser diferentes entre eles. Para monitorar o tráfego de vesícula, foi utilizado o marcador lipofílico FM1-43. Ambas as preparações foram expostas a agentes farmacológicos que provocam o colapso de ΔpH (NH4Cl e metilamina) ou de todo ΔµH+ (bafilomicina), gradientes necessários para o acúmulo de neurotransmissores em vesículas sinápticas. Nossos resultados demonstram que a marcação e desmarcação de FM1-43 nas junções neuromusculares não foi estatisticamente diferente entre as diversas condições experimentais (P > 0,05). Além disso, a marcação de FM1-43 em terminais sinápticos de células bipolares foram bastante semelhantes em todas as condições testadas. Apesar das diferenças marcantes em ambos os modelos experimentais, nossos achados demonstram que a acidificação e o preenchimento de vesículas sinápticas não são necessários para o tráfico normal da vesícula nas sinapses estudadas.