RESUMO
This document is the update of the Consensus published by SAP in 2014, so that no child nor adolescent is excluded from their right to health and physical activity. The periodic medical control and the school physical education are fundamental tools. As a result, of the SARS-CoV-2 pandemic, sports practice decreased dramatically. Recommendations are formulated that serve as a reference to pediatricians, members of health care teams, educational institutions, and sports at the local, regional, and national level in the preparation of the health certificate for a child or adolescent who will participate in physical or sports activities. The pediatrician will evaluate the child or adolescent knowing that to carry out a healthy life, must perform physical activities with moderate or vigorous intensity. The health certificate implies a shared responsibility between the child or adolescent and/or the responsible adult, the doctor, the physical education teachers and/or the coaches in charge.
Este documento es la actualización del consenso publicado por la Sociedad Argentina de Pediatría en 2014, para que ningún niño, niña y adolescente (NNA) del país quede excluido de su derecho a la salud y a la actividad física. El control médico periódico y la educación física en el ámbito escolar son herramientas fundamentales para ejercer estos derechos. A raíz de la pandemia del coronavirus de tipo 2 causante del síndrome respiratorio agudo grave (SARS-CoV-2, por su sigla en inglés) disminuyó de manera notable la práctica deportiva. Se formulan recomendaciones que sirvan de referencia a pediatras, integrantes de los equipos de salud, instituciones educativas y deportivas en los niveles local, regional y nacional para la elaboración de la constancia de salud de los NNA que participarán en actividades físicas y deportivas. El pediatra evaluará al NNA sabiendo que para llevar una vida saludable éste debe realizar actividades físicas de moderada a vigorosa intensidad. La Constancia de Salud implica una responsabilidad compartida entre el NNA y/o adulto responsable, el médico, los profesores de educación física y/o los entrenadores a cargo.
Assuntos
COVID-19 , Esportes , Adolescente , Adulto , Criança , Consenso , Exercício Físico , Humanos , SARS-CoV-2RESUMO
Este documento es la actualización del consenso publicado por la Sociedad Argentina de Pediatría en 2014, para que ningún niño, niña y adolescente (NNA) del país quede excluido de su derecho a la salud y a la actividad física. El control médico periódico y la educación física en el ámbito escolar son herramientas fundamentales para ejercer estos derechos. A raíz de la pandemia del coronavirus de tipo 2 causante del síndrome respiratorio agudo grave (SARS-CoV-2, por su sigla en inglés) disminuyó de manera notable la práctica deportiva. Se formulan recomendaciones que sirvan de referencia a pediatras, integrantes de los equipos de salud, instituciones educativas y deportivas en los niveles local, regional y nacional para la elaboración de la constancia de salud de los NNA que participarán en actividades físicas y deportivas. El pediatra evaluará al NNA sabiendo que para llevar una vida saludable éste debe realizar actividades físicas de moderada a vigorosa intensidad. La Constancia de Salud implica una responsabilidad compartida entre el NNA y/o adulto responsable, el médico, los profesores de educación física y/o los entrenadores a cargo.
This document is the update of the Consensus published by SAP in 2014, so that no child nor adolescent is excluded from their right to health and physical activity. The periodic medical control and the school physical education are fundamental tools. As a result, of the SARS-CoV-2 pandemic, sports practice decreased dramatically. Recommendations are formulated that serve as a reference to pediatricians, members of health care teams, educational institutions, and sports at the local, regional, and national level in the preparation of the health certificate for a child or adolescent who will participate in physical or sports activities. The pediatrician will evaluate the child or adolescent knowing that to carry out a healthy life, must perform physical activities with moderate or vigorous intensity. The health certificate implies a shared responsibility between the child or adolescent and/or the responsible adult, the doctor, the physical education teachers and/or the coaches in charge.
Assuntos
Humanos , Criança , Adolescente , Adulto , Esportes , COVID-19 , Exercício Físico , SARS-CoV-2RESUMO
Chronic stress causes morphological alterations in the hippocampus of rodents and tree shrews, including atrophy of CA3 dendrites and loss of synapses. The molecular mechanisms underlying these structural changes remain largely unknown. We have previously identified M6a as a stress responsive gene and shown that M6a is involved in filopodium/spine outgrowth and, likely, synapse formation. M6a belongs to the proteolipid protein (PLP) family, all of their members having four transmembrane domains that allow their localization at the plasma membrane. In the present work, we analyzed other members of this family, the closely related M6b as well as PLP and its splice variant DM20. We found that chronic restraint stress in mice reduces M6b and DM20, but not PLP, mRNA levels in the hippocampus. In addition, M6b and DM20, but again not PLP, induce filopodium formation in primary cultures of hippocampal neurons. Several M6b protein isoforms were studied, all of them having similar effects except for the one lacking the transmembrane domains. Our results reveal a conserved cellular function and a stress-mediated regulation among members of the proteolipid protein family, suggesting an involvement of proteolipid proteins in the stress response.
Assuntos
Hipocampo/metabolismo , Neurônios/metabolismo , Proteolipídeos/metabolismo , Estresse Psicológico/metabolismo , Animais , Células COS , Linhagem Celular Tumoral , Células Cultivadas , Chlorocebus aethiops , Doença Crônica , Modelos Animais de Doenças , Masculino , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Proteína Proteolipídica de Mielina/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Isoformas de Proteínas/metabolismo , RNA Mensageiro/metabolismo , Restrição FísicaRESUMO
Gpm6a was identified as a stress-responsive gene in the hippocampal formation. This gene is down-regulated in the hippocampus of both socially and physically stressed animals, and this effect can be reversed by antidepressant treatment. Previously we showed that the stress-regulated protein M6a is a key modulator for neurite outgrowth and filopodium/spine formation. In the present work, mutational analysis was used to characterize the action of M6a at the molecular level. We show that four cysteines 162, 174, 192, and 202 within EC2 are functionally crucial sites. The presence of cysteines 162 and 202 is essential for the efficient cell surface expression of the M6a protein. In contrast, cysteines 174 and 192, which form a disulfide bridge as shown by biochemical analysis, are not required for the efficient surface expression of M6a. Their mutation to alanine does not interfere with the localization of M6a to filopodial protrusions in primary hippocampal neurons. The neurons expressing C174A and/or C192A mutants display decreased filopodia number. In non-permeabilized cells, these mutant proteins are not recognized by a function-blocking monoclonal antibody directed to M6a. Moreover, neurons in contact with axons expressing C174A/C192A mutant display significantly lower density of presynaptic clusters over their dendrites. Taken together, this study demonstrates that cysteines in the EC2 domain are critical for the role of M6a in filopodium outgrowth and synaptogenesis.
Assuntos
Membrana Celular/metabolismo , Cisteína/genética , Hipocampo/metabolismo , Glicoproteínas de Membrana/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Estresse Fisiológico , Animais , Western Blotting , Células COS , Células Cultivadas , Chlorocebus aethiops , Cisteína/metabolismo , Hipocampo/citologia , Técnicas Imunoenzimáticas , Glicoproteínas de Membrana/genética , Mutagênese Sítio-Dirigida , Proteínas do Tecido Nervoso/genética , Ratos , Ratos Wistar/embriologiaRESUMO
BACKGROUND: Chronic stress has significant effects on hippocampal structure and function. We have previously identified nerve growth factor (NGF), membrane glycoprotein 6a (M6a), the guanine nucleotide binding protein (G protein) alpha q polypeptide (GNAQ), and CDC-like kinase 1 (CLK-1) as genes regulated by psychosocial stress and clomipramine treatment in the hippocampus of tree shrews. These genes encode proteins involved in neurite outgrowth. METHODS: To analyze whether regulation of the above-mentioned genes is conserved between different species, stressors, and antidepressant drugs, we subjected mice to repeated restraint stress and tianeptine treatment and measured hippocampal messenger RNA (mRNA) levels by real time reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Chronically stressed mice displayed a reduction in transcript levels for NGF, M6a, GNAQ, and CLK-1. In addition, other genes implicated in neuronal plasticity, such as brain-derived neurotrophic factor (BDNF), cyclic adenosine monophosphate (cAMP) response element binding protein (CREB), protein kinase C (PKC), neural cell adhesion molecule (NCAM), and synapsin I were downregulated in stressed mice. Tianeptine treatment reversed the stress effects for the genes analyzed. Alterations in gene expression were dependent on the duration of the stress treatment and, in some cases, were only observed in male mice. CONCLUSIONS: These results suggest that genes involved in neurite remodeling are one of the main targets for regulation by chronic stress. The finding that this regulation is conserved in different stress models and antidepressant treatments highlights the biological relevance of the genes analyzed and suggests that they might be involved in stress-related disorders.
Assuntos
Antidepressivos/farmacologia , Expressão Gênica/fisiologia , Genótipo , Hipocampo/patologia , Modelos Genéticos , RNA Mensageiro/genética , Estresse Psicológico/complicações , Sintenia/genética , Tiazepinas/farmacologia , Animais , Feminino , Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/genética , Expressão Gênica/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Masculino , Glicoproteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Fator de Crescimento Neural/genética , Proteínas do Tecido Nervoso/genética , Plasticidade Neuronal/efeitos dos fármacos , Plasticidade Neuronal/genética , Proteínas Serina-Treonina Quinases/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores Sexuais , Estresse Psicológico/patologia , Sintenia/efeitos dos fármacosRESUMO
Neuronal remodeling is a fundamental process by which the brain responds to environmental influences, e.g., during stress. In the hippocampus, chronic stress causes retraction of dendrites in CA3 pyramidal neurons. We have recently identified the glycoprotein M6a as a stress-responsive gene in the hippocampal formation. This gene is down-regulated in the hippocampus of both socially and physically stressed animals, and this effect can be reversed by antidepressant treatment. In the present work, we analyzed the biological function of the M6a protein. Immunohistochemistry showed that the M6a protein is abundant in all hippocampal subregions, and subcellular analysis in primary hippocampal neurons revealed its presence in membrane protrusions (filopodia/spines). Transfection experiments revealed that M6a overexpression induces neurite formation and increases filopodia density in hippocampal neurons. M6a knockdown with small interference RNA methodology showed that M6a low-expressing neurons display decreased filopodia number and a lower density of synaptophysin clusters. Taken together, our findings indicate that M6a plays an important role in neurite/filopodium outgrowth and synapse formation. Therefore, reduced M6a expression might be responsible for the morphological alterations found in the hippocampus of chronically stressed animals. Potential mechanisms that might explain the biological effects of M6a are discussed.
Assuntos
Espinhas Dendríticas/fisiologia , Hipocampo/citologia , Glicoproteínas de Membrana/fisiologia , Proteínas do Tecido Nervoso/fisiologia , Neuritos/fisiologia , Pseudópodes/fisiologia , Estresse Fisiológico/metabolismo , Animais , Células COS , Linhagem Celular Tumoral , Membrana Celular/genética , Membrana Celular/patologia , Membrana Celular/fisiologia , Células Cultivadas , Chlorocebus aethiops , Hipocampo/fisiologia , Hipocampo/fisiopatologia , Masculino , Glicoproteínas de Membrana/antagonistas & inibidores , Glicoproteínas de Membrana/biossíntese , Glicoproteínas de Membrana/genética , Camundongos , Proteínas do Tecido Nervoso/antagonistas & inibidores , Proteínas do Tecido Nervoso/biossíntese , Proteínas do Tecido Nervoso/genética , Plasticidade Neuronal/genética , Neurônios/citologia , Neurônios/metabolismo , Neurônios/fisiologia , Células PC12 , RNA Interferente Pequeno/farmacologia , Ratos , Estresse Fisiológico/patologia , Estresse Fisiológico/fisiopatologia , TransfecçãoRESUMO
Depressive disorders are among the most frequent forms of mental illness. Both genetic and environmental factors, such as stress, are involved in the etiology of depression. Therefore, chronic stress paradigms in laboratory animals constitute an important tool for research in this field. The molecular bases of chronic stress/depression are largely unknown, although a large amount of information has been accumulated during recent years. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis as well as structural and physiological alterations in the hippocampus and neocortex are known to occur. Modifications in the expression level of some genes, such as brain-derived neurotrophic factor, cAMP-response-element binding protein, serotonin receptors and HPA axis components were consistently associated in a number of experimental models. However, recent results suggest that several synaptic proteins, transcription factors and proteins involved in neuronal growth/differentiation, are also modified in their expression in experimental models of chronic stress. In general, these alterations can be reversed by treatment with antidepressants. Thus, a complex pattern of gene expression leading to stress/depression is starting to emerge. We summarize here recent findings on the alterations of gene expression in the hippocampus of chronically stressed and antidepressant treated animals.
Assuntos
Antidepressivos/farmacologia , Transtorno Depressivo/tratamento farmacológico , Transtorno Depressivo/fisiopatologia , Regulação da Expressão Gênica/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Estresse Fisiológico/fisiopatologia , Animais , Doença Crônica , Transtorno Depressivo/etiologia , Modelos Animais de Doenças , Regulação da Expressão Gênica/fisiologia , Hipocampo/metabolismo , Humanos , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/fisiopatologia , Estresse Fisiológico/complicações , Transcrição Gênica/efeitos dos fármacos , Transcrição Gênica/fisiologiaRESUMO
Adrenal corticosteroids influence the function of the hippocampus, the brain structure in which the highest expression of glucocorticoid receptors is found. Chronic high levels of cortisol elicited by stress or through exogenous administration can cause irreversible damage and cognitive deficits. In this study, we searched for genes expressed in the hippocampal formation after chronic cortisol treatment in male tree shrews. Animals were treated orally with cortisol for 28 days. At the end of the experiments, we generated two subtractive hippocampal hybridization libraries from which we sequenced 2,246 expressed sequenced tags (ESTs) potentially regulated by cortisol. To validate this approach further, we selected some of the candidate clones to measure mRNA expression levels in hippocampus using real-time PCR. We found that 66% of the sequences tested (10 of 15) were differentially represented between cortisol-treated and control animals. The complete set of clones was subjected to a bioinformatic analysis, which allowed classification of the ESTs into four different main categories: 1) known proteins or genes (approximately 28%), 2) ESTs previously published in the database (approximately 16%), 3) novel ESTs matching only the reference human or mouse genome (approximately 5%), and 4) sequences that do not match any public database (50%). Interestingly, the last category was the most abundant. Hybridization assays revealed that several of these clones are indeed expressed in hippocampal tissue from tree shrew, human, and/or rat. Therefore, we discovered an extensive inventory of new molecular targets in the hippocampus that serves as a reference for hippocampal transcriptional responses under various conditions. Finally, a detailed analysis of the genomic localization in human and mouse genomes revealed a survey of putative novel splicing variants for several genes of the nervous system.
Assuntos
Regulação da Expressão Gênica/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hidrocortisona/administração & dosagem , Animais , Clonagem Molecular/métodos , Esquema de Medicação , Etiquetas de Sequências Expressas , Perfilação da Expressão Gênica/métodos , Biblioteca Gênica , Hipocampo/fisiologia , Humanos , Hibridização In Situ/métodos , Masculino , RNA Mensageiro/biossíntese , Ratos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , TupaiidaeRESUMO
Analysis of differentially expressed genes in the brain is a promising tool for elucidating pathological mechanisms that lead to central nervous disorders. Stress is known to be involved in the development of psychopathologies such as depression. In the present study, we searched for differentially expressed genes in the hippocampal formation after chronic psychosocial stress and after treatment with the antidepressant clomipramine. Experiments were conducted in male tree shrews, a valid psychosocial stress model in which antidepressant drugs prevent diverse effects of stress. Because many effects of stress have been attributed to the stress-induced elevation in glucocorticoids, we screened two subtractive hippocampal cDNA libraries generated from RNA of chronic cortisol-treated animals. Using real-time PCR to measure mRNA amounts, we identified five sequences whose expression levels differed between stressed animals and controls. Transcript levels of four of them, nerve growth factor (NGF), membrane glycoprotein 6a (M6a), CDC-like kinase 1 (CLK-1) and G-protein alpha q (GNAQ) were reduced by chronic psychosocial stress. Reduced amounts of these genes, which are all related to processes of cell differentiation, is in agreement with previous findings showing a retraction of dendrites and an impairment of neurogenesis in the hippocampal formation after chronic stress. An additional expressed sequence that was also regulated by stress could not be assigned to any known gene. Treatment with the antidepressant clomipramine prevented stress effects on expression of M6a, CLK-1, GNAQ and the novel sequence, but showed no effect on NGF stress-induced down-regulation. These findings support the concept that depressive disorders are accompanied by processes of neuronal dedifferentiation, at least in the hippocampal formation, and that antidepressants prevent these processes.
Assuntos
Antidepressivos/farmacologia , Clomipramina/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Estresse Psicológico/genética , Animais , Antidepressivos/uso terapêutico , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteínas de Caenorhabditis elegans , ATPases Transportadoras de Cálcio/genética , ATPases Transportadoras de Cálcio/metabolismo , Proteínas de Transporte de Cátions , Clomipramina/uso terapêutico , Clonagem Molecular/métodos , Ciclofilinas/genética , Ciclofilinas/metabolismo , Ensaio de Imunoadsorção Enzimática , Subunidades alfa de Proteínas de Ligação ao GTP/genética , Subunidades alfa de Proteínas de Ligação ao GTP/metabolismo , Hipocampo/metabolismo , Hibridização In Situ , Masculino , Glicoproteínas de Membrana , Fator de Crescimento Neural/genética , Fator de Crescimento Neural/metabolismo , Proteínas do Tecido Nervoso , ATPases Transportadoras de Cálcio da Membrana Plasmática , RNA Mensageiro/biossíntese , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Proteínas Ribossômicas/genética , Proteínas Ribossômicas/metabolismo , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/metabolismo , TupaiidaeRESUMO
In mammals, gene transcription is a step subjected to tight regulation mechanisms. In fact, changes in mRNA levels in the central nervous system (CNS) can account for numerous phenotypic differences in brain function. We performed a high-resolution analysis of mRNA expression levels for 37 genes selected from a normal rat hippocampus cDNA library. mRNA amounts were quantified using a Real Time PCR SYBR Green assay. We found that, in general, individuals from an inbred rat population (n = 20) have shown 2-3 times differences in the basal level of expression of the genes analyzed. Up to several fold differences among individuals were observed for certain genes. These inter-individual differences were obtained after correction for the different amounts of mRNA in each sample. Power calculations were performed to determine the number of individuals required to detect reliable differences in expression levels between a control and an experimental group. These data indicated that, depending on the variability of the candidate gene selected, it was necessary to analyze from five to 135 individuals in each group to detect differences of 50% in the levels of mRNA expression between two groups investigated. The comparison of mRNA abundance from different genes revealed a wide range of expression levels for the 37 genes, showing a 26,000-fold difference between the highest and lowest expressed gene.