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1.
Proc Natl Acad Sci U S A ; 117(6): 3254-3260, 2020 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-32001507

RESUMO

The giant Mauthner (M) cell is the largest neuron known in the vertebrate brain. It has enabled major breakthroughs in neuroscience but its ultimate function remains surprisingly unclear: An actual survival value of M cell-mediated escapes has never been supported experimentally and ablating the cell repeatedly failed to eliminate all rapid escapes, suggesting that escapes can equally well be driven by smaller neurons. Here we applied techniques to simultaneously measure escape performance and the state of the giant M axon over an extended period following ablation of its soma. We discovered that the axon survives remarkably long and remains still fully capable of driving rapid escape behavior. By unilaterally removing one of the two M axons and comparing escapes in the same individual that could or could not recruit an M axon, we show that the giant M axon is essential for rapid escapes and that its loss means that rapid escapes are also lost forever. This allowed us to directly test the survival value of the M cell-mediated escapes and to show that the absence of this giant neuron directly affects survival in encounters with a natural predator. These findings not only offer a surprising solution to an old puzzle but demonstrate that even complex brains can trust vital functions to individual neurons. Our findings suggest that mechanisms must have evolved in parallel with the unique significance of these neurons to keep their axons alive and connected.


Assuntos
Reação de Fuga/fisiologia , Sistema Nervoso/crescimento & desenvolvimento , Neurônios/citologia , Neurônios/fisiologia , Animais , Axônios/fisiologia , Embrião não Mamífero/fisiologia , Larva/fisiologia , Peixe-Zebra
2.
PLoS Comput Biol ; 16(1): e1007602, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31895942

RESUMO

A central problem of neuroscience involves uncovering the principles governing the organization of nervous systems which ensure robustness in brain development. The nematode Caenorhabditis elegans provides us with a model organism for studying this question. In this paper, we focus on the invariant connection structure and spatial arrangement of the neurons comprising the somatic neuronal network of this organism to understand the key developmental constraints underlying its design. We observe that neurons with certain shared characteristics-such as, neural process lengths, birth time cohort, lineage and bilateral symmetry-exhibit a preference for connecting to each other. Recognizing the existence of such homophily and their relative degree of importance in determining connection probability within neurons (for example, in synapses, symmetric pairing is the most dominant factor followed by birth time cohort, process length and lineage) helps in connecting specific neuronal attributes to the topological organization of the network. Further, the functional identities of neurons appear to dictate the temporal hierarchy of their appearance during the course of development. Providing crucial insights into principles that may be common across many organisms, our study shows how the trajectory in the developmental landscape constrains the structural organization of a nervous system.


Assuntos
Caenorhabditis elegans/crescimento & desenvolvimento , Caenorhabditis elegans/fisiologia , Modelos Neurológicos , Sistema Nervoso/crescimento & desenvolvimento , Neurogênese/fisiologia , Animais , Biologia Computacional , Neurônios/fisiologia
3.
PLoS One ; 14(10): e0223427, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31600248

RESUMO

CONTEXT: Whether all degrees of periventricular leukomalacia (PVL) and peri-intraventricular haemorrhage (PIVH) have a negative impact on neurodevelopment. OBJECTIVE: To determine the impact of PVL and PIVH in the incidence of cerebral palsy, sensorineural impairment and development scores in preterm neonates. Registered in PROSPERO (CRD42017073113). DATA SOURCES: PubMed, Embase, SciELO, LILACS, and Cochrane databases. STUDY SELECTION: Prospective cohort studies evaluating neurodevelopment in children born preterm which performed brain imaging in the neonatal period. DATA EXTRACTION: Two independent researchers extracted data using a predesigned data extraction sheet. STATISTICAL METHODS: A random-effects model was used, with Mantel-Haenszel approach and a Sidik-Jonkman method for the estimation of variances, combined with Hartung-Knapp-Sidik-Jonkman correction. Heterogeneity was assessed through the I2 statistic and sensitivity analysis were performed when possible. No funnel plots were generated but publication bias was discussed as a possible limitation. RESULTS: Our analysis concluded premature children with any degree of PIVH are at increased risk for cerebral palsy (CP) when compared to children with no PIVH (3.4, 95% CI 1.60-7.22; 9 studies), a finding that persisted on subgroup analysis for studies with mean birth weight of less than 1000 grams. Similarly, PVL was associated with CP, both in its cystic (19.12, 95% CI 4.57-79.90; 2 studies) and non-cystic form (9.27, 95% CI 5.93-14.50; 2 studies). We also found children with cystic PVL may be at risk for visual and hearing impairment compared to normal children, but evidence is weak. LIMITATIONS: Major limitations were the lack of data for PVL in general, especially for the outcome of neurodevelopment, the high heterogeneity among methods used to assess neurodevelopment and the small number of studies, which led to meta-analysis with high heterogeneity and wide confidence intervals. CONCLUSIONS: There was no evidence supporting the hypothesis that PIVH causes impairment in neuropsychomotor development in our meta-analysis, but review of newer studies show an increased risk for lower intelligence scores in children with severe lesions, both PIVH and PVL. There is evidence to support the hypothesis that children with any degree of PIVH, especially those born below 1000 grams and those with severe haemorrhage, are at increased risk of developing CP, as well as children with PVL, both cystic and non-cystic.


Assuntos
Hemorragia Cerebral/complicações , Recém-Nascido Prematuro/crescimento & desenvolvimento , Leucomalácia Periventricular/complicações , Sistema Nervoso/crescimento & desenvolvimento , Perda Auditiva/complicações , Humanos , Recém-Nascido , Resultado do Tratamento , Transtornos da Visão/complicações
4.
Sci Adv ; 5(9): eaax5858, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31535028

RESUMO

Annelid worms are a disparate, primitively segmented clade of bilaterians that first appear during the early Cambrian Period. Reconstructing their early evolution is complicated by the extreme morphological diversity in early diverging lineages, rapid diversification, and sparse fossil record. Canadia spinosa, a Burgess Shale fossil polychaete, is redescribed as having palps with feeding grooves, a dorsal median antenna and biramous parapodia associated with the head and flanking a ventral mouth. Carbonaceously preserved features are identified as a terminal brain, circumoral connectives, a midventral ganglionated nerve cord and prominent parapodial nerves. Phylogenetic analysis recovers neuroanatomically simple extant taxa as the sister group of other annelids, but the phylogenetic position of Canadia suggests that the annelid ancestor was reasonably complex neuroanatomically and that reduction of the nervous system occurred several times independently in the subsequent 500 million years of annelid evolution.


Assuntos
Evolução Biológica , Fósseis/anatomia & histologia , Sistema Nervoso/anatomia & histologia , Poliquetos/anatomia & histologia , Poliquetos/classificação , Animais , Comportamento Alimentar , Sistema Nervoso/crescimento & desenvolvimento , Filogenia
5.
J Morphol ; 280(11): 1628-1650, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31487090

RESUMO

Sipuncula is a clade of unsegmented marine worms that are currently placed among the basal radiation of conspicuously segmented Annelida. Their new location provides a unique opportunity to reinvestigate the evolution and development of segmented body plans. Neural segmentation is clearly evident during ganglionic ventral nerve cord (VNC) formation across Sedentaria and Errantia, which includes the majority of annelids. However, recent studies show that some annelid taxa outside of Sedentaria and Errantia have a medullary cord, without ganglia, as adults. Importantly, neural development in these taxa is understudied and interpretation can vary widely. For example, reports in sipunculans range from no evidence of segmentation to vestigial segmentation as inferred from a few pairs of serially repeated neuronal cell bodies along the VNC. We investigated patterns of pan-neuronal, neuronal subtype, and axonal markers using immunohistochemistry and whole mount in situ hybridization (WMISH) during neural development in an indirect-developing sipunculan, Themiste lageniformis. Confocal imaging revealed two clusters of 5HT+ neurons, two pairs of FMRF+ neurons, and Tubulin+ peripheral neurites that appear to be serially positioned along the VNC, similar to other sipunculans, to other annelids, and to spiralian taxa outside of Annelida. WMISH of a synaptotagmin1 ortholog in T. lageniformis (Tl-syt1) showed expression throughout the centralized nervous system (CNS), including the VNC where it appears to correlate with mature 5HT+ and FMRF+ neurons. An ortholog of elav1 (Tl-elav1) showed expression in differentiated neurons of the CNS with continuous expression in the VNC, supporting evidence of a medullary cord, and refuting evidence of ontogenetic segmentation during formation of the nervous system. Thus, we conclude that sipunculans do not exhibit any signs of morphological segmentation during development.


Assuntos
Larva/crescimento & desenvolvimento , Sistema Nervoso/crescimento & desenvolvimento , Neurogênese , Poliquetos/crescimento & desenvolvimento , Animais , Regulação da Expressão Gênica no Desenvolvimento , Larva/anatomia & histologia , Microscopia Confocal , Sistema Nervoso/anatomia & histologia , Neurônios , Poliquetos/anatomia & histologia , Poliquetos/genética
7.
Am J Physiol Endocrinol Metab ; 317(4): E617-E630, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31361544

RESUMO

Disturbances of diet during pregnancy and early postnatal life may impact colonization of gut microbiota during early life, which could influence infant health, leading to potential long-lasting consequences later in life. This is a nonsystematic review that explores the recent scientific literature to provide a general perspective of this broad topic. Several studies have shown that gut microbiota composition is related to changes in metabolism, energy balance, and immune system disturbances through interaction between microbiota metabolites and host receptors by the gut-brain axis. Moreover, recent clinical studies suggest that an intestinal dysbiosis in gut microbiota may result in cognitive disorders and behavioral problems. Furthermore, recent research in the field of brain imaging focused on the study of the relationship between gut microbial ecology and large-scale brain networks, which will help to decipher the influence of the microbiome on brain function and potentially will serve to identify multiple mediators of the gut-brain axis. Thus, knowledge about optimal nutrition by modulating gut microbiota-brain axis activity will allow a better understanding of the molecular mechanisms involved in the crosstalk between gut microbiota and the developing brain during critical windows. In addition, this knowledge will open new avenues for developing novel microbiota-modulating based diet interventions during pregnancy and early life to prevent metabolic disorders, as well as neurodevelopmental deficits and brain functional disorders.


Assuntos
Bactérias/metabolismo , Encéfalo/fisiologia , Microbioma Gastrointestinal/fisiologia , Sistema Imunitário/fisiologia , Fígado/fisiologia , Sistema Nervoso/crescimento & desenvolvimento , Animais , Humanos
8.
Elife ; 82019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-31264582

RESUMO

Sexual maturation must occur on a controlled developmental schedule. In mammals, Makorin3 (MKRN3) and the miRNA regulators LIN28A/B are key regulators of this process, but how they act is unclear. In C. elegans, sexual maturation of the nervous system includes the functional remodeling of postmitotic neurons and the onset of adult-specific behaviors. Here, we find that the lin-28-let-7 axis (the 'heterochronic pathway') determines the timing of these events. Upstream of lin-28, the Makorin lep-2 and the lncRNA lep-5 regulate maturation cell-autonomously, indicating that distributed clocks, not a central timer, coordinate sexual differentiation of the C. elegans nervous system. Overexpression of human MKRN3 delays aspects of C. elegans sexual maturation, suggesting the conservation of Makorin function. These studies reveal roles for a Makorin and a lncRNA in timing of sexual differentiation; moreover, they demonstrate deep conservation of the lin-28-let-7 system in controlling the functional maturation of the nervous system.


Assuntos
Proteínas de Caenorhabditis elegans/genética , Caenorhabditis elegans/genética , RNA Longo não Codificante/genética , Proteínas Repressoras/genética , Ribonucleoproteínas/genética , Animais , Caenorhabditis elegans/crescimento & desenvolvimento , Diferenciação Celular , Regulação da Expressão Gênica no Desenvolvimento , Humanos , MicroRNAs , Mutação , Sistema Nervoso/crescimento & desenvolvimento , Maturidade Sexual/genética
9.
Cell Mol Life Sci ; 76(16): 3055-3081, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31236626

RESUMO

'A disintegrin and metalloproteases' (ADAMs) are a family of transmembrane proteins with diverse functions in multicellular organisms. About half of the ADAMs are active metalloproteases and cleave numerous cell surface proteins, including growth factors, receptors, cytokines and cell adhesion proteins. The other ADAMs have no catalytic activity and function as adhesion proteins or receptors. Some ADAMs are ubiquitously expressed, others are expressed tissue specifically. This review highlights functions of ADAMs in the mammalian nervous system, including their links to diseases. The non-proteolytic ADAM11, ADAM22 and ADAM23 have key functions in neural development, myelination and synaptic transmission and are linked to epilepsy. Among the proteolytic ADAMs, ADAM10 is the best characterized one due to its substrates Notch and amyloid precursor protein, where cleavage is required for nervous system development or linked to Alzheimer's disease (AD), respectively. Recent work demonstrates that ADAM10 has additional substrates and functions in the nervous system and its substrate selectivity may be regulated by tetraspanins. New roles for other proteolytic ADAMs in the nervous system are also emerging. For example, ADAM8 and ADAM17 are involved in neuroinflammation. ADAM17 additionally regulates neurite outgrowth and myelination and its activity is controlled by iRhoms. ADAM19 and ADAM21 function in regenerative processes upon neuronal injury. Several ADAMs, including ADAM9, ADAM10, ADAM15 and ADAM30, are potential drug targets for AD. Taken together, this review summarizes recent progress concerning substrates and functions of ADAMs in the nervous system and their use as drug targets for neurological and psychiatric diseases.


Assuntos
Proteínas ADAM/metabolismo , Sistema Nervoso/metabolismo , Proteínas ADAM/química , Animais , Transporte Biológico , Epilepsia/metabolismo , Epilepsia/patologia , Humanos , Inflamação/metabolismo , Inflamação/patologia , Bainha de Mielina/fisiologia , Sistema Nervoso/crescimento & desenvolvimento , Canais de Potássio/metabolismo , Proteólise
10.
PLoS One ; 14(6): e0218887, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31233553

RESUMO

INTRODUCTION: Aggressive nutritional strategy, particularly enhancing early provision of energy and protein, has appeared to reduce postnatal growth failure and improve later developmental outcomes. But the amount of macronutrients required remains unclear. The aim of this study was to investigate the impact of protein and energy intakes during the first two weeks after birth on neurodevelopmental outcomes. METHODS: This retrospective cohort study of very low birth weight infants born between January 2012 and December 2015 was conducted at one tertiary neonatal intensive care unit. The primary outcome was a neurodevelopmental impairment (NDI) at 2 years corrected age defined by a cerebral palsy or a 24 month Ages and Stages Questionnaires score on any of the five domains lower than 2 standard deviation below the mean score. Multivariable logistic regression analysis was used to adjust for perinatal and postnatal confounders. RESULTS: Among 245 (73%) infants discharged home alive, 159 (65%) had follow-up at 2 years. Infants with NDI (55/159, 35%) were more likely male gender (67.3% versus 46.2%, P = 0.02) and experienced more patent ductus arteriosus (PDA) ligation (20% versus 5.8%, P = 0.01) than control. After adjusting for confounders, first-week protein intake (OR: 2.27 [CI: 1.07-5.14]; P < 0.05), second-week non-protein energy intake (OR: 1.03 [CI: 1.01-1.05]; P < 0.01) and PDA ligation (OR: 6.81 [1.80-28.46]; P < 0.01) had significant independent association with higher likelihood of NDI at 2 years. CONCLUSION: Providing nutrition above the optimal level may not be beneficial and may even be harmful. These results confirm the recent recommendation to decrease amino acid intakes published in the latest ESPGHAN guidelines.


Assuntos
Ingestão de Energia/fisiologia , Recém-Nascido de muito Baixo Peso/crescimento & desenvolvimento , Sistema Nervoso/crescimento & desenvolvimento , Proteínas/administração & dosagem , Pré-Escolar , Permeabilidade do Canal Arterial/fisiopatologia , Feminino , Seguimentos , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Ligadura , Masculino , Estudos Retrospectivos
11.
Fertil Steril ; 111(6): 1047-1053, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31155114

RESUMO

Monitoring the safety of intracytoplasmic sperm injection (ICSI) has been impeded by uncertainties regarding the extent to which offspring health is influenced by paternal characteristics linked to male infertility or the processes that ICSI treatment entails. Few studies examining long-term health and developmental outcomes in children conceived with ICSI have considered the influence of paternal infertility adequately. In the available literature, large population-based studies suggest underlying male factors, and the severity of male factor infertility, increase the risk of mental retardation and autism in offspring, as does the ICSI procedure itself, but these findings have not been replicated consistently. Robust evidence of the influence of male factors on other health outcomes is lacking, with many studies limited by sample size. Nevertheless, emerging evidence suggests children conceived with ICSI have increased adiposity, particularly girls. Further, young men conceived with ICSI may have impaired spermatogenesis; the mechanisms underlying this remain unclear, with inconclusive evidence of inheritance of Y chromosome microdeletions. The current inconsistent and often sparse literature concerning the long-term health of children conceived with ICSI, and the specific influence of male infertility factors, underscore the need for concerted monitoring of children conceived with this technique across the lifespan. With the rapid expansion of use of ICSI for non-male factors, sufficiently large studies that compare outcomes between groups conceived with this technique for male factors versus non-male factors will provide critical evidence to elucidate the intergenerational impact of male infertility.


Assuntos
Comportamento Infantil , Desenvolvimento Infantil , Saúde da Criança , Filho de Pais Incapacitados , Fertilidade , Infertilidade Masculina/terapia , Injeções de Esperma Intracitoplásmicas , Adiposidade , Adulto , Fatores Etários , Estatura , Criança , Pré-Escolar , Cognição , Feminino , Nível de Saúde , Humanos , Lactente , Comportamento do Lactente , Infertilidade Masculina/epidemiologia , Infertilidade Masculina/fisiopatologia , Masculino , Sistema Nervoso/crescimento & desenvolvimento , Gravidez , Medição de Risco , Fatores de Risco , Injeções de Esperma Intracitoplásmicas/efeitos adversos , Resultado do Tratamento , Ganho de Peso
12.
Fertil Steril ; 111(6): 1076-1091, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31155115

RESUMO

Fetal programming may influence childhood and adult life, determining the risk of specific diseases. During earlier stages of pregnancy, the transfer of maternal thyroid hormones to the fetus is vital for adequate neurologic development. The presence of severe maternal thyroid dysfunction, particularly severe iodine deficiency, is devastating, leading to irreversible neurologic sequelae. Moreover, mild maternal thyroid conditions, such as a mild-to-moderate iodine deficiency, may also lead to milder neurologic and behavioral conditions later during the life of the offspring. Maternal dysglycemia due to pregestational or gestational diabetes mellitus is another common situation in which fetal development encounters a hostile environment. Hyperglycemia in utero may trigger metabolic conditions in the offspring, including abnormalities of glucose tolerance and weight excess. Physicians assisting pregnant women have to be aware about these conditions, because they may go unnoticed if not properly screened. Because an early diagnosis and appropriate management may prevent most of the possible negative consequences for the progeny, the prevention, early diagnosis, and proper management of these endocrine conditions should be offered to all women undergoing pregnancy. Here, we comprehensively review the current evidence about the effects of maternal thyroid dysfunction and maternal dysglycemia on the cognitive function and carbohydrate metabolism in the offspring, two prevalent conditions of utmost importance for the child's health and development.


Assuntos
Saúde da Criança , Filho de Pais Incapacitados , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/complicações , Diabetes Gestacional , Sistema Endócrino/fisiopatologia , Efeitos Tardios da Exposição Pré-Natal , Doenças da Glândula Tireoide/complicações , Fatores Etários , Criança , Comportamento Infantil , Desenvolvimento Infantil , Pré-Escolar , Cognição , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/fisiopatologia , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus Tipo 2/terapia , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/fisiopatologia , Diabetes Gestacional/terapia , Suscetibilidade a Doenças , Metabolismo Energético , Feminino , Nível de Saúde , Humanos , Lactente , Recém-Nascido , Masculino , Saúde Materna , Sistema Nervoso/crescimento & desenvolvimento , Gravidez , Medição de Risco , Fatores de Risco , Doenças da Glândula Tireoide/diagnóstico , Doenças da Glândula Tireoide/fisiopatologia , Doenças da Glândula Tireoide/terapia
13.
Ecotoxicol Environ Saf ; 180: 762-769, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31154201

RESUMO

Alkyl phenanthrene (A-Phen) and Dechlorane Plus (DP) are ubiquitous environmental pollutants that widely co-exist in the environment. It has been established that both A-Phen and DP elicit neurotoxicity, but the potential interactive toxicity of these contaminants is not well-known. To determine whether a mixture of A-Phen and DP would exhibit interactive effects on neurodevelopment, we co-exposed 3-methylphenanthrene (3-MP), a representative of A-Phen, with DP. Our results illustrated that exposure to 5 or 20 µg/L 3-MP alone or in combination with 60 µg/L DP caused neurobehavioral anomalies in zebrafish. In accordance with the behavioral deficits, 3-MP alone or co-exposed with DP significantly decreased axonal growth of secondary motoneurons, altered intracellular Ca2+ homeostasis and induced cell apoptosis in the muscle of zebrafish. Additionally, 3-MP alone or co-exposed with DP significantly increased reactive oxygen species (ROS) and the mRNA levels of apoptosis-related genes. These findings indicate that 3-MP alone or co-exposed with DP induces neurobehavioral deficits through the combined effects on neuronal connectivity and muscle function. Chemical analysis revealed significant increases in 3-MP and DP bioaccumulation in zebrafish co-exposed with 3-MP and DP. Elevated bioaccumulation resulting from mixture exposure may represent a significant contribution of the synergistic effects observed in combined chemical exposure.


Assuntos
Hidrocarbonetos Clorados/toxicidade , Sistema Nervoso/efeitos dos fármacos , Fenantrenos/toxicidade , Compostos Policíclicos/toxicidade , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/fisiologia , Animais , Proteínas Reguladoras de Apoptose/genética , Sinergismo Farmacológico , Sistema Nervoso/crescimento & desenvolvimento , Fenantrenos/síntese química , RNA Mensageiro/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Peixe-Zebra/crescimento & desenvolvimento
14.
Environ Sci Pollut Res Int ; 26(18): 18267-18290, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31041704

RESUMO

Exposure to pesticides is a major factor in the cause of dysfunction in the nervous system and neurodevelopment disorders in children at critical periods of great vulnerability. The aim of this study was to review scientific evidence published on neurodevelopmental effects of prenatal and postnatal exposure to organophosphate pesticides (OPs) in different stages, including neonates, infants, toddlers, preschool children, and school-age children. Full-text articles published in PubMed, Scopus, and ISI databases between 1973 and 2019 were reviewed and the scientific evidence was evaluated. Results: Fifty studies were eligible for inclusion in this quantitative synthesis. Fifteen of these papers evaluated the effects on neonates and infants, 18 on the effects on toddlers and preschool children, and 24 the effects on school-age children. Considerable evidence suggests that prenatal exposure to OPs contributes to child neurodevelopment disorders in all stages, whereas data about the effects of postnatal exposure are limited. Therefore, the available evidence supports the theory that sensitive time-windows occur prenatally rather than postnatally. Although 45 out of the total 50 selected articles found an association between OP exposure and child neurodevelopment, some of the evidence is controversial. A standardized methodology is needed to enable the comparison of the results in several studies, and further research studies are needed to warrant firmer conclusions. A systematic review of this evidence should be performed continuously to update the state of knowledge regarding neurodevelopmental effects associated with OP exposure.


Assuntos
Poluentes Ambientais/toxicidade , Sistema Nervoso/efeitos dos fármacos , Organofosfatos/toxicidade , Praguicidas/toxicidade , Adolescente , Criança , Desenvolvimento Infantil/efeitos dos fármacos , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Sistema Nervoso/crescimento & desenvolvimento , Praguicidas/farmacologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal
15.
Dev Neurobiol ; 79(5): 497-517, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31102334

RESUMO

Mathematical and computational modeling enables biologists to integrate data from observations and experiments into a theoretical framework. In this review, we describe how developmental processes associated with stem-cell-driven growth of tissue in both the embryonic and adult nervous system can be modeled using cellular automata (CA). A cellular automaton is defined by its discrete nature in time, space, and state. The discrete space is represented by a uniform grid or lattice containing agents that interact with other agents within their local neighborhood. This possibility of local interactions of agents makes the cellular automata approach particularly well suited for studying through modeling how complex patterns at the tissue level emerge from fundamental developmental processes (such as proliferation, migration, differentiation, and death) at the single-cell level. As part of this review, we provide a primer for how to define biologically inspired rules governing these processes so that they can be implemented into a CA model. We then demonstrate the power of the CA approach by presenting simulations (in the form of figures and movies) based on building models of three developmental systems: the formation of the enteric nervous system through invasion by neural crest cells; the growth of normal and tumorous neurospheres induced by proliferation of adult neural stem/progenitor cells; and the neural fate specification through lateral inhibition of embryonic stem cells in the neurogenic region of Drosophila.


Assuntos
Modelos Neurológicos , Sistema Nervoso/crescimento & desenvolvimento , Células-Tronco Neurais , Animais , Fenômenos Fisiológicos Celulares , Simulação por Computador , Drosophila , Sistema Nervoso/citologia , Células-Tronco Neurais/citologia , Células-Tronco Neurais/fisiologia , Neurogênese/fisiologia
16.
Environ Pollut ; 251: 538-546, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31108286

RESUMO

Chlorpyrifos (CPF), an organophosphate insecticide, has been linked to adverse neurodevelopmental effects in animal studies. However, little is known about long-term neurotoxicity of early-life CPF exposure in humans. We aimed to evaluate the associations of both prenatal and early childhood CPF exposure with neurodevelopment of children. In this observational study based on Sheyang Mini Birth Cohort, pregnant women were recruited from an agricultural region between June 2009 and January 2010, and their children were followed up from birth to age three. Urinary 3,5,6-Trichloro-2-pyridinol (TCPy), a specific metabolite of CPF, was quantified using large-volume-injection gas chromatography-tandem mass spectrometry. Developmental quotients (DQs) of children in motor, adaptive, language, and social areas were assessed by trained pediatricians. Data from 377 mother-child pairs were used in the current study. Associations between CPF exposure and neurodevelopmental indicators were estimated using generalized linear models with adjustment for potential confounders. The median concentrations of TCPy in maternal and children's urine were 5.39 µg/L and 5.34 µg/L, respectively. No statistically significant association was found between maternal urinary TCPy concentrations and children neurodevelopment. While for postnatal exposure, we found lower motor area DQ score 0.61 [95% confidence interval (CI): -1.13, -0.09; p = 0.02] and social area DQ score 0.55 (95% CI: -1.07, -0.03; p = 0.04) per one-unit increase in the ln-transformed childhood urinary TCPy concentrations. Further stratification by sex indicated that the inverse associations were only observed in boys, but not in girls. Our findings suggest that adverse neurodevelopmental effects were associated with early childhood CPF exposure, but not prenatal exposure. Additional longitudinal studies are needed to replicate these results and to further understand the toxicological mechanisms of CPF.


Assuntos
Comportamento Infantil/efeitos dos fármacos , Clorpirifos/toxicidade , Exposição Ambiental/efeitos adversos , Inseticidas/toxicidade , Sistema Nervoso/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Adulto , Criança , Pré-Escolar , China , Clorpirifos/urina , Feminino , Humanos , Inseticidas/urina , Estudos Longitudinais , Masculino , Sistema Nervoso/embriologia , Sistema Nervoso/crescimento & desenvolvimento , Gravidez , Efeitos Tardios da Exposição Pré-Natal/urina , Estudos Prospectivos , Piridonas/urina , Fatores Sexuais , Inquéritos e Questionários
17.
Nat Commun ; 10(1): 2113, 2019 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-31068592

RESUMO

Gene editing by CRISPR/Cas9 is commonly used to generate germline mutations or perform in vitro screens, but applicability for in vivo screening has so far been limited. Recently, it was shown that in Drosophila, Cas9 expression could be limited to a desired group of cells, allowing tissue-specific mutagenesis. Here, we thoroughly characterize tissue-specific (ts)CRISPR within the complex neuronal system of the Drosophila mushroom body. We report the generation of a library of gRNA-expressing plasmids and fly lines using optimized tools, which provides a valuable resource to the fly community. We demonstrate the application of our library in a large-scale in vivo screen, which reveals insights into developmental neuronal remodeling.


Assuntos
Animais Geneticamente Modificados/genética , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas/genética , Drosophila/genética , Edição de Genes/métodos , Animais , Sistemas CRISPR-Cas/genética , Feminino , Masculino , Corpos Pedunculados/metabolismo , Mutagênese , Sistema Nervoso/crescimento & desenvolvimento , Plasticidade Neuronal/genética , Neurônios/fisiologia , Plasmídeos/genética , RNA Guia/genética
18.
Biol Bull ; 236(2): 75-87, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30933639

RESUMO

The bilaterally symmetrical, feeding larval stage is an ancestral condition in echinoderms. However, many echinoderms have evolved abbreviated development and form a pentamerous juvenile without a feeding larva. Abbreviated development with a non-feeding vitellaria larva is found in five families of brittle stars, but very little is known about this type of development. In this study, the external anatomy, ciliary bands, neurons, and muscles were examined in the development of the brooded vitellaria larva of Ophioplocus esmarki. The external morphology throughout development shows typical vitellaria features, including morphogenetic movements to set up the vitellaria body plan, an anterior preoral lobe, a posterior lobe, transverse ciliary bands, and development of juvenile structures on the mid-ventral side. An early population of neurons forms at the base of the preoral lobe at the pre-vitellaria stage after the initial formation of the coelomic cavities. These early neurons may be homologous to the apical neurons that develop in echinoderms with feeding larval forms. Neurons form close to the ciliary bands, but the vitellaria larva lacks the tracts of neurons associated with the ciliary bands found in echinoderms with feeding larvae. Additional neurons form in association with the axial complex and persist into the juvenile stage. Juvenile nerves and muscles form with pentamerous symmetry in the late vitellaria stage in a manner similar to their development within the late ophiopluteus larva. Even though O. esmarki is a brooding brittle star, its developmental sequence retains the general vitellaria shape and structure; however, the vitellaria larvae are unable to swim in the water column.


Assuntos
Estrelas-do-Mar/crescimento & desenvolvimento , Animais , Padronização Corporal , Larva/anatomia & histologia , Larva/crescimento & desenvolvimento , Morfogênese , Desenvolvimento Muscular , Sistema Nervoso/crescimento & desenvolvimento , Estrelas-do-Mar/anatomia & histologia
19.
Neurotoxicology ; 73: 199-212, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31004626

RESUMO

BACKGROUND: Phthalate have been detected widely in the environment; while several studies have indicated that prenatal phthalate exposure has adverse effects on neurodevelopment, the results were inconsistent. OBJECTIVE: We aimed to determine the current research status of the relationship between prenatal exposure to different types of phthalate and cognition and behavioral development in children. We conducted a systematic review to evaluate the current state of knowledge. METHODS: We systematically searched PubMed, Web of Science, and EMBASE electronic databases up to May 2018 with manual searches of the references of retrieved publications and relevant reviews. Only birth cohort studies that reported on the association between phthalate exposure and cognitive or behavioral development were included in this review. We evaluated the risk of bias for each of the included studies using a modified instrument based on the Cochrane Collaboration's "Risk of Bias" tool. RESULT: Twenty-six birth cohort studies met our inclusion criteria, nine of which investigated the impact of phthalate exposure during pregnancy on cognition, 13 on neurobehavior, and 4 on both cognition and neurobehavior. However, ten articles reported that the effect of prenatal exposure to phthalates on cognitive development was statistically significant, 15 articles reported that the effect of prenatal exposure to phthalates on neurobehavior was statistically significant. The effect of prenatal phthalate exposure on neurodevelopment differed according to sex, but the results are inconsistent, for instance, among the five studies investigating the association between mental development index (MDI) and Mono-n-butyl phthalate (MnBP), two of them showed a significantly decreasing MDI scores with increasing concentrations of MnBP among girls, but among boys one study showed the inverse association, another showed the positive association. CONCLUSION: Di(2-ethylhexyl) phthalate, dibutyl phthalate, butyl-benzyl phthalate and di-ethyl phthalate exposure during pregnancy was associated with lower cognitive scores and worse behavior in offspring, and sex-specific effects on cognitive, psychomotor, and behavioral development were identified, especially the impact of phthalate exposure on neurobehavior in boys.


Assuntos
Comportamento Infantil/efeitos dos fármacos , Desenvolvimento Infantil/efeitos dos fármacos , Cognição/efeitos dos fármacos , Disruptores Endócrinos/efeitos adversos , Sistema Nervoso/efeitos dos fármacos , Síndromes Neurotóxicas/etiologia , Ácidos Ftálicos/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal , Fatores Etários , Criança , Pré-Escolar , Feminino , Idade Gestacional , Humanos , Lactente , Comportamento do Lactente/efeitos dos fármacos , Recém-Nascido , Masculino , Sistema Nervoso/crescimento & desenvolvimento , Síndromes Neurotóxicas/fisiopatologia , Síndromes Neurotóxicas/psicologia , Gravidez , Desempenho Psicomotor , Medição de Risco , Fatores de Risco , Fatores Sexuais
20.
Soins Pediatr Pueric ; 40(307): 8-11, 2019.
Artigo em Francês | MEDLINE | ID: mdl-30910079

RESUMO

Research in cognitive neurosciences has developed significantly and has enabled the mechanisms of neuroplasticity to be studied in order to understand the effect of music practice. In children, this research concerns mainly the impact of music learning in the setting of a music conservatory. Moreover, recent studies have also sought to measure the clinical benefits of music interventions on hospital wards, providing a scientific basis to these practices.


Assuntos
Música , Sistema Nervoso/crescimento & desenvolvimento , Criança , Neurociência Cognitiva , Humanos , Pesquisa
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