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Executive functions (EFs) are a set of cognitive processes that enable individuals to manage and coordinate their thoughts and actions toward achieving specific goals. EFs include planning, organizing, initiating, and monitoring actions, and have been found to improve with age due to the maturation of the brain, especially during childhood. Therefore, our correlational study sought to determine the relationship between the performance in executive functions and age in 79 children (36 girls, 45.6%) throughout development, between the ages of 6 and 12 (mean = 9.25; SD = 2.05), using a battery designed in Chile: BEFE (Batería de Evaluación de las Funciones Ejecutivas: Executive Function Assessment Battery) based on traditional neuropsychological tests to evaluate Working Memory, Inhibitory Control, Cognitive Flexibility, and Planning skills. Our results showed various correlations between the variables age and performance in various behavioral parameters, demonstrating an increase in the number of correct responses (positive correlation) and/or a decrease in errors (negative correlation) with age (6-12) in the subtests that correspond to dimensions of Cognitive Flexibility (Semantic and Phonological Fluency, Card Sorting Game, and Tracing Tasks), Inhibitory Control (ENA-F and Sentence Completion), Working Memory (Audio-verbal WM Forward and Ordering, and Visuospatial WM Forward and Backward), and Planning (La Portada de Antofagasta and FISA Maps). These results are consistent with previous empirical evidence and support the notion of a developmental relationship between EF performance and age. Additionally, this study contributes to understanding EF development in culturally specific contexts, highlighting the importance of contextually relevant assessment tools in evaluating cognitive development.
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OBJECTIVE: To determine whether it is the magnitude of early postnatal catch-up growth (CUG) in response to fetal growth restriction (FGR) or the FGR itself that negatively impacts cognitive outcome in a model of monochorionic twins discordant for fetal growth. STUDY DESIGN: This analysis is part of the LEMON study, a cohort study including all monochorionic twins with selective FGR aged 3 through 17 years. Growth measurements as documented by our primary care system were collected retrospectively. An age-appropriate neurodevelopmental test was performed generating a full-scale IQ (FSIQ). CUG at 2 years was calculated as (weight [kg] at 2 years-birth weight [kg]). We used a multivariable regression model investigating the association between FSIQ (outcome) and birth weight zscore, gestational age at birth and CUG at 2 years (predictors). Generalized estimating equations accounted for the fact that observations between cotwins are not independent. RESULTS: Median age at follow-up of the 46 included twin pairs was 11 (IQR 8-13) years. Birth weight z score and gestational age at birth were significantly associated with FSIQ, with ß-coefficients of 5.897 (95% CI 3.382-8.411), and 2.589 (95% CI 1.227-3.951), respectively (P < .0001). Adjusted for birth weight z score and gestational age, CUG in the first 2 years after birth was not significantly associated with FSIQ (ß-coefficient 0.108 [95% CI -1.373 to 1.590], P = .886). CONCLUSIONS: Our results, combining detailed growth measurements and neurodevelopmental follow-up in a discordant identical twin model, demonstrate that FGR itself rather than early postnatal CUG has negative consequences for cognitive development.
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3-Hydroxy-3-methylglutaric acidemia (HMGA) is a neurometabolic inherited disorder characterized by the predominant accumulation of 3-hydroxy-3-methylglutaric acid (HMG) in the brain and biological fluids of patients. Symptoms often appear in the first year of life and include mainly neurological manifestations. The neuropathophysiology is not fully elucidated, so we investigated the effects of intracerebroventricular administration of HMG on redox and bioenergetic homeostasis in the cerebral cortex and striatum of neonatal rats. Neurodevelopment parameters were also evaluated. HMG decreased the activity of glutathione reductase (GR) and increased catalase (CAT) in the cerebral cortex. In the striatum, HMG reduced the activities of superoxide dismutase, glutathione peroxidase, CAT, GR, glutathione S-transferase, and glucose-6-phosphate dehydrogenase. Regarding bioenergetics, HMG decreased the activities of succinate dehydrogenase and respiratory chain complexes II-III and IV in the cortex. HMG also decreased the activities of citrate synthase and succinate dehydrogenase, as well as complex IV in the striatum. HMG further increased DRP1 levels in the cortex, indicating mitochondrial fission. Finally, we found that the HMG-injected animals showed impaired performance in all sensorimotor tests examined. Our findings provide evidence that HMG causes oxidative stress, bioenergetic dysfunction, and neurodevelopmental changes in neonatal rats, which may explain the neuropathophysiology of HMGA.
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OBJECTIVE: This study aims to investigate the neuroprotective effects of cannabidiol (CBD) on neurodevelopmental impairments in rats subjected to neonatal hypoxia, specifically examining its potential to mitigate motor and sensory deficits without the confounding effects of ischemia. METHODS: Neonatal Sprague-Dawley rats were allocated to one of four groups: Control, Control-CBD, Hypoxia, and Hypoxia-CBD. Hypoxia was induced on postnatal days 0 and 1. CBD (50 mg/kg) was administered orally for 14 days starting at postnatal day 0. Neurodevelopmental outcomes were assessed using the Neurodevelopmental Reflex Testing in Neonatal Rat Pups scale and the Revised Neurobehavioral Severity Scale for rodents. Statistical analyses were conducted using two-way and one-way ANOVA, with Tukey's post-hoc tests for group comparisons. RESULTS: Pup weights were recorded on specified postnatal days, with no significant differences observed across the groups (p = 0.1834). Significant neurological impairments due to hypoxia were noted in the Control group compared to the Hypoxia group, particularly in hindlimb grasping on postnatal day 3 (p = 0.0025), posture on postnatal day 12 (p = 0.0073), and in general balance and sound reflex on postnatal day 20 (p = 0.0016 and p = 0.0068, respectively). Additionally, a statistically significant improvement in posture was observed in the Hypoxia-CBD group compared to the Hypoxia group alone (p = 0.0024). CONCLUSION: Our findings indicate that CBD possesses neuroprotective properties that significantly counteract the neurodevelopmental impairments induced by neonatal hypoxia in rats. This study not only supports the therapeutic potential of CBD in managing conditions characterized by neurodevelopmental challenges due to hypoxia but also underscores the necessity for further investigation into the specific molecular mechanisms driving CBD's neuroprotective effects. Further research is essential to explore CBD's clinical applications and its potential role in treating human neurodevelopmental disorders.
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Animais Recém-Nascidos , Canabidiol , Fármacos Neuroprotetores , Ratos Sprague-Dawley , Animais , Canabidiol/farmacologia , Fármacos Neuroprotetores/farmacologia , Ratos , Hipóxia/tratamento farmacológico , Hipóxia/complicações , Masculino , Feminino , Transtornos do Neurodesenvolvimento/prevenção & controle , Transtornos do Neurodesenvolvimento/tratamento farmacológico , Transtornos do Neurodesenvolvimento/etiologia , Modelos Animais de DoençasRESUMO
Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that impairs communication, socialization, and behavior. The association of ASD with folic acid has been investigated due to the importance of this vitamin for neurological health. This study is an update of the publication 'Folic acid and autism: What do we know?' and aims to systematically review studies examining the relationship between folic acid and ASD. The search resulted in 2,389 studies on folic acid and ASD, which were selected by two reviewers based on their titles and abstracts. Studies meeting the inclusion criteria were fully read. The 52 included studies involved 10,429 individuals diagnosed with ASD and assessed the intake of vitamin B6, folic acid, and vitamin B12; serum levels of these vitamins, homocysteine, and methionine; therapeutic interventions using folic acid; and the association between maternal exposure to this vitamin and the risk of ASD. The evidence of insufficient folic acid intake in most individuals with ASD remains consistent in this update. No association was found between maternal exposure to folic acid and the risk of ASD in their children. Despite observed improvements in communication, socialization, and behavior in individuals with ASD following folic acid interventions, it is crucial to consider the individuality and complexity of ASD. Given the relevance of the topic, there remains a need for more high-quality research and clinical trials characterized by rigorous methodological designs.
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AIM: Congenital Zika Virus Syndrome (CZS) presents notable hurdles to neurodevelopment, with language development emerging as a crucial aspect. This study investigates sleep patterns and language skills in children with CZS, aiming to explore the potential synchronization of sleep development with their neurodevelopment. METHOD: We studied cross-sectionally 135 children with CZS aged 0 to 48 months, investigating sleep using the BISQ Questionnaire. Language development was assessed using the Early Language Milestone Scale, while motor development and cognitive and social ability were assessed using the Bayley Scales of Infant and Young Child Development 3rd edition. We also studied longitudinally a cohort of 16 children (initially aged 0 to 12 months) whom we followed for four years, assessing at one-year intervals. RESULTS: Sleep disturbances and language deficits were highly frequent in this population. In the 0-12 months group, a late bedtime and frequent nighttime awakenings were associated with poorer auditory expressive skills. At 13-24 months, nighttime awakenings were associated with poorer auditory expressive skills, while among 25-36-month-olds decreased auditory receptive skills were associated with longer sleep onset latency and reduced nighttime sleep duration. CONCLUSION: The brain alterations caused by Zika virus infection affect both sleep disturbances and delays in language development. It is possible that sleep disturbance may be a mediating factor in the pathway between CZS and delayed language development, as the three analyzed language skills showed a correlation with sleep parameters.
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Desenvolvimento da Linguagem , Sono , Infecção por Zika virus , Humanos , Infecção por Zika virus/complicações , Infecção por Zika virus/fisiopatologia , Infecção por Zika virus/virologia , Infecção por Zika virus/congênito , Lactente , Feminino , Masculino , Pré-Escolar , Sono/fisiologia , Recém-Nascido , Estudos Transversais , Transtornos do Sono-Vigília/fisiopatologia , Transtornos do Sono-Vigília/virologia , Zika virus/fisiologia , Estudos Longitudinais , Inquéritos e Questionários , Transtornos do Desenvolvimento da Linguagem/fisiopatologia , Transtornos do Desenvolvimento da Linguagem/virologiaRESUMO
The S100B is a member of the S100 family of "E" helix-loop- "F" helix structure (EF) hand calcium-binding proteins expressed in diverse glial, selected neuronal, and various peripheral cells, exerting differential effects. In particular, this review compiles descriptions of the detection of S100B in different brain cells localized in specific regions during the development of humans, mice, and rats. Then, it summarizes S100B's actions on the differentiation, growth, and maturation of glial and neuronal cells in humans and rodents. Particular emphasis is placed on S100B regulation of the differentiation and maturation of astrocytes, oligodendrocytes (OL), and the stimulation of dendritic development in serotoninergic and cerebellar neurons during embryogenesis. We also summarized reports that associate morphological alterations (impaired neurite outgrowth, neuronal migration, altered radial glial cell morphology) of specific neural cell groups during neurodevelopment and functional disturbances (slower rate of weight gain, impaired spatial learning) with changes in the expression of S100B caused by different conditions and stimuli as exposure to stress, ethanol, cocaine and congenital conditions such as Down's Syndrome. Taken together, this evidence highlights the impact of the expression and early actions of S100B in astrocytes, OL, and neurons during brain development, which is reflected in the alterations in differentiation, growth, and maturation of these cells. This allows the integration of a spatiotemporal panorama of S100B actions in glial and neuronal cells in the developing brain.
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Methylphenidate (MPH) is a central nervous system stimulant drug and a first order prescription in the treatment of Attention Deficit Hyperactivity Disorder (ADHD). Although MPH biochemistry in neurodevelopment is not completely understood, studies showed it alters energy metabolism in rat brains. ADHD prevalence during neurodevelopment is related to males and the investigation has been mainly done in these subjects, therefore, little is known about MPH action in females and, consequently, about sexual dimorphism. In the present study we evaluated markers of mitochondrial dynamics (DRP1 and MFN2, fission and fusion, respectively), biogenesis (mtTFA) and bioenergetics (respiratory chain complexes) in prefrontal cortex of male and female juvenile rats submitted to exposure to MPH to better understand MPH effect during postnatal neurodevelopment. ATP and oxidative stress levels were also evaluated. Wistar rats received intraperitoneal injection of MPH (2.0 mg/kg) or control (saline), once a day, from 15th to 45th day of age. Results showed that MPH increased DRP1 and decreased MFN2, as well as increased mtTFA in prefrontal cortex of male rats. In female, MPH decreased NRF1 and increased Parkin, which are mitochondrial regulatory proteins. Respiratory chain complexes (complex I, SDH, complexes III and IV), ATP production and oxidative stress parameters were altered and shown to be sex-dependent. Taken together, results suggest that chronic MPH exposure at an early age in healthy animals changes mitochondrial dynamics, biogenesis and bioenergetics differently depending on the sex of the subjects.
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Estimulantes do Sistema Nervoso Central , Dinaminas , Metabolismo Energético , Metilfenidato , Dinâmica Mitocondrial , Estresse Oxidativo , Córtex Pré-Frontal , Ratos Wistar , Animais , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Metilfenidato/farmacologia , Masculino , Dinâmica Mitocondrial/efeitos dos fármacos , Feminino , Estimulantes do Sistema Nervoso Central/farmacologia , Metabolismo Energético/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Dinaminas/metabolismo , Ratos , Caracteres Sexuais , Trifosfato de Adenosina/metabolismo , GTP Fosfo-Hidrolases/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Proteínas Mitocondriais , Ubiquitina-Proteína LigasesRESUMO
The brain exhibits remarkable neuronal diversity which is critical for its functional integrity. From the sheer number of cell types emerging from extensive transcriptional, morphological, and connectome datasets, the question arises of how the brain is capable of generating so many unique identities. 'Terminal selectors' are transcription factors hypothesized to determine the final identity characteristics in post-mitotic cells. Which transcription factors function as terminal selectors and the level of control they exert over different terminal characteristics are not well defined. Here, we establish a novel role for the transcription factor broad as a terminal selector in Drosophila melanogaster. We capitalize on existing large sequencing and connectomics datasets and employ a comprehensive characterization of terminal characteristics including Perturb-seq and whole-cell electrophysiology. We find a single isoform broad-z4 serves as the switch between the identity of two visual projection neurons LPLC1 and LPLC2. Broad-z4 is natively expressed in LPLC1, and is capable of transforming the transcriptome, morphology, and functional connectivity of LPLC2 cells into LPLC1 cells when perturbed. Our comprehensive work establishes a single isoform as the smallest unit underlying an identity switch, which may serve as a conserved strategy replicated across developmental programs.
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Consumption of sucrose-sweetened drinks (SSDs) during pregnancy and breastfeeding can lead to various health and metabolism issues, but the potential impact on neurodevelopment and long-term effects remains unclear. This study aims to examine how maternal consumption of SSDs during gestation and lactation influences anxiety and depression-related behavior in adult offspring. Adult female CD-1 mice were randomly assigned to a control group (CG) or a sucrose group (SG) 2 weeks before gestation. The SG had 2 h of access to an SSD (15% w/w, 0.6 kcal/ml) for 2 weeks before mating, during pregnancy, and throughout lactation, totaling 8 weeks. Adult offspring were then evaluated for depressive-related behaviors and anxiety-related behaviors. Our findings reveal that perigestational consumption of SSDs does not lead to offspring presenting behaviors related to depression, but it does increase swimming behavior. However, maternal consumption of SSDs could impact the fighting response due to a diminished motivational component. In contrast, perigestational consumption of SSDs has apparent effects on anxiety-related behavior. Furthermore, female offspring appeared to be particularly vulnerable, exhibiting a higher anxiety index compared with controls. These findings indicate that females could be more vulnerable to the effects of maternal consumption of SSDs, being more susceptible to the presence of anxiety-related behaviors.