Maternal exposure to glyphosate increased the risk of adverse neurodevelopmental outcomes in rodent offspring: A systematic review.

The potential neurotoxicity of environmental contaminants, such as pesticides, is implicated in the etiology of neurodevelopmental disorders, particularly given the heightened vulnerability of the developing brain. Among these contaminants, glyphosate, a widely used herbicide, has been linked to alterations in neurodevelopment, though its precise neurotoxic mechanisms are not fully elucidated. In this context, our systematic review evaluates the impact of maternal exposure to glyphosate alone (GLY) or glyphosate-based-herbicide (GBH) on neurodevelopmental and behavioral outcomes in rodent offspring. This assessment encompasses a comprehensive examination of behavioral, biochemical, morphological, and genetic alterations resulting from perinatal glyphosate exposure. The Systematic review protocol was registered in the platform Open Science Framework (OSF) following the guidelines of the Systematic Review Center for Laboratory Animal Experimentation (SYRCLE). Our analysis demonstrate that glyphosate disrupts redox signaling, metabolic pathways, and neurotransmitter systems, thereby affecting brain architecture and function across genders and developmental stages in rodents. The results of this review elucidate the extensive neurochemical and behavioral disruptions attributed to glyphosate, highlighting the critical need for advanced neurodevelopmental risk assessment methodologies. Such refined evaluations are vital to inform targeted prevention and intervention strategies in the context of environmental neurotoxicants.

Prenatal polycyclic aromatic hydrocarbon exposure and neurodevelopment among children in Puerto Rico.

Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental contaminants produced through the combustion of organic matter, with sources ranging from traffic pollution to diet. Although PAH exposure has been associated with adverse health effects, few studies have examined its impact on neurodevelopmental delay (NDD). Thus, our study aims to investigate the effect of prenatal PAH exposure on the odds of NDD. We measured 7 hydroxylated PAH metabolites in spot urine samples collected up to three times during pregnancy in the PROTECT birth cohort. NDD was identified using score cutoffs from the Ages and Stages Questionnaire, 3rd edition offered in Spanish, across five domains at 12, 24, 36, and 48 months. We utilized logistic regression and mixed effects logistic regression models to assess associations between prenatal PAH concentrations and NDD. Our results showed mostly lower odds of NDD with higher PAH exposure (p < 0.05). However, male children showed higher odds of NDD in relation to PAH exposure, particularly in the Fine Motor domain. For example, 1-hydroxypyrene was associated with 1.11 (1.01, 1.23) times odds of delay in fine motor function in male children versus 0.91 (0.82, 1.00) times odds in female children. Our preliminary sex-specific results suggest that PAH exposure may impact neurodevelopment in male children and prompt further investigation into the potential sex-specific mechanisms of PAHs on motor function.

Pre-natal and early life lead exposure and childhood inhibitory control: an item response theory approach to improve measurement precision of inhibitory control.

BACKGROUND: Neurodevelopmental performance tasks are often separately analyzed, even when they tap into a similar construct. This may yield mixed findings for associations of an exposure-neurobehavioral outcome. We develop an item response theory (IRT) approach to integrate multiple task variables together to improve measurement precision of the underlying construct. We apply this approach to create an integrative measure of childhood inhibitory control, and study impacts of pre/post-natal lead exposure. METHODS: Using data from a prospective cohort based in Mexico (N = 533), we created an inhibitory control scale that integrates accuracy and reaction time information from four inhibitory control tasks (Go/NoGo Letter, Go/NoGo Neutral, Go/NoGo Happy, Delis-Kaplan Executive Function System (D-KEFS) Color-Word Interference Test, Condition 3). Using a generalized partial credit item response theory model, we estimated an inhibitory control index for each participant. We then assessed adjusted associations between umbilical cord blood and 4-year lead and childhood inhibitory control. We developed a resampling approach to incorporate error estimates from the inhibitory control variable to confirm the consistency of the lead-inhibitory control associations. We modeled time-varying associations of lead with each inhibitory control measure separately. RESULTS: Participants had a median age of 9 years; 51.4% were males. Umbilical cord blood [-0.06 (95% CI: -0.11, -0.01)] and 4-year lead [-0.07 (95% CI: -0.12, -0.02)] were associated with inhibitory control index at 8-10 years. A resampling approach confirmed that 4-year lead was consistently associated with childhood inhibitory control index. Umbilical cord blood and 4-year lead were each associated with 3 out of 8 measures in separate models. CONCLUSION: This is the first application of IRT in environmental epidemiology to create a latent variable for inhibitory control that integrates accuracy and reaction time information from multiple, related tasks. This framework can be applied to other correlated neurobehavioral assessments or other phenotype data.

The Influence of Nutritional Status on Brain Development: Benefits of Exclusive Breastfeeding.

BACKGROUND: This study aimed to conduct a narrative review approaching the effects of exclusive breastfeeding on neuropsychomotor development. The goal was to provide evidence-based knowledge to inform healthcare practices and policies and promote optimized infant feeding strategies. METHODS: Our study reviewed the relevant literature from May and June 2024, covering the publication period between 2013 and 2024. The PubMed database was utilized and searched for articles using keywords such as "Brain", "Growth", "Development", and "Breastfeeding", employing Boolean operators such as "AND", "OR", and "NOT." RESULTS: Our search initially screened 15,412 studies, resulting in 600 articles. Eleven studies met our inclusion criteria and provided relevant information on the topic. Several studies have shown that exclusive breastfeeding and its duration are beneficial for neural development. Research suggests that breastfeeding improves brain architecture, white matter development, and cognitive performance. Additionally, studies indicate that the mother's intake of omega-3 fatty acids can enhance infant brain development, and specific micronutrients in breast milk, such as myo-inositol, may contribute to neural connectivity. Some findings also suggest that the child's sex may play a role in how breast milk benefits the brain. Furthermore, there is evidence of the strong influence of epigenetic compounds on the neurodevelopmental benefits of exclusive breastfeeding. CONCLUSIONS: This narrative review revealed findings that indicate breast milk has a positive impact on brain development. This emphasizes that breast milk has a positive impact on brain development. It underscores the importance of conducting additional research to understand how breastfeeding specifically influences neurodevelopment.

[Guide to neurological follow-up in premature newborns]. / Guía de seguimiento neurológico en recién nacidos prematuros.

One in ten babies are born preterm, as defined as being less than 37 weeks of gestational age. Premature births are associated with a high risk of poor neurodevelopmental outcomes, including hearing, visual, motor, and cognitive impairments. Currently, there is no specific standardization for neurological follow-up infants born premature. Most formal neonatal intensive care units, follow-up programs monitor children until early childhood. However, some deficits, such as mild cognitive impairment, may only become apparent in school years. This review outlines a neurological follow-up timeline, as well as the different standardized measures that can be used to monitor development to ensure that children born preterm receive timely and appropriate therapies and services.

Uno de cada diez bebés nacidos es prematuro, el cual se define como el nacido antes de las 37 semanas de edad gestacional. La prematuridad está asociada con un alto riesgo de trastornos del neurodesarrollo con limitaciones en la audición, visión, área cognitiva y motora. Actualmente, no existen programas estandarizados específicos para el seguimiento neurológico de los prematuros. La mayoría son desarrollados por las unidades de cuidados intensivos neonatales y dan seguimiento hasta la edad pre-escolar. Sin embargo, algunas deficiencias, como el deterioro cognitivo leve, son reconocidos tardíamente. Esta revisión describe un cronograma para el seguimiento neurológico y las herramientas estandarizadas que pueden utilizarse para vigilar el desarrollo y asegurar que los niños nacidos prematuros reciban terapias y otros servicios adecuados y oportunos.

[Autism: associated medical conditions]. / Autismo: condiciones médicas asociadas.

Autism will accompany people throughout life with variations in its evolution and is frequently associated with other neurodevelopmental disorders (intellectual disability, attention deficit hyperactivity disorder, motor clumsiness, language disorder), neuropsychiatric disorders (depression, anxiety, schizophrenia, catatonia), epilepsy, sleep disorders, gastrointestinal disorders. In addition to the disorders typical of autism, we must consider an entire range of conditions, since their identification and adequate treatment will allow a better quality-of-life for people with autism. In 35% of cases, we can identify neurogenetic conditions which will allow us to prevent or identify associated medical entities. In this work we will analyze two groups, in a purely organizational way, medical conditions associated with defined entities (Down, Angelman, Fragile X, Rett, Phelan-McDermid and Timothy syndromes) and those that can be consistently associated in people with autism without an identified entity.

El autismo acompañará a las personas a lo largo de toda la vida, con variaciones en su evolución, está frecuentemente asociado a otros trastornos del neurodesarrollo (discapacidad intelectual, trastorno de déficit de atención e hiperactividad, torpeza motriz, trastorno del lenguaje), trastornos neuropsiquiátricos (depresión, ansiedad, esquizofrenia, catatonía), epilepsia, trastornos de sueño, trastornos gastrointestinales. Además de los trastornos propios del autismo, debemos tener en cuenta todo este abanico de condiciones, ya que su identificación y tratamiento permitirán una mejor calidad de vida. En el 35% de los casos podemos identificar entidades neurogenéticas, lo cual permitirá prevenir o identificar más rápidamente condiciones médicas asociadas. En este trabajo analizaremos dos grupos, de forma puramente organizativa, las condiciones médicas asociadas a entidades definidas (síndromes de Down, Angelman, X frágil, Rett, Phelan-McDermid y Timothy) y las que pueden asociarse consistentemente en personas con autismo sin una entidad identificada.

[The impact of congenital heart disease on neurodevelopment]. / El impacto de las cardiopatías congénitas en el neurodesarrollo.

It is estimated that about 1 in 100 live births has a congenital heart disease (CHD). Cognitive deficit, academic difficulties, and behavioral abnormalities, in combination, represent the most common morbidity affecting quality of life in survivors with CHD. Developmental dysfunction results from a complex interaction between patient-specific factors such as genetic susceptibility, cardiac diagnosis, fetal development, and environmental factors such as preoperative events, supportive techniques during surgical repair, postoperative events, socioeconomic status. A comprehensive neurodevelopmental assessment in all children with CHD is critical to identify any need for intervention early and provide the support needed to optimize their long-term development.

Se estima que aproximadamente 1 de cada 100 nacidos vivos presenta una cardiopatía congénita (CC). El déficit cognitivo, las dificultades académicas y anomalías conductuales, en combinación, representan la morbilidad más común que afecta la calidad de vida en sobrevivientes con CC. La disfunción del desarrollo resulta de una interacción compleja entre factores específicos del paciente como susceptibilidad genética, tipo de cardiopatía, desarrollo fetal y factores ambientales tales como eventos preoperatorios, técnicas de apoyo durante la reparación quirúrgica, eventos posoperatorios, estatus socioeconómico. Una evaluación integral del neurodesarrollo en todos los niños con CC es fundamental para identificar tempranamente cualquier necesidad de intervención y proporcionar el apoyo necesario para optimizar su desarrollo a largo plazo.

Differential Impact of Adolescent or Adult Stress on Behavior and Cortical Parvalbumin Interneurons and Perineuronal Nets in Male and Female Mice.

BACKGROUND: Stress has become a common public health concern, contributing to the rising prevalence of psychiatric disorders. Understanding the impact of stress considering critical variables, such as age, sex, and individual differences, is of the utmost importance for developing effective intervention strategies. METHODS: Stress effects (daily footshocks for 10 days) during adolescence (postnatal day [PND] 31-40) and adulthood (PND 65-74) were investigated on behavioral outcomes and parvalbumin (PV)-expressing GABAergic interneurons and their associated perineuronal nets (PNNs) in the prefrontal cortex of male and female mice 5 weeks post stress. RESULTS: In adulthood, adolescent stress induced behavioral alterations in male mice, including anxiety-like behaviors, social deficits, cognitive impairments, and altered dopamine system responsivity. Applying integrated behavioral z-score analysis, we identified sex-specific differences in response to adolescent stress, with males displaying greater vulnerability than females. Furthermore, adolescent-stressed male mice showed decreased PV+ and PNN+ cell numbers and PV+/PNN+ colocalization, while in females, adolescent stress reduced prefrontal PV+/PNN+ colocalization in the prefrontal cortex. Further analysis identified distinct behavioral clusters, with certain females demonstrating resilience to adolescent stress-induced deficits in sociability and PV+ cell number. Adult stress in male and female mice did not cause long-lasting changes in behavior and PV+ and PNN+ cell number. CONCLUSION: Our findings indicate that the timing of stress, sex, and individual variabilities seem to be determinants for the development of behavioral changes associated with psychiatric disorders, particularly in male mice during adolescence.

Executive functions and their relationship with age: Insights from a novel neuropsychological Assessment Battery in Children-a pilot study.

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.

Does Catch-Up Growth Come with a Cognitive Cost? Cognitive Outcome and Growth Patterns in Growth Discordant Identical Twins.

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.

Maternal immune response during pregnancy and neurodevelopmental outcomes: A longitudinal approach.

Background and objectives: The neurodevelopment of the offspring is suggested to be influenced by the maternal immune system's responses throughout pregnancy, which in turn is also vulnerable to maternal psychosocial stress conditions. Therefore, our main goal was to investigate whether maternal peripheral immunological biomarkers (IB) during two stages of gestation are associated with distinct neurodevelopmental trajectories in the first two years of life. As a second goal, we also explored the association between maternal distal (childhood) and proximal (gestation) stressful experiences and the immunological markers assessed during pregnancy. Methods: Maternal childhood trauma, depressive and anxiety symptoms, and peripheral IB (IFNγ, IL-10, IL1ß, IL6, IL8, TNFα, EGF, IL13, IL17, IL1Ra and IL4) were measured at baseline (8-16 weeks of pregnancy) and at 30 weeks of pregnancy in 160 women. The participants had the blood samples collected from two randomized clinical trials conducted by the same team and methods in the same community. A Principal Component Analysis (PCA) was implemented to create meaningful composite variables that describe the cytokines joint variation. Finally, linear mixed-effects modeling was used to investigate the influence of inflammatory biomarkers, maternal childhood trauma, anxiety, and depressive symptoms on Bayley's III scores trajectories. Results: The IB profile during the 3rd trimester of pregnancy predicted the offspring's neurodevelopmental trajectories in the first two years of life. The components derived from PCA were important predictors and captured different immune responses, reflecting both pro- and anti-inflammatory states. Maternal stressful experiences did not correlate with the immunological markers. Although not a reliable predictor alone, maternal psychosocial stress at the 1st trimester of pregnancy interacted with the mother's immune response while predicting the neurodevelopmental scores during the first two years of life. Conclusions: Our results underscore the importance of the maternal immune response during pregnancy in shaping the neurodevelopmental trajectory of the offspring. Additionally, we observed that the maternal distress at the early stages of pregnancy has an incremental effect on the neurodevelopmental outcome but depends upon the immune response.

Effect of cannabidiol as a neuroprotective agent on neurodevelopmental impairment in rats with neonatal hypoxia.

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.

S100B actions on glial and neuronal cells in the developing brain: an overview.

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.

Association between Sleep and Language Development in Children with Congenital Zika Syndrome.

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.

3-Hydroxy-3-Methylglutaric Acid Disrupts Brain Bioenergetics, Redox Homeostasis, and Mitochondrial Dynamics and Affects Neurodevelopment in Neonatal Wistar Rats.

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.

Folic acid and autism: updated evidences.

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.

Effects of methylphenidate on mitochondrial dynamics and bioenergetics in the prefrontal cortex of juvenile rats are sex-dependent.

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.

Transición de jóvenes con trastornos del neurodesarrollo / The transition of youth with neurodevelopmental disorders

La transición de la atención pediátrica a la de adultos, en adolescentes y jóvenes con condiciones crónicas de salud, es un proceso necesario y difícil. El proceso de transición de estos pacientes contará con diferentes matices según la condición de salud, las características del sistema sanitario, los equipos de salud involucrados y los factores contextuales del joven y su familia. El objetivo central es que a través de una autonomía progresiva el joven llegue a ser un adulto competente en cuanto a asumir y manejar sus necesidades de salud, relaciones sociales y laborales que su enfermedad crónica le permita. Pero estos objetivos se ven interferidos cuando hablamos de jóvenes con condiciones crónicas que involucran el neurodesarrollo y es más complejo aún cuando nos referimos a jóvenes que no serán autónomos. Para las familias y cuidadores de estos jóvenes los centros pediátricos son un entorno más protegido que cuesta dejar. Por todo esto es que, si bien hay lineamientos generales a tener en cuenta, cada equipo debe revisar sus resultados para poder avanzar. Aún no se logró consenso acerca de cuál es el momento óptimo, la edad y las mejores estrategias, aunque es reconocida la dificultad para implementar un programa adecuado y más aún evaluar los resultados de los programas que se utilizan en la transición; se llevan adelante programas "genéricos" utilizados para diferentes enfermedades crónicas, o específicos para una enfermedad, otros programas combinan ambas estrategias. Basados en lo anterior hay jóvenes y familias que requieren un armado "artesanal y a medida" (AU)

The transition from pediatric to adult care for adolescents and young people with chronic health conditions is a necessary yet challenging process. This transition will vary depending on the health condition, the characteristics of the health system, the health teams involved, and the contextual factors of the youth and their family. The central objective is for the youth to achieve progressive autonomy, becoming a competent adult capable of managing their health needs, social, and work relationships, as allowed by their chronic disease. However, these objectives become more complicated when dealing with young people with chronic conditions involving neurodevelopment, and even more so for those who will never achieve autonomy. For the families and caregivers of these youths, pediatric centers offer a more protected environment that is difficult to leave. For all these reasons, while general guidelines should be considered, each team must review its results to move forward. Consensus has not yet been reached on the optimal time, age, and best strategies for transition. It is recognized that implementing an adequate program is challenging, and evaluating the results of these programs is even more difficult. There are "generic" programs used for various chronic diseases, as well as disease-specific programs, and some programs combine both strategies. Given these complexities, some young people and their families require a "handcrafted and tailor-made" approach (AU)

Gestational hypothyroxinemia induces ASD-like phenotypes in behavior, proinflammatory markers, and glutamatergic protein expression in mouse offspring of both sexes.

Background: The prevalence of autism spectrum disorder (ASD) has significantly risen in the past three decades, prompting researchers to explore the potential contributions of environmental factors during pregnancy to ASD development. One such factor of interest is gestational hypothyroxinemia (HTX), a frequent condition in pregnancy associated with cognitive impairments in the offspring. While retrospective human studies have linked gestational HTX to autistic traits, the cellular and molecular mechanisms underlying the development of ASD-like phenotypes remain poorly understood. This study used a mouse model of gestational HTX to evaluate ASD-like phenotypes in the offspring. Methods: To induce gestational HTX, pregnant mice were treated with 2-mercapto-1-methylimidazole (MMI), a thyroid hormones synthesis inhibitor, in the tap-drinking water from embryonic days (E) 10 to E14. A separate group received MMI along with a daily subcutaneous injection of T4, while the control group received regular tap water during the entire pregnancy. Female and male offspring underwent assessments for repetitive, anxious, and social behaviors from postnatal day (P) 55 to P64. On P65, mice were euthanized for the evaluation of ASD-related inflammatory markers in blood, spleen, and specific brain regions. Additionally, the expression of glutamatergic proteins (NLGN3 and HOMER1) was analyzed in the prefrontal cortex and hippocampus. Results: The HTX-offspring exhibited anxious-like behavior, a subordinate state, and impaired social interactions. Subsequently, both female and male HTX-offspring displayed elevated proinflammatory cytokines in blood, including IL-1ß, IL-6, IL-17A, and TNF-α, while only males showed reduced levels of IL-10. The spleen of HTX-offspring of both sexes showed increased Th17/Treg ratio and M1-like macrophages. In the prefrontal cortex and hippocampus of male HTX-offspring, elevated levels of IL-17A and reduced IL-10 were observed, accompanied by increased expression of hippocampal NLGN3 and HOMER1. All these observations were compared to those observed in the Control-offspring. Notably, the supplementation with T4 during the MMI treatment prevents the development of the observed phenotypes. Correlation analysis revealed an association between maternal T4 levels and specific ASD-like outcomes. Discussion: This study validates human observations, demonstrating for the first time that gestational HTX induces ASD-like phenotypes in the offspring, highlighting the need of monitoring thyroid function during pregnancy.