Disruption Of Brain Development Research Articles

Anesthetic neurotoxicity in the developing brain: an update on theinsights and implications for fetal surgery.

This review describes an in-depth analysis of the neurotoxicity associated with the anesthetic agents used during fetal surgery, intending to highlight the importance of understanding the effects of general anesthetics on the developing brain, particularly in the context of open fetal surgery, where high doses are applied to facilitate surgical access and augment uterine relaxation. We examined evidence from preclinical studies in rodents and primates, along with studies in human subjects, with the results collectively suggesting that general anesthetics can disrupt brain development and lead to long-lasting neurological deficits. Our review underscores the clinical implications of these findings, indicating an association between extensive anesthetic exposure in early life and subsequent cognitive deficits. The current standard of anesthetic care for fetal surgical procedures was scrutinized, and recommendations have been proposed to mitigate the risk of anesthetic neurotoxicity. These recommendations emphasize the need for careful selection of anesthetic techniques to minimize fetal exposure to potentially harmful agents. In conclusion, while the benefits of fetal surgery in addressing immediate risks often outweigh the potential neurotoxic effects of anesthesia, the long-term developmental impacts nevertheless warrant consideration. Our analysis suggests that the use of general anesthetics in fetal surgery, especially at high doses, poses a significant risk of developmental neurotoxicity. As such, it is imperative to explore safer alternatives, such as employing different methods of uterine relaxation and minimizing the use of general anesthetics, to achieve the necessary surgical conditions. Further research, particularly in clinical settings, is essential to fully understand the risks and benefits of anesthetic techniques in fetal surgery.

Basic helix-loop-helix transcription factor BHLHE22 monoallelic and biallelic variants cause a neurodevelopmental disorder with agenesis of the corpus callosum, intellectual disability, tone and movement abnormalities.

BHLHE22 encodes a Class II basic helix-loop-helix transcription factor (bHLH). It is expressed exclusively in the retina and central nervous system (CNS), and functions as an important regulator of retinogenesis and neuronal differentiation. Mice lacking bhlhe22 show nearly complete loss of three brain comminsure, including the corpus callosum. Here we report eleven individuals from nine unrelated families with BHLHE22 variants, with a neurodevelopmental disorder presenting with absent or limited speech, severely impaired motor abilities, intellectual disability (ID), involuntary movements, autistic traits with stereotypies, abnormal muscle tone. The majority of individuals have partial or complete agenesis of the corpus callosum (ACC). Additional symptoms comprised epilepsy, variable dysmorphic features, and eye anomalies. One additional individual had spastic paraplegia without delayed development and ACC, expanding the phenotype to milder and later onset forms. Four individuals carry de novo missense variants within the highly conserved helix-loop-helix domain while seven individuals from five unrelated families carry a recurrent homozygous frameshift variant, p.(Gly74Alafs*18). Our findings implicate BHLHE22 variants in causing a previously unidentified autosomal dominant and recessive neurodevelopmental disorder associated with ACC, severe motor, language, and cognitive delays, abnormal tone, and involuntary movements. To our knowledge, this is the first report of Class II bHLH variants in humans shown to significantly disrupt brain development, cognition, and movement.

Mutant huntingtin impairs neurodevelopment in human brain organoids through CHCHD2-mediated neurometabolic failure

Expansion of the glutamine tract (poly-Q) in the protein huntingtin (HTT) causes the neurodegenerative disorder Huntington’s disease (HD). Emerging evidence suggests that mutant HTT (mHTT) disrupts brain development. To gain mechanistic insights into the neurodevelopmental impact of human mHTT, we engineered male induced pluripotent stem cells to introduce a biallelic or monoallelic mutant 70Q expansion or to remove the poly-Q tract of HTT. The introduction of a 70Q mutation caused aberrant development of cerebral organoids with loss of neural progenitor organization. The early neurodevelopmental signature of mHTT highlighted the dysregulation of the protein coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2), a transcription factor involved in mitochondrial integrated stress response. CHCHD2 repression was associated with abnormal mitochondrial morpho-dynamics that was reverted upon overexpression of CHCHD2. Removing the poly-Q tract from HTT normalized CHCHD2 levels and corrected key mitochondrial defects. Hence, mHTT-mediated disruption of human neurodevelopment is paralleled by aberrant neurometabolic programming mediated by dysregulation of CHCHD2, which could then serve as an early interventional target for HD.

Zika virus vertical transmission induces neuroinflammation and synapse impairment in brain cells derived from children born with Congenital Zika Syndrome

Zika virus (ZIKV) infection was first reported in 2015 in Brazil as causing microcephaly and other developmental abnormalities in newborns, leading to the identification of Congenital Zika Syndrome (CZS). Viral infections have been considered an environmental risk factor for neurodevelopmental disorders outcome, such as Autism Spectrum Disorder (ASD). Moreover, not only the infection per se, but maternal immune system activation during pregnancy, has been linked to fetal neurodevelopmental disorders. To understand the impact of ZIKV vertical infection on brain development, we derived induced pluripotent stem cells (iPSC) from Brazilian children born with CZS, some of the patients also being diagnosed with ASD. Comparing iPSC-derived neurons from CZS with a control group, we found lower levels of pre- and postsynaptic proteins and reduced functional synapses by puncta co-localization. Furthermore, neurons and astrocytes derived from the CZS group showed decreased glutamate levels. Additionally, the CZS group exhibited elevated levels of cytokine production, one of which being IL-6, already associated with the ASD phenotype. These preliminary findings suggest that ZIKV vertical infection may cause long-lasting disruptions in brain development during fetal stages, even in the absence of the virus after birth. These disruptions could contribute to neurodevelopmental disorders manifestations such as ASD. Our study contributes with novel knowledge of the CZS outcomes and paves the way for clinical validation and the development of potential interventions to mitigate the impact of ZIKV vertical infection on neurodevelopment.

The Effectiveness of Milk Supplementation on Weight and Height/Length in Stunted Toddles

Stunting or a short child was described as a toddler whose height was lower than the standard height for toddlers his age. Until now, the prevalence of stunted toddlers in Indonesia is still high. The prevalence of stunted toddlers at the Plaosan Community Health Center in the last 3 years showed an increase. The cause of stunting, apart from infection, is also related to nutritional deficiencies (micronutrients and macronutrients). The adverse effected of stunting in the short term are disruption of brain development, intelligenced, impaired physical growth, and metabolic disorders in the body. Supplementary feeded is one of the solutions in handling stunting. This study aims to determined the effectiveness of milk feeded on the weight and height/length of stunted toddlers. The typed of research used was pre-experimental with a one group pretest posttest design. The sample used a total population of 56 toddlers. The dependent variable in this studied was the weight and height/length of stunted toddlers, the independent variabled is the provision of milk for toddlers. Data collection used weight and height measurement sheets and milk feeded observation sheets. Comparative data analysis was conducted using the paired samples t test statistical test. The results of the study show that the average body weight before giving milk was 8737.5 mm and after giving milk 8923.2 mm. Body height/length before milk feeding was 804.6 mm and after milk feeding was 806.63 mm. Different test using paired samples t test obtaining the conclusion that there is a significant difference in the increase in body weight of toddlers with a significance level of 0.000 (p <0.05) and there is a significant difference in increasing the height of toddlers with a significance level of 0.000 (p <0.05). Conclution: Milk is effective to increase the weight and height/length of toddlers, so it is advisable for mothers of toddlers to get their children used to a glass of milk everyday.

Penyuluhan Mengenai Pemberian MP-ASI Tinggi Protein Hewani Untuk Pencegahan Stunting

Stunting is a condition of failure to thrive in children under five (for babies under five years of age) which is caused by chronic malnutrition so that the child is too short for his age. Stunting causes children to not reach their maximum height and disrupts brain development which will affect cognitive abilities. One in five children in Indonesia is reported to be stunted. The long-term impact of stunting will cause children to have difficulty receiving lessons, decreased learning achievement, decreased work productivity, low income and minimal participation in community activities. The cause of stunting in toddlers is often the result of many factors related to poverty, including poor diet, health, hygiene and the environment. The current effort being made is to provide education about high protein foods. The education provided aims to enable mothers of toddlers to play a role in providing a healthy, high-protein menu so that it can prevent the incidence of stunting. This community service is carried out with the aim of increasing the knowledge and understanding of mothers of toddlers regarding providing MP-ASI high in animal protein to prevent stunting. It is hoped that after participating in this service activity, mothers of toddlers will be able to provide MP-ASI high in animal protein for toddlers to support their children's height growth.

Unraveling Multimodal Brain Signatures: Deciphering Transdiagnostic Dimensions of Psychopathology in Adolescents

Adolescent psychiatric disorders arise from intricate interactions of clinical histories and disruptions in brain development. While connections between psychopathology and brain functional connectivity are studied, the use of deep learning to elucidate overlapping neural mechanisms through multimodal brain images remains nascent. Utilizing two adolescent datasets—the Philadelphia Neurodevelopmental Cohort (PNC, n = 1100) and the Adolescent Brain Cognitive Development (ABCD, n = 7536)—this study employs interpretable neural networks and demonstrates that incorporating brain morphology, along with functional and structural networks, augments traditional clinical characteristics (age, gender, race, parental education, medical history, and trauma exposure). Predictive accuracy reaches 0.37–0.464 between real and predicted general psychopathology and four psychopathology dimensions (externalizing, psychosis, anxiety, and fear). The brain morphology and connectivities within the frontoparietal, default mode network, and visual associate networks are recurrent across general psychopathology and four psychopathology dimensions. Unique structural and functional pathways originating from the cerebellum, amygdala, and visual‐sensorimotor cortex are linked with these individual dimensions. Consistent findings across both PNC and ABCD affirm the generalizability. The results underscore the potential of diverse sensory inputs in steering executive processes tied to psychopathology dimensions in adolescents, hinting at neural avenues for targeted therapeutic interventions and preventive strategies.

Role of epigenetics and alterations in RNA metabolism in leukodystrophies.

Leukodystrophies are a class of rare heterogeneous disorders which affect the white matter of the brain, ultimately leading to a disruption in brain development and a damaging effect on cognitive, motor and social-communicative development. These disorders present a great clinical heterogeneity, along with a phenotypic overlap and this could be partially due to contributions from environmental stimuli. It is in this context that there is a great need to investigate what other factors may contribute to both disease insurgence and phenotypical heterogeneity, and novel evidence are raising the attention toward the study of epigenetics and transcription mechanisms that can influence the disease phenotype beyond genetics. Modulation in the epigenetics machinery including histone modifications, DNA methylation and non-coding RNAs dysregulation, could be crucial players in the development of these disorders, and moreover an aberrant RNA maturation process has been linked to leukodystrophies. Here, we provide an overview of these mechanisms hoping to supply a closer step toward the analysis of leukodystrophies not only as genetically determined but also with an added level of complexity where epigenetic dysregulation is of key relevance. This article is categorized under: Regulatory RNAs/RNAi/Riboswitches > Regulatory RNA RNA in Disease and Development > RNA in Disease RNA in Disease and Development > RNA in Development.

Postnatal Cerebral Hemodynamics and Placental Vascular Malperfusion Lesions in Neonates With Congenital Heart Disease

BackgroundNeonates with congenital heart disease (CHD) have smaller brain volume at birth. High rates of placental vascular malperfusion lesions may play a role in disrupted brain development. MethodsThis is a single-center retrospective cohort study of infants born between 2010 and 2019 who were diagnosed with a major cardiac defect requiring surgery in the first year of life. Doppler ultrasound RI of the middle cerebral artery (MCA) and anterior cerebral artery were calculated within the first 72 hours of life. Placentas were evaluated using a standardized approach. ResultsOver the study period, there were 52 patients with hypoplastic left heart syndrome (HLHS), 22 with single-ventricle right ventricular outflow tract obstruction (SV-RVOTO), 75 with a two-ventricle cardiac defect (2V), and 25 with transposition of the great arteries (TGA). MCA Doppler RI were significantly higher for all subgroups of CHD compared with control subjects (0.68 ± 0.11 in control subjects compared with 0.78 ± 0.13 in HLHS, P = 0.03; 0.77 ± 0.10 in SV-RVOTO, P = 0.002; 0.78 ± 0.13 in 2V, P = 0.03; and 0.80 ± 0.14 in TGA; P = 0.001) with the highest average MCA RI in the TGA group. In subgroup analyses, placental fetal vascular malperfusion in the 2V group was associated with higher MCA RI, but this relationship was not present in other subgroups, nor in regards to maternal vascular malperfusion. ConclusionsMajor forms of CHD are associated with significantly higher cerebral artery RI postnatally, but placental vascular malperfusion lesions may not contribute to this hemodynamic adaptation.

Neurodevelopmental disorders and the role of PSD-95: Understanding pathways and pharmacological interventions

Neurodevelopmental disorders (NDDs) are often linked to disruption in brain development and present challenges for affected individuals in achieving their cognitive, emotional, and motor developmental milestones. NDDs encompass a spectrum of conditions, including autism spectrum disorder (ASD), schizophrenia (SCZ), attention-deficit hyperactivity disorder (ADHD), and epilepsy. The unequivocal diagnosis of an NDD is often challenging due to overlapping signs and symptoms across different conditions. Synaptic plasticity, the activity-driven modification of synaptic strength and efficacy, plays a crucial role in brain network formation and organization and is frequently altered in NDDs. Here, we explore the multifaceted roles of postsynaptic density-95 kDa (PSD-95) in NDDs. Psd-95 is a scaffolding protein belonging to the membrane-associated guanylate kinases (MAGUKs) family, located at the core of synapses, and is central to synaptic plasticity. Dysregulation of PSD-95 is linked to various neuropsychiatric disorders. In SCZ, decreased PSD-95 expression affects synaptic plasticity, thereby impacting learning and memory. Genes associated with ASD interact with PSD-95, and its removal in mice leads to ASD-like behavioral abnormalities. Furthermore, PSD-95 is implicated in ADHD, where its modulation influences neurotransmission. Medications used in NDD treatment, such as antipsychotic drugs and selective serotonin reuptake inhibitors (SSRIs), can alter PSD-95 levels, potentially influencing synapse formation. Alpha-2 adrenergic agonists might enhance synaptic integrity by impacting PSD-95. Alternative pharmacotherapies such as memantine, allopurinol, and ketamine, all influencing PSD-95 to a certain extent, hold promise in managing NDDs. Understanding the role of PSD-95 in these disorders can deepen our biological comprehension and pave the way for targeted therapies. Specifically, exploring how PSD-95 affects synaptic plasticity and dendritic spine development could uncover opportunities for repurposing drugs to treat NDDs associated with mutations in the DLG4 gene encoding PSD-95.

Neonatal stress disrupts the glymphatic system development and increases the susceptibility to Parkinson's disease in later life.

Neonatal stress disrupts brain development and increases the risk of neurological disorders later in life. However, the impact of neonatal stress on the development of the glymphatic system and susceptibility to Parkinson's disease (PD) remains largely unknown. Neonatal maternal deprivation (NMD) was performed on mice for 14 consecutive days to model chronic neonatal stress. Adeno-associated virus expressing A53T-α-synuclein (α-syn) was injected into the substantia nigra to establish PD model mice. Glymphatic activity was determined using invivo magnetic resonance imaging, exvivo fluorescence imaging and microplate assay. The transcription and expression of aquaporin-4 (AQP4) and other molecules were evaluated by qPCR, western blotting, and immunofluorescence. Animal's responses to NMD and α-syn overexpression were observed using behavioral tests. Glymphatic activity was impaired in adult NMD mice. AQP4 polarization and platelet-derived growth factor B (PDGF-B) signaling were reduced in the frontal cortex and hippocampus of both young and adult NMD mice. Furthermore, exogenous α-syn accumulation was increased and PD-like symptoms were aggravated in adult NMD mice. The results demonstrated that NMD could disrupt the development of the glymphatic system through PDGF-B signaling and increase the risk of PD later in life, indicating that alleviating neonatal stress could be beneficial in protecting the glymphatic system and reducing susceptibility to neurodegeneration.

HUBUNGAN BERAT BADAN LAHIR RENDAH DENGAN KEJADIAN STUNTING PADA ANAK USIA 1-5 TAHUN DI WILAYAH KERJA PUSKESMAS JORONGAN

Toddlers are individuals or groups of individuals from a population who are within a certain age range. Toddler age can be grouped into three groups, namely infant age groups (0-2 years), toddler groups (2-3 years), and preschool groups (> 3-5 years) (Chandra Juita, 2021). The purpose of this study was to analyze low birth weight with stunting in children aged 1-5 years in the working area of ​​the Jorongan Health Center.The research design used correlational analysis. The population was all children aged 1-5 years and experience LBW in February 2023 as many as 194 people. The research sample included 131 toddlers aged 1-5 years who had LBW according to the inclusion and exclusion criteria in February 2023 used the Random Sampling technique. Collecting data using a questionnaire then the data is processed using SPSS using Chi square. The results of the analysis showed that the majority of respondents who experienced LBW were 130 people (100%), the incidence of stunting was 76 people (58%). while the results of the Chi-Square test between LBW and the incidence of stunting obtained a p-value of 0.000 (p-value) (smaller than 0.05) so there was a significant relationship between the LBW variable and the incidence of One stunting of the causes of stunting in LBW children is influenced by socio-economic factors, such as education level, income, and number of household members which causes chronic nutritional problems, in the short term is disruption of brain development, intelligence, physical growth, and metabolic disorders in the body.

Impact of respiratory viral infections during pregnancy on the neurological outcomes of the newborn: current knowledge.

Brain development is a complex process that begins during pregnancy, and the events occurring during this sensitive period can affect the offspring's neurodevelopmental outcomes. Respiratory viral infections are frequently reported in pregnant women, and, in the last few decades, they have been related to numerous neuropsychiatric sequelae. Respiratory viruses can disrupt brain development by directly invading the fetal circulation through vertical transmission or inducing neuroinflammation through the maternal immune activation and production of inflammatory cytokines. Influenza virus gestational infection has been consistently associated with psychotic disorders, such as schizophrenia and autism spectrum disorder, while the recent pandemic raised some concerns regarding the effects of severe acute respiratory syndrome coronavirus 2 on neurodevelopmental outcomes of children born to affected mothers. In addition, emerging evidence supports the possible role of respiratory syncytial virus infection as a risk factor for adverse neuropsychiatric consequences. Understanding the mechanisms underlying developmental dysfunction allows for improving preventive strategies, early diagnosis, and prompt interventions.

The Emerging Landscape of the Cerebellum after a Pediatric Traumatic Brain Injury: From Diaschisis to Sociality.

There is an expanding interest in the cerebellum in the context of focal and diffuse traumatic injuries to the cerebral cortex. In the adult brain, preclinical studies have revealed acute as well as progressive loss of Purkinje cells in the cerebellum coincident with microglial activation. This pathogenesis, remote to the site of the primary injury, is termed "diaschisis." Here we consider traumatic injuries to the developing brain, where the cerebellum likewise undergoes neurodegeneration. As injury is superimposed on a young brain, long-term adverse consequences may reflect diaschisis that is compounded by disruption of brain development.

Age-related changes in the architecture and biochemical markers levels in motor-related cortical areas of SHR rats-an ADHD animal model.

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder whose exact pathophysiology has not been fully understood yet. Numerous studies have suggested disruptions in the cellular architecture and neuronal activity within brain structures of individuals with ADHD, accompanied by imbalances in the immune system, oxidative stress, and metabolism. This study aims to assess two functionally and histologically distinct brain areas involved in motor control and coordination: the motor cortex (MC) and prefrontal cortex (PFC). Namely, the morphometric analysis of the MC throughout the developmental stages of Spontaneously Hypertensive Rats (SHRs) and Wistar Kyoto Rats (WKYs). Additionally, the study aimed to investigate the levels and activities of specific immune, oxidative stress, and metabolic markers in the PFC of juvenile and maturing SHRs in comparison to WKYs. The most significant MC volume reductions occurred in juvenile SHRs, accompanied by alterations in neuronal density in these brain areas compared to WKYs. Furthermore, juvenile SHRs exhibit heightened levels and activity of various markers, including interleukin-1α (IL-1α), IL-6, serine/threonine-protein mammalian target of rapamycin, RAC-alpha serine/threonine-protein kinase, glucocorticoid receptor β, malondialdehyde, sulfhydryl groups, superoxide dismutase, peroxidase, glutathione reductase, glutathione S-transferase, glucose, fructosamine, iron, lactic acid, alanine, aspartate transaminase, and lactate dehydrogenase. Significant changes in the MC morphometry and elevated levels of inflammatory, oxidative, and metabolic markers in PFC might be associated with disrupted brain development and maturation in ADHD.

12 Differential Processing Efficiency Skills in Survivors of Pediatric Primary CNS Cancer and Cancers of non-CNS Origin

Objective:Pediatric cancer and cancer-related treatments may disrupt brain development and place survivors at risk for long term problems with cognitive functions. Processing efficiency has been operationalized as a nuanced cognitive skill that reflects both processing speed (PS) and working memory (WM) abilities and is sensitive to neurobiological disruption. Pediatric cancer survivors are at risk for processing efficiency deficits; however, a thorough characterization of processing efficiency skills across pediatric primary central nervous system (CNS) tumor and non-CNS cancer survivors has not yet been reported.Participants and Methods:Participants were selected from a mixed retrospective clinical database of pediatric cancer survivors (Total n=160; primary CNS tumor n=33; Non-CNS n=127). Univariate analyses were conducted to examine differences in processing efficiency mean scores (t-tests) and percent impairment (scores >1 SD below mean; chi-squared tests) between the total sample and normative sample, and across groups (CNS vs. Non-CNS). Multiple linear regressions were utilized to evaluate the relationships between additional risk factors, including biological sex, age at diagnosis, time since treatment, and socioeconomic status, and processing efficiency outcomes.Results:The total sample obtained lower scores on WM (M=90.83, SD=13.35) and PS (M=88.86, SD=14.38) measures than normative samples (M=100, SD=15), p < 0.001. Greater percentage of pediatric cancer survivors demonstrated impairment across all processing efficiency measures (24.8-38.1%) than normative samples (15.9%), p < 0.001. Regarding group differences, the CNS group obtained lower mean WM (M=84.85, SD =11.77) and PS (M=80, SD=14.18) scores than the Non-CNS group (WM M=92.39, SD=13.32; PS M=91.16, SD=13.56), p < 0.001. Rates of impairment between groups only differed for PS scores, with 63.6% of the CNS group and 31.5% of the non-CNS group demonstrating impairment, p < 0.001. Primary CNS tumor cancer type and male biological sex emerged as the only significant risk factors that predicted processing efficiency skills, with male sex predicting lower scores on PS (ß=8.91 p<.001) and semantic fluency (ß=7.59, p=.007).Conclusions:These findings indicate that both pediatric primary CNS tumor and non-CNS cancer survivors exhibit substantial weaknesses in processing efficiency skills after treatment. While both groups demonstrated deficits compared to normative samples, the CNS group was more susceptible to PS impairments than non-CNS group. A basic initial study of the relationships between risk factors and processing efficiency skills revealed that primary CNS cancer was a predictor of lower performance on working memory and processing speed measures, while male biological sex was a significant risk factor for worse performance on processing speed and semantic fluency measures. Continued focus on the construct of processing efficiency in pediatric cancer survivors is warranted. Applying a standardized approach to assessing and communicating this nuanced cognitive skill could contribute to advancing both clinical practice and outcomes research of pediatric cancer survivors.

Romania’s Abandoned Children: The Effects of Early Profound Psychosocial Deprivation on the Course of Human Development

Understanding the impact that early psychosocial neglect has on the course of human development has implications for the millions of children around the world who are living in contexts of adversity. In the United States, approximately 76% of cases reported to child protective services involve neglect; worldwide, there are more than 150 million orphaned or abandoned children, including 10.5 million orphaned because of COVID-19. In much of the world, children without primary caregivers are reared in institutional settings. We review two decades of research based on the only randomized controlled trial of foster care as an alternative to institutional care. We report that children randomly assigned to continued care as usual (institutional care) suffer from persistent deficits in social, cognitive, and emotional development and show evidence of disruptions in brain development. By contrast, children randomly assigned to foster care show improvements in most domains of functioning, although the degree of recovery is in part a function of how old they were when placed into foster care and the stability of that placement. These findings have important implications for understanding critical periods in human development as well as elucidate the power of the psychosocial environment in shaping multiple domains of human development.

Exposure to polystyrene particles causes anxiety-, depression-like behavior and abnormal social behavior in mice

In the era of plastic use, organisms are constantly exposed to polystyrene particles (PS-Ps). PS-Ps accumulated in living organisms exert negative effects on the body, although studies evaluating their effects on brain development are scarce. In this study, the effects of PS-Ps on nervous system development were investigated using cultured primary cortical neurons and mice exposed to PS-Ps at different stages of brain development. The gene expression associated with brain development was downregulated in embryonic brains following PS-Ps exposure, and Gabra2 expression decreased in the embryonic and adult mice exposed to PS-Ps. Additionally, offspring of PS-Ps-treated dams exhibited signs of anxiety- and depression-like behavior, and abnormal social behavior. We propose that PS-Ps accumulation in the brain disrupts brain development and behavior in mice. This study provides novel information regarding PS-Ps toxicity and its harmful effects on neural development and behavior in mammals.

A comparative assessment of most widely used machine learning classifiers for analysing and classifying autism spectrum disorder in toddlers and adolescents

Individuals with autism spectrum disorder (ASD) have social interaction and communication challenges due to a disruption in brain development that impacts how they perceive and interact with others. The symptoms of autism often present themselves within the first two years of a persons life but can be diagnosed at any time. The ASD theory suggests that the onset of symptoms occurs in early childhood and persists until young adulthood. Machine learning research has been applied to the study of autism. We use Machine Learning (ML) methods and technologies, including Naive Bayes (NB) classifiers, Logistic Regression (LR), Support Vector Machine (SVM), and Random Forest (RF) to analyse and predict ASD in toddlers (kids between 12 to 36 months old) and adolescents (children between 12 to 18 years old) using non-clinical ASD datasets. In this paper, we review the literature and conduct an in-depth investigation of supervised machine-learning algorithms to evaluate the effectiveness of four leading classifiers on a dataset used for ASD screening.

Lactobacillus fermentum HNU312 alleviated oxidative damage and behavioural abnormalities during brain development in early life induced by chronic lead exposure

Lead exposure is a global public health safety issue that severely disrupts brain development and causes damage to the nervous system in early life. Probiotics and gut microbes have been highlighted for their critical roles in mitigating lead toxicity. However, the underlying mechanisms by which they work yet to be fully explored. Here, we designed a two-stage experiment using the probiotic Lactobacillus fermentum HNU312 (Lf312) to uncover how probiotics alleviate lead toxicity to the brain during early life. First, we explored the tolerance and adsorption of Lf312 to lead in vitro. Second, the adsorption capacity of the strain was determined and confirmed in vivo. The shotgun metagenome sequencing showed lead exposure-induced imbalance and dysfunction of the gut microbiome. In contrast, Lf312 intake significantly modulated the structure of the microbiome, increased the abundance of beneficial bacteria and short-chain fatty acids (SCFAs)-producing bacteria, and upregulated function-related metabolic pathways such as antioxidants. Notably, Lf312 enhanced the integrity of the blood-brain barrier by increasing the levels of SCFAs in the gut, alleviated inflammation in the brain, and ultimately improved anxiety-like and depression-like behaviours induced by lead exposure in mice. Subsequently, the effective mechanism was confirmed, highlighting that Lf312 worked through integrated strategies, including ionic adsorption and microbiota-gut-brain axis regulation. Collectively, this work elucidated the mechanism by which the gut microbiota mitigates the toxic effects of lead in the brain and provides preventive measures and intervention measures for brain damage due to mass lead poisoning in children.