Neurodevelopmental processes represent a finely tuned interplay between genetic and environmental factors,shaping the dynamic landscape of the developing brain.A major component of the developing brain that enables th...Neurodevelopmental processes represent a finely tuned interplay between genetic and environmental factors,shaping the dynamic landscape of the developing brain.A major component of the developing brain that enables this dynamic is the white matter(WM),known to be affected in neurodevelopmental disorders(NDDs)(Rokach et al.,2024).WM formation is mediated by myelination,a multifactorial process driven by neuro-glia interactions dependent on proper neuronal functionality(Simons and Trajkovic,2006).Another key aspect of neurodevelopmental abnormalities involves neuronal dynamics and function,with recent advances significantly enhancing our understanding of both neuronal and glial mitochondrial function(Devine and Kittler,2018;Rojas-Charry et al.,2021).Energy homeostasis in neurons,attributed largely to mitochondrial function,is critical for proper functionality and interactions with oligodendrocytes(OLs),the cells forming myelin in the brain’s WM.We herein discuss the interplay between these processes and speculate on potential dysfunction in NDDs.展开更多
Introduction Congenital heart disease(CHD)is the most common birth defect with complex CHD contributing to 20%–30%of this disease[1].Overall survival rates of cCHD have improved substantially,thanks to remarkable pro...Introduction Congenital heart disease(CHD)is the most common birth defect with complex CHD contributing to 20%–30%of this disease[1].Overall survival rates of cCHD have improved substantially,thanks to remarkable progress in surgical techniques and perioperative care over the past three decades.In-hospital mortality rate during 2017–2021 for CHD-associated surgery in China is approximately 0.8%–1.0% and 2.5%–3.8% for complex CHD[2].Brain injury and later neurodevelopmental impairment(NDI)are the most enduring and detrimental complications for patients with complex CHD.As a growing number of individuals with complex CHD survive into adulthood,the impact and high incidence of NDI should be addressed.Moreover,there needs to be a research shift from improving survival to improving whole life quality,particularly in perioperative neuroprotection,persistent neurodevelopmental evaluation and early intervention.展开更多
Schizophrenia is a complex neuropsychiatric disorder marked by positive symptoms(hallucinations,delusions),negative symptoms(affective flattening,social withdrawal),and cognitive deficits.Its etiology reflects both st...Schizophrenia is a complex neuropsychiatric disorder marked by positive symptoms(hallucinations,delusions),negative symptoms(affective flattening,social withdrawal),and cognitive deficits.Its etiology reflects both strong genetic liability and environmental influences during critical stages of brain development.Dermatoglyphics,the study of epidermal ridge patterns on fingers,palms,and soles,forms between the 10th and 16th weeks of gestation,a key neurodevelopmental period.Because both the epidermis and central nervous system share an ectodermal origin,disturbances during this window may produce parallel alterations in ridge patterns and brain structure.Interest in anthropometric markers of psychiatric illness dates to the 19th century,when theories of degeneracy proposed physical anomalies as signs of hereditary vulnerability.Although controversial,dermatoglyphics has recently re-emerged as a potential non-invasive biomarker for schizophrenia.This review synthesizes evidence on dermatoglyphic patterns in schizophrenia,emphasizing twin studies,comparisons with bipolar disorder,and integration with related developmental anomalies such as minor physical anomalies and somatotype.A structured search of PubMed and Scopus(January 2004 to December 2024)identified 83 eligible studies.Inclusion criteria encompassed original human research,reviews,or meta-analyses on dermatoglyphics in schizophrenia or related psychotic disorders,while excluding animal studies,non-quantitative case reports,and non-English papers without translation.Consistent findings include reduced total ridge counts,increased fluctuating asymmetry,and greater prevalence of abnormal palmar flexion creases among individuals with schizophrenia.Twin designs show anomalies are more frequent in affected co-twins,even among monozygotic pairs,underscoring prenatal environmental effects.Comparative work suggests schizophrenia and bipolar disorder share some but not all dermatoglyphic alterations,offering potential diagnostic value.Dermatoglyphic analysis is stable,inexpensive,and non-invasive,supporting its promise as an adjunctive biomarker of neurodevelopmental disruption.However,methodological variability and limited standardization currently restrict clinical application.Future research should harmonize measurement techniques and integrate genomic and neuroimaging correlates.展开更多
Neuroinflammation is the primary driver and signature of many neurodevelopmental disorders.However,because neurodevelopmental disorders caused by neuroinflammation are difficult to detect at the early stage,their prog...Neuroinflammation is the primary driver and signature of many neurodevelopmental disorders.However,because neurodevelopmental disorders caused by neuroinflammation are difficult to detect at the early stage,their progression remains unclear.To date,neither animal experiments nor in vitro models have uncovered their early developmental characteristics caused by neuroinflammation.In this study,we developed a neurovascular-unit-on-a-chip(NVU-on-a-chip)to model inflammation-induced neurodevelopmental disorders.With the chip,dynamic visualization of the progression caused by neuroinflammation was clearly demonstrated,and the changes in angiogenesis and neural differentiation under neuroinflammation were replicated.In addition,the activation of astrocytes and damage to neurons and capillaries at the early stage of neurodevelopmental disorders were observed.The results revealed for the first time the structural disruption of the neurovascular units and the neurovascular coupling failure caused by neuroinflammation.Furthermore,the outcomes of anti-inflammatory intervention using ibuprofen were preliminarily demonstrated.This work provides insights into the early progression of neurodevelopmental disorders caused by neuroinflammation and offers a platform for the development of therapeutic strategies for neuroinflammation.展开更多
GEMIN5 is a predominantly cytoplasmic multifunctional protein, known to be involved in recognizing snRNAs through its WD40 repeats domain placed at the N-terminus. A dimerization domain in the middle region acts as a ...GEMIN5 is a predominantly cytoplasmic multifunctional protein, known to be involved in recognizing snRNAs through its WD40 repeats domain placed at the N-terminus. A dimerization domain in the middle region acts as a hub for protein–protein interaction, while a non-canonical RNA-binding site is placed towards the C-terminus. The singular organization of structural domains present in GEMIN5 enables this protein to perform multiple functions through its ability to interact with distinct partners, both RNAs and proteins. This protein exerts a different role in translation regulation depending on its physiological state, such that while GEMIN5 down-regulates global RNA translation, the C-terminal half of the protein promotes translation of its mRNA. Additionally, GEMIN5 is responsible for the preferential partitioning of mRNAs into polysomes. Besides selective translation, GEMIN5 forms part of distinct ribonucleoprotein complexes, reflecting the dynamic organization of macromolecular complexes in response to internal and external signals. In accordance with its contribution to fundamental cellular processes, recent reports described clinical loss of function mutants suggesting that GEMIN5 deficiency is detrimental to cell growth and survival. Remarkably, patients carrying GEMIN5 biallelic variants suffer from neurodevelopmental delay, hypotonia, and cerebellar ataxia. Molecular analyses of individual variants, which are defective in protein dimerization, display decreased levels of ribosome association, reinforcing the involvement of the protein in translation regulation. Importantly, the number of clinical variants and the phenotypic spectrum associated with GEMIN5 disorders is increasing as the knowledge of the protein functions and the pathways linked to its activity augments. Here we discuss relevant advances concerning the functional and structural features of GEMIN5 and its separate domains in RNA-binding, protein interactome, and translation regulation, and how these data can help to understand the involvement of protein malfunction in clinical variants found in patients developing neurodevelopmental disorders.展开更多
Mitochondrial dysfunction has emerged as a critical factor in the etiology of various neurodevelopmental disorders, including autism spectrum disorders, attention-deficit/hyperactivity disorder, and Rett syndrome. Alt...Mitochondrial dysfunction has emerged as a critical factor in the etiology of various neurodevelopmental disorders, including autism spectrum disorders, attention-deficit/hyperactivity disorder, and Rett syndrome. Although these conditions differ in clinical presentation, they share fundamental pathological features that may stem from abnormal mitochondrial dynamics and impaired autophagic clearance, which contribute to redox imbalance and oxidative stress in neurons. This review aimed to elucidate the relationship between mitochondrial dynamics dysfunction and neurodevelopmental disorders. Mitochondria are highly dynamic organelles that undergo continuous fusion and fission to meet the substantial energy demands of neural cells. Dysregulation of these processes, as observed in certain neurodevelopmental disorders, causes accumulation of damaged mitochondria, exacerbating oxidative damage and impairing neuronal function. The phosphatase and tensin homolog-induced putative kinase 1/E3 ubiquitin-protein ligase pathway is crucial for mitophagy, the process of selectively removing malfunctioning mitochondria. Mutations in genes encoding mitochondrial fusion proteins have been identified in autism spectrum disorders, linking disruptions in the fusion-fission equilibrium to neurodevelopmental impairments. Additionally, animal models of Rett syndrome have shown pronounced defects in mitophagy, reinforcing the notion that mitochondrial quality control is indispensable for neuronal health. Clinical studies have highlighted the importance of mitochondrial disturbances in neurodevelopmental disorders. In autism spectrum disorders, elevated oxidative stress markers and mitochondrial DNA deletions indicate compromised mitochondrial function. Attention-deficit/hyperactivity disorder has also been associated with cognitive deficits linked to mitochondrial dysfunction and oxidative stress. Moreover, induced pluripotent stem cell models derived from patients with Rett syndrome have shown impaired mitochondrial dynamics and heightened vulnerability to oxidative injury, suggesting the role of defective mitochondrial homeostasis in these disorders. From a translational standpoint, multiple therapeutic approaches targeting mitochondrial pathways show promise. Interventions aimed at preserving normal fusion-fission cycles or enhancing mitophagy can reduce oxidative damage by limiting the accumulation of defective mitochondria. Pharmacological modulation of mitochondrial permeability and upregulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, an essential regulator of mitochondrial biogenesis, may also ameliorate cellular energy deficits. Identifying early biomarkers of mitochondrial impairment is crucial for precision medicine, since it can help clinicians tailor interventions to individual patient profiles and improve prognoses. Furthermore, integrating mitochondria-focused strategies with established therapies, such as antioxidants or behavioral interventions, may enhance treatment efficacy and yield better clinical outcomes. Leveraging these pathways could open avenues for regenerative strategies, given the influence of mitochondria on neuronal repair and plasticity. In conclusion, this review indicates mitochondrial homeostasis as a unifying therapeutic axis within neurodevelopmental pathophysiology. Disruptions in mitochondrial dynamics and autophagic clearance converge on oxidative stress, and researchers should prioritize validating these interventions in clinical settings to advance precision medicine and enhance outcomes for individuals affected by neurodevelopmental disorders.展开更多
Critical periods(CPs)are defined as postnatal developmental windows during which brain circuits exhibit heightened sensitivity to altered experiences or sensory inputs,particularly during brain development in humans a...Critical periods(CPs)are defined as postnatal developmental windows during which brain circuits exhibit heightened sensitivity to altered experiences or sensory inputs,particularly during brain development in humans and animals.During the CP,experience-induced refinements of neural connections are crucial for establishing adaptive and mature brain functions,and aberrant CPs are often accompanied by many neurodevelopmental disorders(NDDs),including autism spectrum disorders and schizophrenia.Understanding neural mechanisms underlying the CP regulation is key to delineating the etiology of NDDs caused by abnormal postnatal neurodevelopment.Recent evidence from studies using innovative experimental tools has continuously revisited the inhibition-gating theory of CP to systematically elucidate the differential roles of distinct inhibitory circuits.Here,we provide a comprehensive review of classical experimental findings and emerging inhibitory-circuit regulation mechanisms of the CP,and further discuss how aberrant CP plasticity is associated with NDDs.展开更多
Maternal health during pregnancy has a direct impact on the risk and severity of neurodevelopmental disorders(NDDs)in the offspring,especially in the case of drug exposure.However,little progress has been made to asse...Maternal health during pregnancy has a direct impact on the risk and severity of neurodevelopmental disorders(NDDs)in the offspring,especially in the case of drug exposure.However,little progress has been made to assess the risk of drug exposure during pregnancy due to ethical constraints and drug use factors.We collected and manually curated sub-pathways and pathways(sub-/pathways)and drug information to propose an analytical framework for predicting drug candidates.This framework linked sub-/pathway activity and drug response scores derived from gene transcription data and was applied to human fetal brain development and six NDDs.Further,specific and pleiotropic sub-/pathways/drugs were identified using entropy,and sex bias was analyzed in conjunction with logistic regression and random forest models.We identified 19 disorder-associated and 256 regionally pleiotropic and specific candidate drugs that targeted risk sub-/pathways in NDDs,showing temporal or spatial changes across fetal development.Moreover,5443 differential drug-sub-/pathways exhibited sex-biased differences after filling in the gender labels.A user-friendly NDDP visualization website(https://ndd-lab.shinyapps.io/NDDP)was developed to allow researchers and clinicians to access and retrieve data easily.Our framework overcame data gaps and identified numerous pleiotropic and specific candidates across six disorders and fetal developmental trajectories.This could significantly contribute to drug discovery during pregnancy and can be applied to a wide range of traits.展开更多
BACKGROUND Neurodevelopmental delays encompass a wide range of conditions that impair cognitive,motor,and social functioning,often increasing the risk of psychiatric comorbidities.Children with these delays frequently...BACKGROUND Neurodevelopmental delays encompass a wide range of conditions that impair cognitive,motor,and social functioning,often increasing the risk of psychiatric comorbidities.Children with these delays frequently present with disorders such as attention-deficit/hyperactivity disorder(ADHD),anxiety,and behavioral disturbances,which can significantly affect development and quality of life.While genetic predisposition has been linked to these comorbidities,growing evidence highlights the role of environmental factors,including prenatal and early-life stressors.However,the interaction between genetic susceptibility and environmental influences remains poorly understood.Identifying specific genetic variants,environmental risks,and their interactions is essential for early detection and targeted interventions.AIM To investigate the combined effects of genetic and environmental factors on psychiatric comorbidities in children with neurodevelopmental delays,elucidate underlying mechanisms,and inform clinical management strategies.METHODS This retrospective cohort study included 80 children with confirmed neurodevelopmental delays and 40 age-and sex-matched typically developing controls.Comprehensive clinical and psychiatric evaluations,genetic testing(chromosomal microarray analysis and targeted next-generation sequencing),and environmental exposure assessments were conducted.Statistical analyses explored associations between genetic variants and psychiatric comorbidities,environmental risk factors,and gene-environment interactions.RESULTS Children with neurodevelopmental delays exhibited significantly higher rates of psychiatric comorbidities(70.0%)compared to controls(15.0%),with ADHD(42.5%),anxiety disorders(28.8%),and behavioral disorders(23.8%)being the most common.Pathogenic genetic variants were identified in specific pathways associated with distinct psychiatric presentations:Glutamatergic signaling variants were linked to anxiety disorders(odds ratio=3.8),dopaminergic system variants to ADHD(odds ratio=4.2),and synaptic function variants to both behavioral and anxiety disorders.Environmental factors,particularly prenatal maternal stress,early childhood adversity,and family dysfunction were strong predictors of psychiatric outcomes(β=0.42).Significant gene-environment interactions were identified,indicating that environmental exposure can moderate the effects of genetic risks on psychiatric outcomes.CONCLUSION Psychiatric comorbidities in children with neurodevelopmental delays are significantly influenced by both genetic and environmental factors,with complex interactions between the two.These findings underscore the need for integrated assessments and targeted interventions addressing both biological and environmental contributors to improve outcomes in this vulnerable population.展开更多
The impact of mother-infant microbiota on neurodevelopment is an area of interest,but longitudinal studies are scarce.Using a cohort of 520 families from the Jiangsu birth cohort in China,we reveal that the maternal g...The impact of mother-infant microbiota on neurodevelopment is an area of interest,but longitudinal studies are scarce.Using a cohort of 520 families from the Jiangsu birth cohort in China,we reveal that the maternal gut microbiota during early pregnancy play a substantial role,accounting for 3.34%of the variance in offspring neurodevelopmental scores.This contribution is notably higher than the 1.24%attributed to the infants’own microbiota at 1 year of age,underscoring the significant influence of maternal gut health on early child development.Remarkably,an elevation in maternal Bifidobacterium pseudocatenulatum is linked to decreased cognitive scores,whereas an enrichment of Bifidobacterium longum at 1 year of age is associated with higher cognitive scores.Furthermore,we find that maternal B.pseudocatenulatum is linked to the heterolactic fermentation metabolic pathway,while infant B.longum is associated with the Bifidobacterium shunt pathway.In summary,our analysis implies that maternal and infant gut microbiota play a distinct role in neurodevelopment,suggesting potential strategies for improving neurodevelopmental outcomes during early pregnancy or infant development by targeting gut microbiota composition.展开更多
Background:The life-course management of children with tetralogy of Fallot(TOF)has focused on demonstrating brain structural alterations,developmental trajectories,and cognition-related changes that unfold over time.M...Background:The life-course management of children with tetralogy of Fallot(TOF)has focused on demonstrating brain structural alterations,developmental trajectories,and cognition-related changes that unfold over time.Methods:We introduce an magnetic resonance imaging(MRI)dataset comprising TOF children who underwent brain MRI scanning and cross-sectional neurocognitive follow-up.The dataset includes brain three-dimensional T1-weighted imaging(3D-T1WI),three-dimensional T2-weighted imaging(3D-T2WI),and neurodevelopmental evaluations using the Wechsler Preschool and Primary Scale of Intelligence–Fourth Edition(WPPSI-IV).Results:Thirty-one children with TOF(age range:4–33 months;18 males)were recruited and completed corrective surgery at the Children’s Hospital of Nanjing Medical University,Nanjing,China.Aiming to promote the neurodevelopmental outcomes in children with TOF,we have meticulously curated a comprehensive dataset designed to dissect the complex interplay among risk factors,neuroimaging findings,and adverse neurodevelopmental outcomes.Conclusion:This article aims to introduce our open-source dataset on neurodevelopment in children with TOF,which covers the data types,data acquisition and processing methods,the procedure for accessing the data,and related publications.展开更多
Background: Spinal dysraphism represents a wide spectrum of congenital abnormalities of the spine. Myelomeningocele is considered the most common malformation and the most common we saw in our community, with its morb...Background: Spinal dysraphism represents a wide spectrum of congenital abnormalities of the spine. Myelomeningocele is considered the most common malformation and the most common we saw in our community, with its morbidity problems seen commonly in the postoperative period. ASQ-3<sup>TM</sup> Scores are the ages and stages questionnaire, third edition, and represent a tool to assess the development progress, especially in toddlers. Objectives: Evaluation of neurodevelopmental outcome among Sudanese toddlers with spinal dysraphism after surgical closure with or without a VP shunt using ASQ-3<sup>TM</sup> Scores. Methodology: This is a retrospective hospital-based study of 84 patients who underwent myelomeningocele repair at the National Center for Neurological Sciences (NCNS) during the period from 2017 up to 2019. Data were collected through a constructed questionnaire, including ASQ-3<sup>TM</sup> Scores. Data were processed and analyzed using the Statistical Package for Social Science (SPSS) computer program. Version 25. Results: 84 patients were included in this study;all patients were diagnosed with spinal dysraphism. Out of them, 51 (60.7%) were 2 years old, 33 (39.3%) were 3 years old, 45 (53.6%) were male, 45 (53.6%) of patients mothers attended ANC irregularly, and 54 (64.3%) their mothers didn’t receive folate supplements. 44 (52.3%) of patients underwent MMC repair only, while 40 (47.7%) underwent MMC repair and VP shunt. The commonest postoperative complication was infection, reported in 12 (14.3%) of patients, followed by VP shunt revision in 9 (10.7%) of patients. Neurological assessment showed that the majority of patients need further assessment with a professional, 57 (67.9%) of children don’t walk, run, or climb like other toddlers as their parent’s state;also, half of patients (42, 50%) had medical problems, and 27 (32.1%) of their parent’s state that they do not talk like other toddlers their age. There was a statistically significant association between post-operative complications and communication development, problem-solving development, and personal social development (P value = 0.05), and a statistically significant association was found between age at repair and neurological development (P value = 0.05). Conclusion: The majority of patients had motor deficiency (particularly gross motor) and poor personal and social skills. Age at repair and postoperative complications significantly influenced the neurological development.展开更多
The recent identification of a neurodevelopmental disorder with cerebellar atrophy and motor dysfunction(NEDCAM)has resulted in an increased interest in GEMIN5,a multifunction RNA-binding protein.As the largest member...The recent identification of a neurodevelopmental disorder with cerebellar atrophy and motor dysfunction(NEDCAM)has resulted in an increased interest in GEMIN5,a multifunction RNA-binding protein.As the largest member of the survival motor neuron complex,GEMIN5 plays a key role in the biogenesis of small nuclear ribonucleoproteins while also exhibiting translational regulatory functions as an independent protein.Although many questions remain regarding both the pathogenesis and pathophysiology of this new disorder,considerable progress has been made in the brief time since its discovery.In this review,we examine GEMIN5 within the context of NEDCAM,focusing on the structure,function,and expression of the protein specifically in regard to the disorder itself.Additionally,we explore the current animal models of NEDCAM,as well as potential molecular pathways for treatment and future directions of study.This review provides a comprehensive overview of recent advances in our understanding of this unique member of the survival motor neuron complex.展开更多
Objective: This study aimed to assess perinatal morbidity, mortality rates, and neurodevelopmental outcomes in the management of fetal growth restriction (FGR) at a single tertiary institute. Methods: Among 2465 deliv...Objective: This study aimed to assess perinatal morbidity, mortality rates, and neurodevelopmental outcomes in the management of fetal growth restriction (FGR) at a single tertiary institute. Methods: Among 2465 deliveries between 2013 and 2019, 109 cases of FGR were reviewed retrospectively for causes, indications for pregnancy termination, perinatal death, overall neonatal outcomes, and long-term prognosis. Results: Excluding FGR due to congenital anomalies (n = 17), the mortality rate was 3.3% (3/92). One neonate delivered at 23 weeks developed cerebral palsy (1.1%). Retinopathy of prematurity occurred in four neonates (4.3%). Neurodevelopmental disorders were present in six neonates (6.5%), all of whom were delivered at 32 - 38 weeks. Significantly lower gestational age at delivery, lower birth weight, and higher umbilical artery resistance indices were observed in neonates with neurodevelopmental disorders. Conclusions: Intact survival before 27 weeks of gestation at delivery with FGR is uncommon. Neurodevelopmental disorders may still develop after delivery at 32 - 38 weeks;consideration should be given to the timing of delivery usingfetal ductus venosus Doppler waveforms measurements to reduce neurodevelopmental disorders.展开更多
Tributyltin(TBT),a common organotin environmental pollutant,may pose a threat to human development during critical early-life periods.We aimed to assess the neurodevelopmental intergenerational toxicity of early-life ...Tributyltin(TBT),a common organotin environmental pollutant,may pose a threat to human development during critical early-life periods.We aimed to assess the neurodevelopmental intergenerational toxicity of early-life exposure to TBT and the protective effect of DNA methyl donor folic acid(FA).Specifically,after early-life exposure(1–21 days postfertilization,dpf)to TBT(0,1,10 and 100 ng/L),zebrafish(Danio rerio)were cultured in clean medium until sexual maturity.The exposed females were mated with unexposed males to produce embryos(F1).The F1 generation were cultured(4–120 hours post-fertilization,hpf)with and without 1 mmol/L FA.The neurotoxic effects of early-life TBT exposure for zebrafish and their offspring(F1)were significantly enhanced anxiety and reduced aggression,decreased gene expression of DNA methyltransferase in the brain and increased serotonin levels in the body.Moreover,the intergenerational neurodevelopmental toxicity,as manifested in the F1 generation,was attenuated by FA supplementation.In summary,early-life TBT exposure led to intergenerational neurodevelopmental deficits in zebrafish,and DNA methyl donors had a protective effect on F1 neurodevelopment,which can inform the prevention and treatment of intergenerational neurotoxicity due to organotin pollutants.展开更多
Neurodevelopmental disorders are characterized by an abnormal development of the central nervous system, leading to a myriad of symptoms and diseases, including intellectual disability, attention deficits, impairments...Neurodevelopmental disorders are characterized by an abnormal development of the central nervous system, leading to a myriad of symptoms and diseases, including intellectual disability, attention deficits, impairments in learning and memory, speech disorders and repetitive behavior （Telias and Ben-Yosef, 2014）. Common major neurodevelopmental disorders include autism and autism spectrum disorders （ASDs）, fragile X syndrome （FXS）, Down syndrome （DS）, and Rett syndrome （RTT）. They can be collectively described as disorders in which the plasticity of the brain has been severely impaired. The concept of plasticity refers to the brain＇s ability to adapt to and process new information and react accordingly, and it can be classified into three categories： a） molecular plasticity, whenever specific receptors, ion channels, enzymes,展开更多
Autism spectrum disorder(ASD)is a group of neurodevelopmental disorders that cause severe social,communication,and behavioral problems.Recent studies show that the variants of a histone methyltransferase gene KMT5B ca...Autism spectrum disorder(ASD)is a group of neurodevelopmental disorders that cause severe social,communication,and behavioral problems.Recent studies show that the variants of a histone methyltransferase gene KMT5B cause neurodevelopmental disorders(NDDs),including ASD,and the knockout of Kmt5b in mice is embryonic lethal.However,the detailed genotype-phenotype correlations and functional effects of KMT5B in neurodevelopment are unclear.By targeted sequencing of a large Chinese ASD cohort,analyzing published genome-wide sequencing data,and mining literature,we curated 39 KMT5B variants identified from NDD individuals.A genotype-phenotype correlation analysis for 10 individuals with KMT5B pathogenic variants reveals common symptoms,including ASD,intellectual disability,languages problem,and macrocephaly.In vitro knockdown of the expression of Kmt5b in cultured mouse primary cortical neurons leads to a decrease in neuronal dendritic complexity and an increase in dendritic spine density,which can be rescued by expression of human KMT5B but not that of pathogenic de novo missense mutants.In vivo knockdown of the Kmt5b expression in the mouse embryonic cerebral cortex by in utero electroporation results in decreased proliferation and accelerated migration of neural progenitor cells.Our findings reveal essential roles of histone methyltransferase KMT5B in neuronal development,prenatal neurogenesis,and neuronal migration.展开更多
Vascular endothelial growth factor（VEGF）in neurodevelopment and regeneration：VEGF is a well-known factor that promotes vascularization and angiogenesis.Besides this it participates in the pathogenesis of several di...Vascular endothelial growth factor（VEGF）in neurodevelopment and regeneration：VEGF is a well-known factor that promotes vascularization and angiogenesis.Besides this it participates in the pathogenesis of several diseases,such as colorectal carcinoma,lung cancer or diabetic retinopathy.Within the last decade,VEGF has been successfully integrated into the treatment of such diseases,for example as a therapy for colorectal cancer with the VEGF-receptor （VEGFR）-inhibitor axitinib.展开更多
Mice use ultrasonic vocalizations(USVs)to communicate each other and to convey their emotional state.USVs have been greatly characterized in specific life phases and contexts,such as mother isolation-induced USVs for ...Mice use ultrasonic vocalizations(USVs)to communicate each other and to convey their emotional state.USVs have been greatly characterized in specific life phases and contexts,such as mother isolation-induced USVs for pups or female-induced USVs for male mice during courtship.USVs can be acquired by means of specific tools and later analyzed on the base of both quantitative and qualitative parameters.Indeed,different ultrasonic call categories exist and have already been defined.The understanding of different calls meaning is still missing,and it will represent an essential step forward in the field of USVs.They have long been studied in the ethological context,but recently they emerged as a precious instrument to study pathologies characterized by deficits in communication,in particular neurodevelopmental disorders(NDDs),such as autism spectrum disorders.This review covers the topics of USVs characteristics in mice,contexts for USVs emission and factors that modulate their expression.A particular focus will be devoted to mouse USVs in the context of NDDs.Indeed,several NDDs murine models exist and an intense study of USVs is currently in progress,with the aim of both performing an early diagnosis and to find a pharmacological/behavioral intervention to improve patients’quality of life.展开更多
文摘Neurodevelopmental processes represent a finely tuned interplay between genetic and environmental factors,shaping the dynamic landscape of the developing brain.A major component of the developing brain that enables this dynamic is the white matter(WM),known to be affected in neurodevelopmental disorders(NDDs)(Rokach et al.,2024).WM formation is mediated by myelination,a multifactorial process driven by neuro-glia interactions dependent on proper neuronal functionality(Simons and Trajkovic,2006).Another key aspect of neurodevelopmental abnormalities involves neuronal dynamics and function,with recent advances significantly enhancing our understanding of both neuronal and glial mitochondrial function(Devine and Kittler,2018;Rojas-Charry et al.,2021).Energy homeostasis in neurons,attributed largely to mitochondrial function,is critical for proper functionality and interactions with oligodendrocytes(OLs),the cells forming myelin in the brain’s WM.We herein discuss the interplay between these processes and speculate on potential dysfunction in NDDs.
文摘Introduction Congenital heart disease(CHD)is the most common birth defect with complex CHD contributing to 20%–30%of this disease[1].Overall survival rates of cCHD have improved substantially,thanks to remarkable progress in surgical techniques and perioperative care over the past three decades.In-hospital mortality rate during 2017–2021 for CHD-associated surgery in China is approximately 0.8%–1.0% and 2.5%–3.8% for complex CHD[2].Brain injury and later neurodevelopmental impairment(NDI)are the most enduring and detrimental complications for patients with complex CHD.As a growing number of individuals with complex CHD survive into adulthood,the impact and high incidence of NDI should be addressed.Moreover,there needs to be a research shift from improving survival to improving whole life quality,particularly in perioperative neuroprotection,persistent neurodevelopmental evaluation and early intervention.
文摘Schizophrenia is a complex neuropsychiatric disorder marked by positive symptoms(hallucinations,delusions),negative symptoms(affective flattening,social withdrawal),and cognitive deficits.Its etiology reflects both strong genetic liability and environmental influences during critical stages of brain development.Dermatoglyphics,the study of epidermal ridge patterns on fingers,palms,and soles,forms between the 10th and 16th weeks of gestation,a key neurodevelopmental period.Because both the epidermis and central nervous system share an ectodermal origin,disturbances during this window may produce parallel alterations in ridge patterns and brain structure.Interest in anthropometric markers of psychiatric illness dates to the 19th century,when theories of degeneracy proposed physical anomalies as signs of hereditary vulnerability.Although controversial,dermatoglyphics has recently re-emerged as a potential non-invasive biomarker for schizophrenia.This review synthesizes evidence on dermatoglyphic patterns in schizophrenia,emphasizing twin studies,comparisons with bipolar disorder,and integration with related developmental anomalies such as minor physical anomalies and somatotype.A structured search of PubMed and Scopus(January 2004 to December 2024)identified 83 eligible studies.Inclusion criteria encompassed original human research,reviews,or meta-analyses on dermatoglyphics in schizophrenia or related psychotic disorders,while excluding animal studies,non-quantitative case reports,and non-English papers without translation.Consistent findings include reduced total ridge counts,increased fluctuating asymmetry,and greater prevalence of abnormal palmar flexion creases among individuals with schizophrenia.Twin designs show anomalies are more frequent in affected co-twins,even among monozygotic pairs,underscoring prenatal environmental effects.Comparative work suggests schizophrenia and bipolar disorder share some but not all dermatoglyphic alterations,offering potential diagnostic value.Dermatoglyphic analysis is stable,inexpensive,and non-invasive,supporting its promise as an adjunctive biomarker of neurodevelopmental disruption.However,methodological variability and limited standardization currently restrict clinical application.Future research should harmonize measurement techniques and integrate genomic and neuroimaging correlates.
基金supported by the National Key R&D Program of China(No.2018AAA0100300)the National Natural Science Foundation of China(Nos.82072018,82274375,and 82402490)+5 种基金the Anhui Provincial Science and Technology Major Project(No.202203a07020006)the Strategic Priority Research Program(C)of the Chinese Academy of Sciences(CAS)(No.XDC07040200)the Key R&D Program of Anhui Province(No.2022e07020012)the Natural Science Foundation of Anhui Province(No.2208085QH256)the Fundamental Research Funds for the Central Universities(No.WK2100000042)the China Postdoctoral Science Foundation(No.2022M713055).
文摘Neuroinflammation is the primary driver and signature of many neurodevelopmental disorders.However,because neurodevelopmental disorders caused by neuroinflammation are difficult to detect at the early stage,their progression remains unclear.To date,neither animal experiments nor in vitro models have uncovered their early developmental characteristics caused by neuroinflammation.In this study,we developed a neurovascular-unit-on-a-chip(NVU-on-a-chip)to model inflammation-induced neurodevelopmental disorders.With the chip,dynamic visualization of the progression caused by neuroinflammation was clearly demonstrated,and the changes in angiogenesis and neural differentiation under neuroinflammation were replicated.In addition,the activation of astrocytes and damage to neurons and capillaries at the early stage of neurodevelopmental disorders were observed.The results revealed for the first time the structural disruption of the neurovascular units and the neurovascular coupling failure caused by neuroinflammation.Furthermore,the outcomes of anti-inflammatory intervention using ibuprofen were preliminarily demonstrated.This work provides insights into the early progression of neurodevelopmental disorders caused by neuroinflammation and offers a platform for the development of therapeutic strategies for neuroinflammation.
基金partially supported by grants PID2020-115096RB-I00 and PID2023-148273NB-I00 from Ministerio de Ciencia y Universidad (MICIU/AEI)(to EMS)。
文摘GEMIN5 is a predominantly cytoplasmic multifunctional protein, known to be involved in recognizing snRNAs through its WD40 repeats domain placed at the N-terminus. A dimerization domain in the middle region acts as a hub for protein–protein interaction, while a non-canonical RNA-binding site is placed towards the C-terminus. The singular organization of structural domains present in GEMIN5 enables this protein to perform multiple functions through its ability to interact with distinct partners, both RNAs and proteins. This protein exerts a different role in translation regulation depending on its physiological state, such that while GEMIN5 down-regulates global RNA translation, the C-terminal half of the protein promotes translation of its mRNA. Additionally, GEMIN5 is responsible for the preferential partitioning of mRNAs into polysomes. Besides selective translation, GEMIN5 forms part of distinct ribonucleoprotein complexes, reflecting the dynamic organization of macromolecular complexes in response to internal and external signals. In accordance with its contribution to fundamental cellular processes, recent reports described clinical loss of function mutants suggesting that GEMIN5 deficiency is detrimental to cell growth and survival. Remarkably, patients carrying GEMIN5 biallelic variants suffer from neurodevelopmental delay, hypotonia, and cerebellar ataxia. Molecular analyses of individual variants, which are defective in protein dimerization, display decreased levels of ribosome association, reinforcing the involvement of the protein in translation regulation. Importantly, the number of clinical variants and the phenotypic spectrum associated with GEMIN5 disorders is increasing as the knowledge of the protein functions and the pathways linked to its activity augments. Here we discuss relevant advances concerning the functional and structural features of GEMIN5 and its separate domains in RNA-binding, protein interactome, and translation regulation, and how these data can help to understand the involvement of protein malfunction in clinical variants found in patients developing neurodevelopmental disorders.
文摘Mitochondrial dysfunction has emerged as a critical factor in the etiology of various neurodevelopmental disorders, including autism spectrum disorders, attention-deficit/hyperactivity disorder, and Rett syndrome. Although these conditions differ in clinical presentation, they share fundamental pathological features that may stem from abnormal mitochondrial dynamics and impaired autophagic clearance, which contribute to redox imbalance and oxidative stress in neurons. This review aimed to elucidate the relationship between mitochondrial dynamics dysfunction and neurodevelopmental disorders. Mitochondria are highly dynamic organelles that undergo continuous fusion and fission to meet the substantial energy demands of neural cells. Dysregulation of these processes, as observed in certain neurodevelopmental disorders, causes accumulation of damaged mitochondria, exacerbating oxidative damage and impairing neuronal function. The phosphatase and tensin homolog-induced putative kinase 1/E3 ubiquitin-protein ligase pathway is crucial for mitophagy, the process of selectively removing malfunctioning mitochondria. Mutations in genes encoding mitochondrial fusion proteins have been identified in autism spectrum disorders, linking disruptions in the fusion-fission equilibrium to neurodevelopmental impairments. Additionally, animal models of Rett syndrome have shown pronounced defects in mitophagy, reinforcing the notion that mitochondrial quality control is indispensable for neuronal health. Clinical studies have highlighted the importance of mitochondrial disturbances in neurodevelopmental disorders. In autism spectrum disorders, elevated oxidative stress markers and mitochondrial DNA deletions indicate compromised mitochondrial function. Attention-deficit/hyperactivity disorder has also been associated with cognitive deficits linked to mitochondrial dysfunction and oxidative stress. Moreover, induced pluripotent stem cell models derived from patients with Rett syndrome have shown impaired mitochondrial dynamics and heightened vulnerability to oxidative injury, suggesting the role of defective mitochondrial homeostasis in these disorders. From a translational standpoint, multiple therapeutic approaches targeting mitochondrial pathways show promise. Interventions aimed at preserving normal fusion-fission cycles or enhancing mitophagy can reduce oxidative damage by limiting the accumulation of defective mitochondria. Pharmacological modulation of mitochondrial permeability and upregulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, an essential regulator of mitochondrial biogenesis, may also ameliorate cellular energy deficits. Identifying early biomarkers of mitochondrial impairment is crucial for precision medicine, since it can help clinicians tailor interventions to individual patient profiles and improve prognoses. Furthermore, integrating mitochondria-focused strategies with established therapies, such as antioxidants or behavioral interventions, may enhance treatment efficacy and yield better clinical outcomes. Leveraging these pathways could open avenues for regenerative strategies, given the influence of mitochondria on neuronal repair and plasticity. In conclusion, this review indicates mitochondrial homeostasis as a unifying therapeutic axis within neurodevelopmental pathophysiology. Disruptions in mitochondrial dynamics and autophagic clearance converge on oxidative stress, and researchers should prioritize validating these interventions in clinical settings to advance precision medicine and enhance outcomes for individuals affected by neurodevelopmental disorders.
基金supported by grants from the National Natural Science Foundation of China(32130043 to X.Z.)the Scientific&Technological Innovation(STI)2030-Major Project(2022ZD0204900 to X.Z.)+1 种基金the National Natural Science Foundation of China(32400870 to Z.S.)the Fundamental Research Funds for the Central Universities(2243300002 to Z.S.).
文摘Critical periods(CPs)are defined as postnatal developmental windows during which brain circuits exhibit heightened sensitivity to altered experiences or sensory inputs,particularly during brain development in humans and animals.During the CP,experience-induced refinements of neural connections are crucial for establishing adaptive and mature brain functions,and aberrant CPs are often accompanied by many neurodevelopmental disorders(NDDs),including autism spectrum disorders and schizophrenia.Understanding neural mechanisms underlying the CP regulation is key to delineating the etiology of NDDs caused by abnormal postnatal neurodevelopment.Recent evidence from studies using innovative experimental tools has continuously revisited the inhibition-gating theory of CP to systematically elucidate the differential roles of distinct inhibitory circuits.Here,we provide a comprehensive review of classical experimental findings and emerging inhibitory-circuit regulation mechanisms of the CP,and further discuss how aberrant CP plasticity is associated with NDDs.
基金supported by the National Natural Science Foundation of China[81701350 and 31671252]the Health Technology Plan of Zhejiang Province[2023RC205].
文摘Maternal health during pregnancy has a direct impact on the risk and severity of neurodevelopmental disorders(NDDs)in the offspring,especially in the case of drug exposure.However,little progress has been made to assess the risk of drug exposure during pregnancy due to ethical constraints and drug use factors.We collected and manually curated sub-pathways and pathways(sub-/pathways)and drug information to propose an analytical framework for predicting drug candidates.This framework linked sub-/pathway activity and drug response scores derived from gene transcription data and was applied to human fetal brain development and six NDDs.Further,specific and pleiotropic sub-/pathways/drugs were identified using entropy,and sex bias was analyzed in conjunction with logistic regression and random forest models.We identified 19 disorder-associated and 256 regionally pleiotropic and specific candidate drugs that targeted risk sub-/pathways in NDDs,showing temporal or spatial changes across fetal development.Moreover,5443 differential drug-sub-/pathways exhibited sex-biased differences after filling in the gender labels.A user-friendly NDDP visualization website(https://ndd-lab.shinyapps.io/NDDP)was developed to allow researchers and clinicians to access and retrieve data easily.Our framework overcame data gaps and identified numerous pleiotropic and specific candidates across six disorders and fetal developmental trajectories.This could significantly contribute to drug discovery during pregnancy and can be applied to a wide range of traits.
文摘BACKGROUND Neurodevelopmental delays encompass a wide range of conditions that impair cognitive,motor,and social functioning,often increasing the risk of psychiatric comorbidities.Children with these delays frequently present with disorders such as attention-deficit/hyperactivity disorder(ADHD),anxiety,and behavioral disturbances,which can significantly affect development and quality of life.While genetic predisposition has been linked to these comorbidities,growing evidence highlights the role of environmental factors,including prenatal and early-life stressors.However,the interaction between genetic susceptibility and environmental influences remains poorly understood.Identifying specific genetic variants,environmental risks,and their interactions is essential for early detection and targeted interventions.AIM To investigate the combined effects of genetic and environmental factors on psychiatric comorbidities in children with neurodevelopmental delays,elucidate underlying mechanisms,and inform clinical management strategies.METHODS This retrospective cohort study included 80 children with confirmed neurodevelopmental delays and 40 age-and sex-matched typically developing controls.Comprehensive clinical and psychiatric evaluations,genetic testing(chromosomal microarray analysis and targeted next-generation sequencing),and environmental exposure assessments were conducted.Statistical analyses explored associations between genetic variants and psychiatric comorbidities,environmental risk factors,and gene-environment interactions.RESULTS Children with neurodevelopmental delays exhibited significantly higher rates of psychiatric comorbidities(70.0%)compared to controls(15.0%),with ADHD(42.5%),anxiety disorders(28.8%),and behavioral disorders(23.8%)being the most common.Pathogenic genetic variants were identified in specific pathways associated with distinct psychiatric presentations:Glutamatergic signaling variants were linked to anxiety disorders(odds ratio=3.8),dopaminergic system variants to ADHD(odds ratio=4.2),and synaptic function variants to both behavioral and anxiety disorders.Environmental factors,particularly prenatal maternal stress,early childhood adversity,and family dysfunction were strong predictors of psychiatric outcomes(β=0.42).Significant gene-environment interactions were identified,indicating that environmental exposure can moderate the effects of genetic risks on psychiatric outcomes.CONCLUSION Psychiatric comorbidities in children with neurodevelopmental delays are significantly influenced by both genetic and environmental factors,with complex interactions between the two.These findings underscore the need for integrated assessments and targeted interventions addressing both biological and environmental contributors to improve outcomes in this vulnerable population.
基金supported by grants from the National Key Research and Development Program of China(2022YFA1303900 and 2021YFC2700705)the National Natural Science Foundation of China(82103919).
文摘The impact of mother-infant microbiota on neurodevelopment is an area of interest,but longitudinal studies are scarce.Using a cohort of 520 families from the Jiangsu birth cohort in China,we reveal that the maternal gut microbiota during early pregnancy play a substantial role,accounting for 3.34%of the variance in offspring neurodevelopmental scores.This contribution is notably higher than the 1.24%attributed to the infants’own microbiota at 1 year of age,underscoring the significant influence of maternal gut health on early child development.Remarkably,an elevation in maternal Bifidobacterium pseudocatenulatum is linked to decreased cognitive scores,whereas an enrichment of Bifidobacterium longum at 1 year of age is associated with higher cognitive scores.Furthermore,we find that maternal B.pseudocatenulatum is linked to the heterolactic fermentation metabolic pathway,while infant B.longum is associated with the Bifidobacterium shunt pathway.In summary,our analysis implies that maternal and infant gut microbiota play a distinct role in neurodevelopment,suggesting potential strategies for improving neurodevelopmental outcomes during early pregnancy or infant development by targeting gut microbiota composition.
基金supported by the National Natural Science Foundation of China(82270310)Noncommunicable Chronic Diseases-National Science and Technology Major Project(No.2024ZD0527000 and No.2024ZD0527005)+2 种基金Jiangsu Provincial key research and development program(BE2023662)General project of Nanjing Health Commission(YKK22166).
文摘Background:The life-course management of children with tetralogy of Fallot(TOF)has focused on demonstrating brain structural alterations,developmental trajectories,and cognition-related changes that unfold over time.Methods:We introduce an magnetic resonance imaging(MRI)dataset comprising TOF children who underwent brain MRI scanning and cross-sectional neurocognitive follow-up.The dataset includes brain three-dimensional T1-weighted imaging(3D-T1WI),three-dimensional T2-weighted imaging(3D-T2WI),and neurodevelopmental evaluations using the Wechsler Preschool and Primary Scale of Intelligence–Fourth Edition(WPPSI-IV).Results:Thirty-one children with TOF(age range:4–33 months;18 males)were recruited and completed corrective surgery at the Children’s Hospital of Nanjing Medical University,Nanjing,China.Aiming to promote the neurodevelopmental outcomes in children with TOF,we have meticulously curated a comprehensive dataset designed to dissect the complex interplay among risk factors,neuroimaging findings,and adverse neurodevelopmental outcomes.Conclusion:This article aims to introduce our open-source dataset on neurodevelopment in children with TOF,which covers the data types,data acquisition and processing methods,the procedure for accessing the data,and related publications.
文摘Background: Spinal dysraphism represents a wide spectrum of congenital abnormalities of the spine. Myelomeningocele is considered the most common malformation and the most common we saw in our community, with its morbidity problems seen commonly in the postoperative period. ASQ-3<sup>TM</sup> Scores are the ages and stages questionnaire, third edition, and represent a tool to assess the development progress, especially in toddlers. Objectives: Evaluation of neurodevelopmental outcome among Sudanese toddlers with spinal dysraphism after surgical closure with or without a VP shunt using ASQ-3<sup>TM</sup> Scores. Methodology: This is a retrospective hospital-based study of 84 patients who underwent myelomeningocele repair at the National Center for Neurological Sciences (NCNS) during the period from 2017 up to 2019. Data were collected through a constructed questionnaire, including ASQ-3<sup>TM</sup> Scores. Data were processed and analyzed using the Statistical Package for Social Science (SPSS) computer program. Version 25. Results: 84 patients were included in this study;all patients were diagnosed with spinal dysraphism. Out of them, 51 (60.7%) were 2 years old, 33 (39.3%) were 3 years old, 45 (53.6%) were male, 45 (53.6%) of patients mothers attended ANC irregularly, and 54 (64.3%) their mothers didn’t receive folate supplements. 44 (52.3%) of patients underwent MMC repair only, while 40 (47.7%) underwent MMC repair and VP shunt. The commonest postoperative complication was infection, reported in 12 (14.3%) of patients, followed by VP shunt revision in 9 (10.7%) of patients. Neurological assessment showed that the majority of patients need further assessment with a professional, 57 (67.9%) of children don’t walk, run, or climb like other toddlers as their parent’s state;also, half of patients (42, 50%) had medical problems, and 27 (32.1%) of their parent’s state that they do not talk like other toddlers their age. There was a statistically significant association between post-operative complications and communication development, problem-solving development, and personal social development (P value = 0.05), and a statistically significant association was found between age at repair and neurological development (P value = 0.05). Conclusion: The majority of patients had motor deficiency (particularly gross motor) and poor personal and social skills. Age at repair and postoperative complications significantly influenced the neurological development.
基金supported by the U.S.National Institutes of Health(NIH)National Institute of Neurological Disorders and Stroke(NINDS),No.R01 NS134215(to UBP).
文摘The recent identification of a neurodevelopmental disorder with cerebellar atrophy and motor dysfunction(NEDCAM)has resulted in an increased interest in GEMIN5,a multifunction RNA-binding protein.As the largest member of the survival motor neuron complex,GEMIN5 plays a key role in the biogenesis of small nuclear ribonucleoproteins while also exhibiting translational regulatory functions as an independent protein.Although many questions remain regarding both the pathogenesis and pathophysiology of this new disorder,considerable progress has been made in the brief time since its discovery.In this review,we examine GEMIN5 within the context of NEDCAM,focusing on the structure,function,and expression of the protein specifically in regard to the disorder itself.Additionally,we explore the current animal models of NEDCAM,as well as potential molecular pathways for treatment and future directions of study.This review provides a comprehensive overview of recent advances in our understanding of this unique member of the survival motor neuron complex.
文摘Objective: This study aimed to assess perinatal morbidity, mortality rates, and neurodevelopmental outcomes in the management of fetal growth restriction (FGR) at a single tertiary institute. Methods: Among 2465 deliveries between 2013 and 2019, 109 cases of FGR were reviewed retrospectively for causes, indications for pregnancy termination, perinatal death, overall neonatal outcomes, and long-term prognosis. Results: Excluding FGR due to congenital anomalies (n = 17), the mortality rate was 3.3% (3/92). One neonate delivered at 23 weeks developed cerebral palsy (1.1%). Retinopathy of prematurity occurred in four neonates (4.3%). Neurodevelopmental disorders were present in six neonates (6.5%), all of whom were delivered at 32 - 38 weeks. Significantly lower gestational age at delivery, lower birth weight, and higher umbilical artery resistance indices were observed in neonates with neurodevelopmental disorders. Conclusions: Intact survival before 27 weeks of gestation at delivery with FGR is uncommon. Neurodevelopmental disorders may still develop after delivery at 32 - 38 weeks;consideration should be given to the timing of delivery usingfetal ductus venosus Doppler waveforms measurements to reduce neurodevelopmental disorders.
基金supported by the National Natural Science Foundation of China (Nos.32071301,31971234 and 42177411)the Natural Science Foundation of Fujian Province,China (No.2020J01027)。
文摘Tributyltin(TBT),a common organotin environmental pollutant,may pose a threat to human development during critical early-life periods.We aimed to assess the neurodevelopmental intergenerational toxicity of early-life exposure to TBT and the protective effect of DNA methyl donor folic acid(FA).Specifically,after early-life exposure(1–21 days postfertilization,dpf)to TBT(0,1,10 and 100 ng/L),zebrafish(Danio rerio)were cultured in clean medium until sexual maturity.The exposed females were mated with unexposed males to produce embryos(F1).The F1 generation were cultured(4–120 hours post-fertilization,hpf)with and without 1 mmol/L FA.The neurotoxic effects of early-life TBT exposure for zebrafish and their offspring(F1)were significantly enhanced anxiety and reduced aggression,decreased gene expression of DNA methyltransferase in the brain and increased serotonin levels in the body.Moreover,the intergenerational neurodevelopmental toxicity,as manifested in the F1 generation,was attenuated by FA supplementation.In summary,early-life TBT exposure led to intergenerational neurodevelopmental deficits in zebrafish,and DNA methyl donors had a protective effect on F1 neurodevelopment,which can inform the prevention and treatment of intergenerational neurotoxicity due to organotin pollutants.
文摘Neurodevelopmental disorders are characterized by an abnormal development of the central nervous system, leading to a myriad of symptoms and diseases, including intellectual disability, attention deficits, impairments in learning and memory, speech disorders and repetitive behavior （Telias and Ben-Yosef, 2014）. Common major neurodevelopmental disorders include autism and autism spectrum disorders （ASDs）, fragile X syndrome （FXS）, Down syndrome （DS）, and Rett syndrome （RTT）. They can be collectively described as disorders in which the plasticity of the brain has been severely impaired. The concept of plasticity refers to the brain＇s ability to adapt to and process new information and react accordingly, and it can be classified into three categories： a） molecular plasticity, whenever specific receptors, ion channels, enzymes,
基金supported by the National Natural Science Foundation of China(81871079,81730036,82130043)the National Brain Science and Brain-like Research of China(2021ZD0201704)+2 种基金the National Key Research and Development Program of China(2021YFA0805200)the Hunan Provincial grands(2021JJ10070,2019SK1015,2019RS2005,2019SK1010,B2019138)the High Performance Computing Center of Central South University。
文摘Autism spectrum disorder(ASD)is a group of neurodevelopmental disorders that cause severe social,communication,and behavioral problems.Recent studies show that the variants of a histone methyltransferase gene KMT5B cause neurodevelopmental disorders(NDDs),including ASD,and the knockout of Kmt5b in mice is embryonic lethal.However,the detailed genotype-phenotype correlations and functional effects of KMT5B in neurodevelopment are unclear.By targeted sequencing of a large Chinese ASD cohort,analyzing published genome-wide sequencing data,and mining literature,we curated 39 KMT5B variants identified from NDD individuals.A genotype-phenotype correlation analysis for 10 individuals with KMT5B pathogenic variants reveals common symptoms,including ASD,intellectual disability,languages problem,and macrocephaly.In vitro knockdown of the expression of Kmt5b in cultured mouse primary cortical neurons leads to a decrease in neuronal dendritic complexity and an increase in dendritic spine density,which can be rescued by expression of human KMT5B but not that of pathogenic de novo missense mutants.In vivo knockdown of the Kmt5b expression in the mouse embryonic cerebral cortex by in utero electroporation results in decreased proliferation and accelerated migration of neural progenitor cells.Our findings reveal essential roles of histone methyltransferase KMT5B in neuronal development,prenatal neurogenesis,and neuronal migration.
基金the Heinrich and Alma Vogelsang Foundation for financial support in the form of a graduation scholarship
文摘Vascular endothelial growth factor（VEGF）in neurodevelopment and regeneration：VEGF is a well-known factor that promotes vascularization and angiogenesis.Besides this it participates in the pathogenesis of several diseases,such as colorectal carcinoma,lung cancer or diabetic retinopathy.Within the last decade,VEGF has been successfully integrated into the treatment of such diseases,for example as a therapy for colorectal cancer with the VEGF-receptor （VEGFR）-inhibitor axitinib.
基金supported by Research Grant from the University of Brescia(to Memo M).
文摘Mice use ultrasonic vocalizations(USVs)to communicate each other and to convey their emotional state.USVs have been greatly characterized in specific life phases and contexts,such as mother isolation-induced USVs for pups or female-induced USVs for male mice during courtship.USVs can be acquired by means of specific tools and later analyzed on the base of both quantitative and qualitative parameters.Indeed,different ultrasonic call categories exist and have already been defined.The understanding of different calls meaning is still missing,and it will represent an essential step forward in the field of USVs.They have long been studied in the ethological context,but recently they emerged as a precious instrument to study pathologies characterized by deficits in communication,in particular neurodevelopmental disorders(NDDs),such as autism spectrum disorders.This review covers the topics of USVs characteristics in mice,contexts for USVs emission and factors that modulate their expression.A particular focus will be devoted to mouse USVs in the context of NDDs.Indeed,several NDDs murine models exist and an intense study of USVs is currently in progress,with the aim of both performing an early diagnosis and to find a pharmacological/behavioral intervention to improve patients’quality of life.
