The mechanistic target of rapamycin(m TOR) is a serine/threonine kinase that plays a pivotal role in cellular growth, proliferation, survival, and metabolism. In the central nervous system(CNS), the mTOR pathway regul...The mechanistic target of rapamycin(m TOR) is a serine/threonine kinase that plays a pivotal role in cellular growth, proliferation, survival, and metabolism. In the central nervous system(CNS), the mTOR pathway regulates diverse aspects of neural development and function. Genetic mutations within the m TOR pathway lead to severe neurodevelopmental disorders, collectively known as “mTORopathies”(Crino, 2020). Dysfunctions of m TOR, including both its hyperactivation and hypoactivation, have also been implicated in a wide spectrum of other neurodevelopmental and neurodegenerative conditions, highlighting its importance in CNS health.展开更多
The nervous system is a complex network with many types of neurons and numerous synaptic connections.The present knowledge on how neurons recognize specific targets and form such an intricate network is still limited....The nervous system is a complex network with many types of neurons and numerous synaptic connections.The present knowledge on how neurons recognize specific targets and form such an intricate network is still limited.The Down syndrome cell adhesion molecule （DSCAM） belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients.DSCAM plays important roles in neural development,including dendritic patterning and self-avoidance,axon guidance and branching,axon target recognition and synaptic formation.However,the functional mechanisms and the underlying signaling pathways are still largely unknown.Here the functions of DSCAM in neural development were reviewed.Future research for better understanding DSCAM function and the relevance of DSCAM to human diseases was also discussed.展开更多
Receptor for activated C kinase 1（RACK1）is an evolutionarily conserved scaffolding protein within the tryptophan-aspartate（WD）repeat family of proteins.RACK1 can bind multiple signaling molecules concurrently,as w...Receptor for activated C kinase 1（RACK1）is an evolutionarily conserved scaffolding protein within the tryptophan-aspartate（WD）repeat family of proteins.RACK1 can bind multiple signaling molecules concurrently,as well as stabilize and anchor proteins.RACK1 also plays an important role at focal adhesions,where it acts to regulate cell migration.In addition,RACK1 is a ribosomal binding protein and thus,regulates translation.Despite these numerous functions,little is known about how RACK1 regulates nervous system development.Here,we review three studies that examine the role of RACK1 in neural development.In brief,these papers demonstrate that（1）RACK-1,the C.elegans homolog of mammalian RACK1,is required for axon guidance;（2）RACK1 is required for neurite extension of neuronally differentiated rat PC12cells;and（3）RACK1 is required for axon outgrowth of primary mouse cortical neurons.Thus,it is evident that RACK1 is critical for appropriate neural development in a wide range of species,and future discoveries could reveal whether RACK1 and its signaling partners are potential targets for treatment of neurodevelopmental disorders or a therapeutic approach for axonal regeneration.展开更多
SRY-related HMG-box(Sox) transcription factors are known to regulate central nervous system development and are involved in several neurological diseases.Post-translational modification of Sox proteins is known to alt...SRY-related HMG-box(Sox) transcription factors are known to regulate central nervous system development and are involved in several neurological diseases.Post-translational modification of Sox proteins is known to alter their functions in the central nervous system.Among the different types of post-translational modification,small ubiquitin-like modifier(SUMO) modification of Sox proteins has been shown to modify their transcriptional activity.Here,we review the mechanisms of three Sox proteins in neuronal development and disease,along with their transcriptional changes under SUMOylation.Across three species,lysine is the conserved residue for SUMOylation.In Drosophila,SUMOylation of Sox N plays a repressive role in transcriptional activity,which impairs central nervous system development.However,de SUMOylation of Sox E and Sox11 plays neuroprotective roles,which promote neural crest precursor formation in Xenopus and retinal ganglion cell differentiation as well as axon regeneration in the rodent.We further discuss a potential translational therapy by SUMO site modification using AAV gene transduction and Clustered regularly interspaced short palindromic repeats-Cas9 technology.Understanding the underlying mechanisms of Sox SUMOylation,especially in the rodent system,may provide a therapeutic strategy to address issues associated with neuronal development and neurodegeneration.展开更多
BACKGROUND： Exposure to low-level lead has a toxic effect on the development of neonates, which has attracted wide attention. Colostrum lead level can be used as the indication of lead exposure. OBJECTIVE： To observ...BACKGROUND： Exposure to low-level lead has a toxic effect on the development of neonates, which has attracted wide attention. Colostrum lead level can be used as the indication of lead exposure. OBJECTIVE： To observe the relationship of colostrum lead level and the neurobehavioral development of infants. DESIGN： A prospective control observation. SETTING： Center for Maternal and Child Health, Shanxi Provincial Children＇s Hospital. PARTICIPANTS： Totally 128 neonates of full-term normal delivery, 76 male and 52 female, from Shanxi Provincial Maternal and Child Health Center and Jiexiu Maternal and Child Health Center were involved in this study. All the involved neonates had no peripartal ischemic/hypoxic history or fetus intrauterine developmental lag. Pregnant women had no various acute and chronic diseases in pregnancy, family history of neurological disease or occupational lead exposure. 128 portions of colostrum sample of full-term normal delivery were collected. Informed consents of detected items were obtained from the puerperants and their relatives. METHODS： ① Experimental grouping： Lead level in the colostrum was determined by atomic absorption spectrometry. According to lead level in the colostrum, the neonates were classified into two exposure groups of greater than or equal to 0.24 μmol/L in a high-level lead group and less than 0.24 μ mol/L in a low-level lead group. ② Experimental evaluation： Mental developmental index （MDI） and psychological developmental index （PDI） of 3-month-old infants were evaluated with Bayley Scales of Infant Development （BSID）. The relationships of MDI, PDI and colostrum lead level were performed correlation regression analysis; The relationship of colostrum lead level and development was performed multi-factor analysis with family environment and health questionnaires. MAIN OUTCOME MEASURES： ① Evaluation results of MDI and PDI. ② Multi-factor analysis results. RESULTS： Totally 128 neonates were involved in the study. Ten and eleven neonates were lost due to emigration in the high-level lead group and low-level lead group respectively, and the other 107 neonates participated in the final analysis. ① MDI and PDI in the high-level lead group were significantly lower than those in the low-level lead group, respectively （P 〈 0.01）; Regression analysis results showed that two developmental indexes were statistically negatively correlated with colostrum lead level （regression equation y = 1.9＋0.01x1,-0.04x2,＋0.04x3,＋0.03x4）. ② Four variables of the factors included by family environment and health questionnaires were taken into equation. Large maternal age, irrational dietary pattern in pregnancy and pollution degree of habitation environment in pregnancy were the risk factors of colostrum lead level （partial regression coefficien t =0.598 4,0.426 8,0.306 7,P 〈 0.05-0.01）, and calcium supplementation in pregnancy was a protective factor （partial regression coefficien t =-0.455 8, P 〈 0.01）. CONCLUSION： High colostrum lead level will have adverse effects on the early development of neonates; Large maternal age, irrational dietary pattern in pregnancy and pollution degree of habitation environment in pregnancy are the risk factors of colostrum lead level, and calcium supplementation in pregnancy was a protective factor.展开更多
flamingo is among the ＇core＇ planar cell-polarity genes, protein of which belongs to a unique cadherin subfamily. In contrast to the classic cadherins, composed of several extracellular cadherin repeats, one transme...flamingo is among the ＇core＇ planar cell-polarity genes, protein of which belongs to a unique cadherin subfamily. In contrast to the classic cadherins, composed of several extracellular cadherin repeats, one transmembrane domain and one cytoplasmic segment linked to catenin binding, Drosophila Flamingo has seven transmembrane segments and a cytoplasmic tail with no catenin-binding sequence. In Drosophila, Flamingo has pleotropic roles in controlling epithelial polarity and neuronal morphogenesis. Three mammalian orthologs of flamingo, Celsrl-3, are widely expressed in the nervous system. Recent work has shown that Celsrl-3 play important roles in neural development, such as in axon guidance, neuronal migration, and cilium polarity. CeIsrl-3 single-gene knockout mice exhibit different phenotypes, but there are cooperative interactions among these genes.展开更多
The matrix metalloproteinases（MMPs） are a family of zinc-dependent endopeptidases originally characterized as secreted proteases responsible for degrading extracellular matrix proteins.Their canonical role in matrix...The matrix metalloproteinases（MMPs） are a family of zinc-dependent endopeptidases originally characterized as secreted proteases responsible for degrading extracellular matrix proteins.Their canonical role in matrix remodelling is of significant importance in neural development and regeneration,but emerging roles for MMPs,especially in signal transduction pathways,are also of obvious importance in a neural context.Misregulation of MMP activity is a hallmark of many neuropathologies,and members of every branch of the MMP family have been implicated in aspects of neural development and disease.However,while extraordinary research efforts have been made to elucidate the molecular mechanisms involving MMPs,methodological constraints and complexities of the research models have impeded progress.Here we discuss the current state of our understanding of the roles of MMPs in neural development using recent examples and advocate a phylogenetically diverse approach to MMP research as a means to both circumvent the challenges associated with specific model organisms,and to provide a broader evolutionary context from which to synthesize an understanding of the underlying biology.展开更多
Xenopus ZFP36L1(zinc finger protein 36,C3H type-like 1)belongs to the ZFP36 family of RNA-binding proteins,which contains two characteristic tandem CCCH-type zinc-finger domains.The ZFP36 proteins can bind AU-rich ele...Xenopus ZFP36L1(zinc finger protein 36,C3H type-like 1)belongs to the ZFP36 family of RNA-binding proteins,which contains two characteristic tandem CCCH-type zinc-finger domains.The ZFP36 proteins can bind AU-rich elements in 3'untranslated regions of target mRNAs and promote their turnover.However,the expression and role of ZFP36 genes during neural development in Xenopus embryos remains largely unknown.The present study showed that Xenopus ZFP36L1 was expressed at the dorsal part of the forebrain,forebrain-midbrain boundary,and midbrain-hindbrain boundary from late neurula stages to tadpole stages of embryonic development.Overexpression of XZFP36L1 in Xenopus embryos inhibited neural induction and differentiation,leading to severe neural tube defects.The function of XZP36L1 requires both its zinc finger and C terminal domains,which also affect its subcellular localization.These results suggest that XZFP36L1 is likely involved in neural development in Xenopus and might play an important role in post-transcriptional regulation.展开更多
Xenopus ZFP36L1 （zinc finger protein 36, C3H type-like 1） belongs to the ZFP36 family of RNA-binding proteins, which contains two characteristic tandem CCCH-type zinc-finger domains. The ZFP36 proteins can bind AU-r...Xenopus ZFP36L1 （zinc finger protein 36, C3H type-like 1） belongs to the ZFP36 family of RNA-binding proteins, which contains two characteristic tandem CCCH-type zinc-finger domains. The ZFP36 proteins can bind AU-rich elements in 3＇ untranslated regions of target mRNAs and promote their turnover. However, the expression and role of ZFP36 genes during neural development in Xenopus embryos remains largely unknown. The present study showed that Xenopus ZFP36L1 was expressed at the dorsal part of the forebrain, forebrain-midbrain boundary, and midbrain-hindbrain boundary from late neurula stages to tadpole stages of embryonic development. Overexpression of XZFP36L1 in Xenopus embryos inhibited neural induction and differentiation, leading to severe neural tube defects. The function of XZP36L1 requires both its zinc finger and C terminal domains, which also affect its subcellular localization. These results suggest that XZFP36L1 is likely involved in neural development in Xenopus and might play an important role in post-transcriptional regulation.展开更多
Different fates of neural stem/progenitor cells(NSPCs)and their progeny are determined by the gene regulatory network,where a chromatin-remodeling complex affects synergy with other regulators.Here,we review recent re...Different fates of neural stem/progenitor cells(NSPCs)and their progeny are determined by the gene regulatory network,where a chromatin-remodeling complex affects synergy with other regulators.Here,we review recent research progress indicating that the BRG1/BRM-associated factor(BAF)complex plays an important role in NSPCs during neural development and neural developmental disorders.Several studies based on animal models have shown that mutations in the BAF complex may cause abnormal neural differentiation,which can also lead to various diseases in humans.We discussed BAF complex subunits and their main characteristics in NSPCs.With advances in studies of human pluripotent stem cells and the feasibility of driving their differentiation into NSPCs,we can now investigate the role of the BAF complex in regulating the balance between self-renewal and differentiation of NSPCs.Considering recent progress in these research areas,we suggest that three approaches should be used in investigations in the near future.Sequencing of whole human exome and genome-wide association studies suggest that mutations in the subunits of the BAF complex are related to neurodevelopmental disorders.More insight into the mechanism of BAF complex regulation in NSPCs during neural cell fate decisions and neurodevelopment may help in exploiting new methods for clinical applications.展开更多
Basic helix-loop-helix （bHLH） transcription factors regulate the differentiation of various tissues in a vast diversity of species. The bHLH protein Atonal was first identified as a proneural gene involved in the fo...Basic helix-loop-helix （bHLH） transcription factors regulate the differentiation of various tissues in a vast diversity of species. The bHLH protein Atonal was first identified as a proneural gene involved in the formation of mechanosensory cells and photoreceptor cells in Drosophila （larman et al., 1993, 1994）. Atonal is expressed in sensory organ precursors and is required and sufficient for the development of chordotonal organs （Jar- man et al., 1993）. Moreover, Atonal expression is observed in the developing eye and is essential for the differentiation of R8 photoreceptors, which are the first photoreceptors that appear during development. Atonal is not involved in the formation of other photoreceptors （R1-R7） directly. However, R8 photore- ceptors recruit other photoreceptors from the surrounding cells （Jarman et al., 1994）.展开更多
Objective:To explore the combined effects of multisensory intervention and amplitude integrated electroencephalogram monitoring on the maturation and evaluation of brain and neural development in premature infants of ...Objective:To explore the combined effects of multisensory intervention and amplitude integrated electroencephalogram monitoring on the maturation and evaluation of brain and neural development in premature infants of different gestational ages.Methods:The controlled trial was carried out in 62 premature infants from January to February of 2023 in Genertec AMHT-Baogang Hospital.The premature infants were divided into two groups according to the gestational age:32-33^(+6W)(Group A)and 34-36^(+6W)(Group B).By use of random number table method,each group was subdivided into the control group and the experimental group.The control group was monitored with aEEG within 1 day and the following 7 days after birth.The experimental group was monitored with aEEG within 1 day and the following 7 days after multisensory intervention(MS)to observe the change of aEEG parameters,in order to explore the effect of MS intervention on brain development maturity.The Neonatal Behavioral Neurological Assessment(NBNA)score was performed at 40 weeks of corrected gestational age in both groups.Results:The amplitude voltage,the total aEEG score and the sleep-wake cycle score in the experimental group were higher than those in the control group(p<.05).The total NBNA score in the experimental group was higher than that in the control group.Conclusions:The multi-sensory intervention is a simple and feasible method of development support nursing,it can improve the total NBNA score of premature infants,which can promote the brain development in premature infants and improve their neurodevelopmental behavior.展开更多
There are few studies on the membrane protein Ankfyl. We have found Ankfyl is specifically expressed in neural stem/precursor cells during early development in mice （murine）. To further explore Ankfyl function in ne...There are few studies on the membrane protein Ankfyl. We have found Ankfyl is specifically expressed in neural stem/precursor cells during early development in mice （murine）. To further explore Ankfyl function in neural development, we developed a gene knockout mouse with a mixed Balb/C and C57/BL6 genetic background. Using immunofluorescence and in situ hybridization, neural defects were absent in mixed genetic Ankfyl null mice during development and in adults up to 2 months old. However, Ankfyl gene knockout mice with a pure genetic background were found to be lethal in the C57/BL6 inbred mice embryos, even after seven generations of backcrossing. Polymerase chain reaction confirmed homozygotes were unattainable as early as embryonic day 11.5. We conclude that Ankfyl protein is dispensable in neural stem/precursor ceils, but could be critical for early embryonic murine development, depending on the genetic background.展开更多
Neural tube development comprises neural induction, neural epithelial cell proliferation, and apoptosis, as well as migration of nerve cells. Too much or too little apoptosis leads to abnormal nervous system developme...Neural tube development comprises neural induction, neural epithelial cell proliferation, and apoptosis, as well as migration of nerve cells. Too much or too little apoptosis leads to abnormal nervous system development. The present study analyzed expression and distribution of apoptotic-related factors, including Fas, FasL, and caspase-3, during human embryonic neural tube development. Experimental results showed that increased caspase-3 expression promoted neural apoptosis via a mitochondrial-mediated intrinsic pathway at 4 weeks during early human embryonic neural tube development. Subsequently, Fas and FasL expression increased during embryonic development. The results suggest that neural cells influence neural apoptosis through synergistic effects of extrinsic pathways. Therefore, neural apoptosis during the early period of neural tube development in the human embryo might be regulated by the death receptor induced apoptotic extrinsic pathways.展开更多
The mitogen-activated protein kinase（MAPK）pathways are a group of conserved intracellular signalling pathways present in most cells including neurons and glia.These pathways respond to a variety of stimuli including...The mitogen-activated protein kinase（MAPK）pathways are a group of conserved intracellular signalling pathways present in most cells including neurons and glia.These pathways respond to a variety of stimuli including growth factors,cytokines and oxidative stress to generate appropriate cellular responses such as modulation of gene expression,cell proliferation,differentiation and survival as well as the stress response（Korhonen and Moilanen,2014）.展开更多
A major basic research projectin the field of neurosciencewas launched on November26 last year at the Shanghai-basedInstitute of Neuroscience of the Chi-nese Academy of Sciences(CAS).
High-risk infants,from fetal stage to 3-year-old,face severe physical and mental development threats due to biological,psychological,or environmental factors.These threats can lead to developmental delay and cognitive...High-risk infants,from fetal stage to 3-year-old,face severe physical and mental development threats due to biological,psychological,or environmental factors.These threats can lead to developmental delay and cognitive impairment,affecting their future quality of life and social integration.Scientific health management,with nutritional intervention as a key part,is urgently needed.Nutritional intervention,through targeted supplementation and feeding guidance,can optimize their development,avoid nutritional-related deviations,reduce long-term disease risk,and lay a healthy growth foundation.This study analyzes the positive effects of nutritional intervention on high-risk infants’physical growth,neural development,and disease prevention,providing scientific evidence for optimizing clinical follow-up strategies.展开更多
Long noncoding RNAs(lnc RNAs) are RNA molecules comprising more than 200 nucleotides, which are not translated into proteins. Many studies have shown that lnc RNAs are involved in regulating a variety of biological pr...Long noncoding RNAs(lnc RNAs) are RNA molecules comprising more than 200 nucleotides, which are not translated into proteins. Many studies have shown that lnc RNAs are involved in regulating a variety of biological processes, including immune, cancer, stress, development and differentiation at the transcriptional, epigenetic or post-transcriptional levels. Here, we review the role of lnc RNAs in the process of neurodevelopment, neural differentiation, synaptic function, and pathogenesis of Parkinson’s disease(PD). These pathomechanisms include protein misfolding and aggregation, disordered protein degradation, mitochondrial dysfunction, oxidative stress, autophagy, apoptosis, and neuroinflammation. This information will provide the basis of lnc RNA-based disease diagnosis and drug treatment for PD.展开更多
Congenital hydrocephalus is a major neurological disorder with high rates of morbidity and mortality;however,the underlying cellular and molecular mechanisms remain largely unknown.Reproducible animal models mirroring...Congenital hydrocephalus is a major neurological disorder with high rates of morbidity and mortality;however,the underlying cellular and molecular mechanisms remain largely unknown.Reproducible animal models mirroring both embryonic and postnatal hydrocephalus are also limited.Here,we describe a new mouse model of congenital hydrocephalus through knockout ofβ-catenin in Nkx2.1-expressing regional neural progenitors.Progressive ventriculomegaly and an enlarged brain were consistently observed in knockout mice from embryonic day 12.5 through to adulthood.Transcriptome profiling revealed severe dysfunctions in progenitor maintenance in the ventricular zone and therefore in cilium biogenesis afterβ-catenin knockout.Histological analyses also revealed an aberrant neuronal layout in both the ventral and dorsal telencephalon in hydrocephalic mice at both embryonic and postnatal stages.Thus,knockout ofβ-catenin in regional neural progenitors leads to congenital hydrocephalus and provides a reproducible animal model for studying pathological changes and developing therapeutic interventions for this devastating disease.展开更多
基金supported by grants from Simons Foundation (SFARI 479754),CIHR (PJT-180565)the Scottish Rite Charitable Foundation of Canada (to YL)funding from the Canada Research Chairs program。
文摘The mechanistic target of rapamycin(m TOR) is a serine/threonine kinase that plays a pivotal role in cellular growth, proliferation, survival, and metabolism. In the central nervous system(CNS), the mTOR pathway regulates diverse aspects of neural development and function. Genetic mutations within the m TOR pathway lead to severe neurodevelopmental disorders, collectively known as “mTORopathies”(Crino, 2020). Dysfunctions of m TOR, including both its hyperactivation and hypoactivation, have also been implicated in a wide spectrum of other neurodevelopmental and neurodegenerative conditions, highlighting its importance in CNS health.
基金supported by the grants from the Ministry of Science and Technology,China(No. 2009CB825402,2010CB529603)National Natural Science Foundation of China(No. 30900845)
文摘The nervous system is a complex network with many types of neurons and numerous synaptic connections.The present knowledge on how neurons recognize specific targets and form such an intricate network is still limited.The Down syndrome cell adhesion molecule （DSCAM） belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients.DSCAM plays important roles in neural development,including dendritic patterning and self-avoidance,axon guidance and branching,axon target recognition and synaptic formation.However,the functional mechanisms and the underlying signaling pathways are still largely unknown.Here the functions of DSCAM in neural development were reviewed.Future research for better understanding DSCAM function and the relevance of DSCAM to human diseases was also discussed.
基金supported by a grant from NIH(NINDSgrant number R15NS098389 to KW)
文摘Receptor for activated C kinase 1（RACK1）is an evolutionarily conserved scaffolding protein within the tryptophan-aspartate（WD）repeat family of proteins.RACK1 can bind multiple signaling molecules concurrently,as well as stabilize and anchor proteins.RACK1 also plays an important role at focal adhesions,where it acts to regulate cell migration.In addition,RACK1 is a ribosomal binding protein and thus,regulates translation.Despite these numerous functions,little is known about how RACK1 regulates nervous system development.Here,we review three studies that examine the role of RACK1 in neural development.In brief,these papers demonstrate that（1）RACK-1,the C.elegans homolog of mammalian RACK1,is required for axon guidance;（2）RACK1 is required for neurite extension of neuronally differentiated rat PC12cells;and（3）RACK1 is required for axon outgrowth of primary mouse cortical neurons.Thus,it is evident that RACK1 is critical for appropriate neural development in a wide range of species,and future discoveries could reveal whether RACK1 and its signaling partners are potential targets for treatment of neurodevelopmental disorders or a therapeutic approach for axonal regeneration.
基金supported by NIH CORE Grant P30 EY08098 to the Department of Ophthalmology,University of Pittsburgh,the Eye and Ear Foundation of Pittsburgh (to KCC)。
文摘SRY-related HMG-box(Sox) transcription factors are known to regulate central nervous system development and are involved in several neurological diseases.Post-translational modification of Sox proteins is known to alter their functions in the central nervous system.Among the different types of post-translational modification,small ubiquitin-like modifier(SUMO) modification of Sox proteins has been shown to modify their transcriptional activity.Here,we review the mechanisms of three Sox proteins in neuronal development and disease,along with their transcriptional changes under SUMOylation.Across three species,lysine is the conserved residue for SUMOylation.In Drosophila,SUMOylation of Sox N plays a repressive role in transcriptional activity,which impairs central nervous system development.However,de SUMOylation of Sox E and Sox11 plays neuroprotective roles,which promote neural crest precursor formation in Xenopus and retinal ganglion cell differentiation as well as axon regeneration in the rodent.We further discuss a potential translational therapy by SUMO site modification using AAV gene transduction and Clustered regularly interspaced short palindromic repeats-Cas9 technology.Understanding the underlying mechanisms of Sox SUMOylation,especially in the rodent system,may provide a therapeutic strategy to address issues associated with neuronal development and neurodegeneration.
基金Key Technologies Research & Development Program of Shanxi Province, No.041074
文摘BACKGROUND： Exposure to low-level lead has a toxic effect on the development of neonates, which has attracted wide attention. Colostrum lead level can be used as the indication of lead exposure. OBJECTIVE： To observe the relationship of colostrum lead level and the neurobehavioral development of infants. DESIGN： A prospective control observation. SETTING： Center for Maternal and Child Health, Shanxi Provincial Children＇s Hospital. PARTICIPANTS： Totally 128 neonates of full-term normal delivery, 76 male and 52 female, from Shanxi Provincial Maternal and Child Health Center and Jiexiu Maternal and Child Health Center were involved in this study. All the involved neonates had no peripartal ischemic/hypoxic history or fetus intrauterine developmental lag. Pregnant women had no various acute and chronic diseases in pregnancy, family history of neurological disease or occupational lead exposure. 128 portions of colostrum sample of full-term normal delivery were collected. Informed consents of detected items were obtained from the puerperants and their relatives. METHODS： ① Experimental grouping： Lead level in the colostrum was determined by atomic absorption spectrometry. According to lead level in the colostrum, the neonates were classified into two exposure groups of greater than or equal to 0.24 μmol/L in a high-level lead group and less than 0.24 μ mol/L in a low-level lead group. ② Experimental evaluation： Mental developmental index （MDI） and psychological developmental index （PDI） of 3-month-old infants were evaluated with Bayley Scales of Infant Development （BSID）. The relationships of MDI, PDI and colostrum lead level were performed correlation regression analysis; The relationship of colostrum lead level and development was performed multi-factor analysis with family environment and health questionnaires. MAIN OUTCOME MEASURES： ① Evaluation results of MDI and PDI. ② Multi-factor analysis results. RESULTS： Totally 128 neonates were involved in the study. Ten and eleven neonates were lost due to emigration in the high-level lead group and low-level lead group respectively, and the other 107 neonates participated in the final analysis. ① MDI and PDI in the high-level lead group were significantly lower than those in the low-level lead group, respectively （P 〈 0.01）; Regression analysis results showed that two developmental indexes were statistically negatively correlated with colostrum lead level （regression equation y = 1.9＋0.01x1,-0.04x2,＋0.04x3,＋0.03x4）. ② Four variables of the factors included by family environment and health questionnaires were taken into equation. Large maternal age, irrational dietary pattern in pregnancy and pollution degree of habitation environment in pregnancy were the risk factors of colostrum lead level （partial regression coefficien t =0.598 4,0.426 8,0.306 7,P 〈 0.05-0.01）, and calcium supplementation in pregnancy was a protective factor （partial regression coefficien t =-0.455 8, P 〈 0.01）. CONCLUSION： High colostrum lead level will have adverse effects on the early development of neonates; Large maternal age, irrational dietary pattern in pregnancy and pollution degree of habitation environment in pregnancy are the risk factors of colostrum lead level, and calcium supplementation in pregnancy was a protective factor.
基金supported by grants from the Program for New Century Excellent Talents in University, Ministry of Education of China (NCET-09-0109)the National Natural Science Foundation of China (31070955)+1 种基金the Doctoral Fund of the Ministry of Education of China (21310045)the Fundamental Research Funds for the Central Universities, Ministry of Education of China (21610604 and 21609101)
文摘flamingo is among the ＇core＇ planar cell-polarity genes, protein of which belongs to a unique cadherin subfamily. In contrast to the classic cadherins, composed of several extracellular cadherin repeats, one transmembrane domain and one cytoplasmic segment linked to catenin binding, Drosophila Flamingo has seven transmembrane segments and a cytoplasmic tail with no catenin-binding sequence. In Drosophila, Flamingo has pleotropic roles in controlling epithelial polarity and neuronal morphogenesis. Three mammalian orthologs of flamingo, Celsrl-3, are widely expressed in the nervous system. Recent work has shown that Celsrl-3 play important roles in neural development, such as in axon guidance, neuronal migration, and cilium polarity. CeIsrl-3 single-gene knockout mice exhibit different phenotypes, but there are cooperative interactions among these genes.
文摘The matrix metalloproteinases（MMPs） are a family of zinc-dependent endopeptidases originally characterized as secreted proteases responsible for degrading extracellular matrix proteins.Their canonical role in matrix remodelling is of significant importance in neural development and regeneration,but emerging roles for MMPs,especially in signal transduction pathways,are also of obvious importance in a neural context.Misregulation of MMP activity is a hallmark of many neuropathologies,and members of every branch of the MMP family have been implicated in aspects of neural development and disease.However,while extraordinary research efforts have been made to elucidate the molecular mechanisms involving MMPs,methodological constraints and complexities of the research models have impeded progress.Here we discuss the current state of our understanding of the roles of MMPs in neural development using recent examples and advocate a phylogenetically diverse approach to MMP research as a means to both circumvent the challenges associated with specific model organisms,and to provide a broader evolutionary context from which to synthesize an understanding of the underlying biology.
基金National Natural Science Foundation of China(90919039,C120106)the National Institute for Basic Biology,Japan,for the Xl073b24 clone.
文摘Xenopus ZFP36L1(zinc finger protein 36,C3H type-like 1)belongs to the ZFP36 family of RNA-binding proteins,which contains two characteristic tandem CCCH-type zinc-finger domains.The ZFP36 proteins can bind AU-rich elements in 3'untranslated regions of target mRNAs and promote their turnover.However,the expression and role of ZFP36 genes during neural development in Xenopus embryos remains largely unknown.The present study showed that Xenopus ZFP36L1 was expressed at the dorsal part of the forebrain,forebrain-midbrain boundary,and midbrain-hindbrain boundary from late neurula stages to tadpole stages of embryonic development.Overexpression of XZFP36L1 in Xenopus embryos inhibited neural induction and differentiation,leading to severe neural tube defects.The function of XZP36L1 requires both its zinc finger and C terminal domains,which also affect its subcellular localization.These results suggest that XZFP36L1 is likely involved in neural development in Xenopus and might play an important role in post-transcriptional regulation.
基金Foundation items： This work was supported by National Natural Science Foundation of China （90919039 C120106） Acknowledgements We thank the National Institute for Basic Biology, Japan, for the X1073h24 clone.
文摘Xenopus ZFP36L1 （zinc finger protein 36, C3H type-like 1） belongs to the ZFP36 family of RNA-binding proteins, which contains two characteristic tandem CCCH-type zinc-finger domains. The ZFP36 proteins can bind AU-rich elements in 3＇ untranslated regions of target mRNAs and promote their turnover. However, the expression and role of ZFP36 genes during neural development in Xenopus embryos remains largely unknown. The present study showed that Xenopus ZFP36L1 was expressed at the dorsal part of the forebrain, forebrain-midbrain boundary, and midbrain-hindbrain boundary from late neurula stages to tadpole stages of embryonic development. Overexpression of XZFP36L1 in Xenopus embryos inhibited neural induction and differentiation, leading to severe neural tube defects. The function of XZP36L1 requires both its zinc finger and C terminal domains, which also affect its subcellular localization. These results suggest that XZFP36L1 is likely involved in neural development in Xenopus and might play an important role in post-transcriptional regulation.
基金Supported by the Natural Science Foundation of Anhui Province,No.2008085MH251Key Research and Development Project of Anhui Province,No.202004J07020037+1 种基金Anhui Provincial Institute of Translational Medicine,No.2021zhyx-C19National Undergraduate Innovation and Entrepreneurship training program,No.202010366016。
文摘Different fates of neural stem/progenitor cells(NSPCs)and their progeny are determined by the gene regulatory network,where a chromatin-remodeling complex affects synergy with other regulators.Here,we review recent research progress indicating that the BRG1/BRM-associated factor(BAF)complex plays an important role in NSPCs during neural development and neural developmental disorders.Several studies based on animal models have shown that mutations in the BAF complex may cause abnormal neural differentiation,which can also lead to various diseases in humans.We discussed BAF complex subunits and their main characteristics in NSPCs.With advances in studies of human pluripotent stem cells and the feasibility of driving their differentiation into NSPCs,we can now investigate the role of the BAF complex in regulating the balance between self-renewal and differentiation of NSPCs.Considering recent progress in these research areas,we suggest that three approaches should be used in investigations in the near future.Sequencing of whole human exome and genome-wide association studies suggest that mutations in the subunits of the BAF complex are related to neurodevelopmental disorders.More insight into the mechanism of BAF complex regulation in NSPCs during neural cell fate decisions and neurodevelopment may help in exploiting new methods for clinical applications.
基金supported by grants from the Ministry of Education,Culture,Sports,Science and Technology in Japan and Naito Foundation to TCthe Japan Society for the Promotion of Science to MO and TC
文摘Basic helix-loop-helix （bHLH） transcription factors regulate the differentiation of various tissues in a vast diversity of species. The bHLH protein Atonal was first identified as a proneural gene involved in the formation of mechanosensory cells and photoreceptor cells in Drosophila （larman et al., 1993, 1994）. Atonal is expressed in sensory organ precursors and is required and sufficient for the development of chordotonal organs （Jar- man et al., 1993）. Moreover, Atonal expression is observed in the developing eye and is essential for the differentiation of R8 photoreceptors, which are the first photoreceptors that appear during development. Atonal is not involved in the formation of other photoreceptors （R1-R7） directly. However, R8 photore- ceptors recruit other photoreceptors from the surrounding cells （Jarman et al., 1994）.
基金Baotou Hygiene Scientific and Technological Program(wsjkk2022082).
文摘Objective:To explore the combined effects of multisensory intervention and amplitude integrated electroencephalogram monitoring on the maturation and evaluation of brain and neural development in premature infants of different gestational ages.Methods:The controlled trial was carried out in 62 premature infants from January to February of 2023 in Genertec AMHT-Baogang Hospital.The premature infants were divided into two groups according to the gestational age:32-33^(+6W)(Group A)and 34-36^(+6W)(Group B).By use of random number table method,each group was subdivided into the control group and the experimental group.The control group was monitored with aEEG within 1 day and the following 7 days after birth.The experimental group was monitored with aEEG within 1 day and the following 7 days after multisensory intervention(MS)to observe the change of aEEG parameters,in order to explore the effect of MS intervention on brain development maturity.The Neonatal Behavioral Neurological Assessment(NBNA)score was performed at 40 weeks of corrected gestational age in both groups.Results:The amplitude voltage,the total aEEG score and the sleep-wake cycle score in the experimental group were higher than those in the control group(p<.05).The total NBNA score in the experimental group was higher than that in the control group.Conclusions:The multi-sensory intervention is a simple and feasible method of development support nursing,it can improve the total NBNA score of premature infants,which can promote the brain development in premature infants and improve their neurodevelopmental behavior.
基金Dr.Hui Fu was supported by the National Natural Science Foundation of China,No.81371338by Open Research Fund Program of Hubei-MOST KLOS & KLOBMEDr.Zu-neng Lu was supported by grants from Health and Family Planning Commission of Hubei Province scientific research project,No.WJ2015MA007
文摘There are few studies on the membrane protein Ankfyl. We have found Ankfyl is specifically expressed in neural stem/precursor cells during early development in mice （murine）. To further explore Ankfyl function in neural development, we developed a gene knockout mouse with a mixed Balb/C and C57/BL6 genetic background. Using immunofluorescence and in situ hybridization, neural defects were absent in mixed genetic Ankfyl null mice during development and in adults up to 2 months old. However, Ankfyl gene knockout mice with a pure genetic background were found to be lethal in the C57/BL6 inbred mice embryos, even after seven generations of backcrossing. Polymerase chain reaction confirmed homozygotes were unattainable as early as embryonic day 11.5. We conclude that Ankfyl protein is dispensable in neural stem/precursor ceils, but could be critical for early embryonic murine development, depending on the genetic background.
文摘Neural tube development comprises neural induction, neural epithelial cell proliferation, and apoptosis, as well as migration of nerve cells. Too much or too little apoptosis leads to abnormal nervous system development. The present study analyzed expression and distribution of apoptotic-related factors, including Fas, FasL, and caspase-3, during human embryonic neural tube development. Experimental results showed that increased caspase-3 expression promoted neural apoptosis via a mitochondrial-mediated intrinsic pathway at 4 weeks during early human embryonic neural tube development. Subsequently, Fas and FasL expression increased during embryonic development. The results suggest that neural cells influence neural apoptosis through synergistic effects of extrinsic pathways. Therefore, neural apoptosis during the early period of neural tube development in the human embryo might be regulated by the death receptor induced apoptotic extrinsic pathways.
基金support from Science Foundation Ireland under grant No. SFI/IA/1537
文摘The mitogen-activated protein kinase（MAPK）pathways are a group of conserved intracellular signalling pathways present in most cells including neurons and glia.These pathways respond to a variety of stimuli including growth factors,cytokines and oxidative stress to generate appropriate cellular responses such as modulation of gene expression,cell proliferation,differentiation and survival as well as the stress response（Korhonen and Moilanen,2014）.
文摘A major basic research projectin the field of neurosciencewas launched on November26 last year at the Shanghai-basedInstitute of Neuroscience of the Chi-nese Academy of Sciences(CAS).
文摘High-risk infants,from fetal stage to 3-year-old,face severe physical and mental development threats due to biological,psychological,or environmental factors.These threats can lead to developmental delay and cognitive impairment,affecting their future quality of life and social integration.Scientific health management,with nutritional intervention as a key part,is urgently needed.Nutritional intervention,through targeted supplementation and feeding guidance,can optimize their development,avoid nutritional-related deviations,reduce long-term disease risk,and lay a healthy growth foundation.This study analyzes the positive effects of nutritional intervention on high-risk infants’physical growth,neural development,and disease prevention,providing scientific evidence for optimizing clinical follow-up strategies.
基金CAMS Innovation Fund for Medical Sciences,Grant/Award Number:2017-I2M-2-005 and 2016-I2M-2-006Beijing Natural Science Foundation,Grant/Award Number:5171001
文摘Long noncoding RNAs(lnc RNAs) are RNA molecules comprising more than 200 nucleotides, which are not translated into proteins. Many studies have shown that lnc RNAs are involved in regulating a variety of biological processes, including immune, cancer, stress, development and differentiation at the transcriptional, epigenetic or post-transcriptional levels. Here, we review the role of lnc RNAs in the process of neurodevelopment, neural differentiation, synaptic function, and pathogenesis of Parkinson’s disease(PD). These pathomechanisms include protein misfolding and aggregation, disordered protein degradation, mitochondrial dysfunction, oxidative stress, autophagy, apoptosis, and neuroinflammation. This information will provide the basis of lnc RNA-based disease diagnosis and drug treatment for PD.
基金This work was supported by grants from the National Key Research and Development Program of China(2018YFA0108000 and 2019YFA0110300)the National Natural Science Foundation of China(8205020,32000689,31400934,31771132,31872760,31801204,and 31800858)+3 种基金the Science and Technology Commission of Shanghai Municipality(19JC1415100 and 21140902300)the Shanghai Municipal Education Commission(C120114)China Postdoctoral Science Foundation(2017M621526)the Fundamental Research Funds for the Central Universities,and the Major Program of Development Fund for Shanghai Zhangjiang National Innovation Demonstration Zone(Stem Cell Strategic Biobank and Clinical Translation Platform of Stem Cell Technology,ZJ2018-ZD-004).
文摘Congenital hydrocephalus is a major neurological disorder with high rates of morbidity and mortality;however,the underlying cellular and molecular mechanisms remain largely unknown.Reproducible animal models mirroring both embryonic and postnatal hydrocephalus are also limited.Here,we describe a new mouse model of congenital hydrocephalus through knockout ofβ-catenin in Nkx2.1-expressing regional neural progenitors.Progressive ventriculomegaly and an enlarged brain were consistently observed in knockout mice from embryonic day 12.5 through to adulthood.Transcriptome profiling revealed severe dysfunctions in progenitor maintenance in the ventricular zone and therefore in cilium biogenesis afterβ-catenin knockout.Histological analyses also revealed an aberrant neuronal layout in both the ventral and dorsal telencephalon in hydrocephalic mice at both embryonic and postnatal stages.Thus,knockout ofβ-catenin in regional neural progenitors leads to congenital hydrocephalus and provides a reproducible animal model for studying pathological changes and developing therapeutic interventions for this devastating disease.
