Objective To investigate the cell proliferation and differentiation in the developing brain of mouse. Methods C57/BL6 mice were divided into 3 groups at random. Bromodeoxyuridine （BrdU） was injected into the brains ...Objective To investigate the cell proliferation and differentiation in the developing brain of mouse. Methods C57/BL6 mice were divided into 3 groups at random. Bromodeoxyuridine （BrdU） was injected into the brains in different development periods once a day for 7 d. The brains were retrieved 4 weeks after the last BrdU injection. Immunohistochemical and immunofluorescent studies were carried out for detecting cell proliferation （BrdU） and cell differentiation （NeuN, APC, lbal, and S 100β）, respectively. Results The number of BrdU labeled cells decreased significantly with the development of the brain. Cell proliferation was prominent in the cortex and striatum. A small portion of BrdU and NeuN double labeled cells could be detected in the cortex at the early stage of development, and in the striatum and CA of the hippocampus in all groups. The majority of BrdU labeled cells were neuroglia, and the number of neuroglia cells decreased dramatically with brain maturation. Neurogenesis is the major cytogenesis in the dentate gyrus. Conclusion These results demonstrated that cell proliferation, differentiation and survival were age and brain region related.展开更多
Tree shrews（also named banxrings）,the small mammals native to Southeast Asia,are featured by moderate size,easy breeding,high reproductivity and close genetic background to primates（Xu et al.,2012;Xiao et al.,2017...Tree shrews（also named banxrings）,the small mammals native to Southeast Asia,are featured by moderate size,easy breeding,high reproductivity and close genetic background to primates（Xu et al.,2012;Xiao et al.,2017）.Tiee shrews possess both conserved and unique features compared to primates,and thus will become a suitable animal model with modest cost-effciency（Yao,2017）.展开更多
Children are being exposed to an increasingly greater variety of anesthetics with advances in pediatric and obstetric surgery. Recent animal and retrospective human data suggest that the general anes- thetics commonly...Children are being exposed to an increasingly greater variety of anesthetics with advances in pediatric and obstetric surgery. Recent animal and retrospective human data suggest that the general anes- thetics commonly used in pediatric medicine could he damaging to the developing brain when used at clinical concentrations. In viw~ primate and rodent models have shown that neonatal exposure to clinical concentrations of anesthetics causes neural apoptosis and long-term cognitive impairment. Many general anesthetics.展开更多
The human brain undergoes a complex and dynamic developmental process from birth through adolescence,driven by molecular and cellular mechanisms that shape its structure and function.Magnetic resonance imaging(MRI)has...The human brain undergoes a complex and dynamic developmental process from birth through adolescence,driven by molecular and cellular mechanisms that shape its structure and function.Magnetic resonance imaging(MRI)has become an essential non-invasive tool for studying pediatric brain development and detecting neurological disorders.However,pediatric neuroimaging presents unique challenges,including motion artifacts,small anatomical structures,and immature tissue properties,necessitating specialized MRI techniques.This review provides an overview of recent advancements in MRI hardware,acquisition strategies,and analytical methods optimized for pediatric brain imaging.Furthermore,it summarizes the applications of these techniques in understanding normal brain development,neurodevelopmental disorders,and the impact of early-life risk factors.This review highlights the progresses in pediatric MRI,emphasizing its critical role in advancing our understanding of pediatric brain development and neurological health.It also outlines the challenges and future directions in pediatric MRI to further improve imaging precision and clinical utility.展开更多
In the present study, 7 day postnatal C57/BL6 wild-type mice （hyperoxia group） and 7 day postnatal N-methyI-D-aspartate receptor subtype 3A knockout mice （NR3A KO group） were exposed to 75% oxygen and 15% nitrogen...In the present study, 7 day postnatal C57/BL6 wild-type mice （hyperoxia group） and 7 day postnatal N-methyI-D-aspartate receptor subtype 3A knockout mice （NR3A KO group） were exposed to 75% oxygen and 15% nitrogen in a closed container for 5 days. Wild-type mice raised in normoxia served as controls. TdT-mediated dUTP nick end labeling （TUNEL）/neuron-specific nuclear protein （NeuN） and 5-bromo-2＇-deoxyuridine （BrdU）/NeuN immunofluorescence staining showed that the number of apoptotic cells and the number of proliferative cells in the dentate subgranular zone significantly increased in the hyperoxia group compared with the control group. However, in the same hyperoxia environment, the number of apoptotic cells and the number of proliferative cells significantly decreased in the NR3A KO group compared with hyperoxia group. TUNEL＋/NeuN＋ and BrdU＋/NeuN~ cells were observed in the NR3A KO and the hyperoxia groups. These results demonstrated that the NR3A gene can promote cell apoptosis and mediate the potential damage in the developing brain induced by exposure to non-physiologically high concentrations of oxygen.展开更多
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
We hypothesized that the P2X7 receptor may be the target of isoflurane, so we investigated the roles of the P2X7 receptor and inositol triphosphate receptor in calcium overload and neuronal apoptosis induced by isoflu...We hypothesized that the P2X7 receptor may be the target of isoflurane, so we investigated the roles of the P2X7 receptor and inositol triphosphate receptor in calcium overload and neuronal apoptosis induced by isoflurane in cultured embryonic rat hippocampal neurons. Results showed that isoflurane induced widespread neuronal apoptosis and significantly increased cytoplasmic Ca^2＋ Blockade of P2X7 receptors or removal of extracellular Ca^2＋ combined with blockade of inositol triphosphate receptors completely inhibited apoptosis or increase in cytoplasmic Ca^2＋. Removal of extracellular Ca^2＋ or blockade of inositol triphosphate receptor alone could partly inhibit these effects of isoflurane. Isoflurane could directly activate P2X7-gated channels and induce inward currents, but did not affect the expression of P2X7 receptor protein in neurons. These findings indicate that the mechanism by which isoflurane induced neuronal apoptosis in rat developing brain was mediated by intracellular calcium overload, which was caused by P2X7 receptor mediated calcium influx and inositol triphosphate receptor mediated calcium release.展开更多
Using the specific affinity of tubulin for colchicine and the strong absorption of tubulin to DEAE ion exchangers at neutral pH and moderate ionic strength,the amounts of tubulin in the brain from both mice and chicks...Using the specific affinity of tubulin for colchicine and the strong absorption of tubulin to DEAE ion exchangers at neutral pH and moderate ionic strength,the amounts of tubulin in the brain from both mice and chicks during different developing stages were measured by ~3H-colchicine assay (expressed as colchicine binding activity).The results show that the rate oftubulin synthesis reached a peak value during the critical period of brain development.This is exactly the period during which the organization and function of thyroid are being perfected.Besides,during breeding period,the difference of tubulin contents between male and female is significant(P<0.001).The synthesis of tubulin is strictly sex dependent(this phenomenon appeared only during sex maturation stage).It is suggested that sexual hormones might exert their effect on tubulin synthesis.展开更多
Understanding the fundamental processes of human brain development and diseases is of great importance for our health.However,existing research models such as non-human primate and mouse models remain limited due to t...Understanding the fundamental processes of human brain development and diseases is of great importance for our health.However,existing research models such as non-human primate and mouse models remain limited due to their developmental discrepancies compared with humans.Over the past years,an emerging model,the“brain organoid”integrated from human pluripotent stem cells,has been developed to mimic developmental processes of the human brain and disease-associated phenotypes to some extent,making it possible to better understand the complex structures and functions of the human brain.In this review,we summarize recent advances in brain organoid technologies and their applications in brain development and diseases,including neurodevelopmental,neurodegenerative,psychiatric diseases,and brain tumors.Finally,we also discuss current limitations and the potential of brain organoids.展开更多
Brain development and aging are associated with alterations in multiple epigenetic systems, including DNA methylation and demethylation patterns. Here, we observed that the levels of the 5- hydroxymethylcytosine （5hm...Brain development and aging are associated with alterations in multiple epigenetic systems, including DNA methylation and demethylation patterns. Here, we observed that the levels of the 5- hydroxymethylcytosine （5hmC） ten-eleven transtocation （TET） enzyme-mediated active DNA demethylation products were dynamically changed and involved in postnatal brain development and aging in tree shrews （Tupaia belangeri chinensis）. The levels of 5hmC in multiple anatomic structures showed a gradual increase throughout postnatal development, whereas a significant decrease in 5hmC was found in several brain regions in aged tree shrews, including in the prefrontal cortex and hippocampus, but not the cerebellum. Active changes in Tet mRNA levels indicated that TET2 and TET3 predominantly contributed to the changes in 5hmC levels. Our findings provide new insight into the dynamic changes in 5hmC levels in tree shrew brains during postnatal development and aging processes.展开更多
Background:Emerging research supports the idea that exercise positively affects neurodevelopment.However,the mechanisms linking exercise with brain health are largely unknown.We aimed to investigate the effect of exer...Background:Emerging research supports the idea that exercise positively affects neurodevelopment.However,the mechanisms linking exercise with brain health are largely unknown.We aimed to investigate the effect of exercise on(a)blood biomarkers selected based on previous evidence(brainderived neurotrophic factor,β-hydroxybutyrate(BHB),cathepsin B(CTSB),kynurenine,fibroblast growth factor 21(FGF21),soluble vascular cell adhesion molecule-1(sVCAM-1));and(b)a panel of 92 neurology-related proteins(discovery analysis).We also investigated whether changes in these biomarkers mediate the effects of exercise on brain health(hippocampal structure and function,cognitive performance,and mental health).Methods:We randomized 81 overweight/obese children(10.1±1.1 years,41%girls)into 2 groups:either 20 weeks of aerobic plus resistance exercise or control.Candidate biomarkers were assessed using enzyme-linked immunosorbent assay(ELISA)for kynurenine,FGF21,and CTSB;colorimetry forβ-hydroxybutyrate;and XMap for brain-derived neurotrophic factor and soluble vascular cell adhesion molecule-1.The92 neurology-related proteins were analyzed by an antibody-based proteomic analysis.Results:Our intervention had no significant effect on candidate biomarkers(all p>0.05).In the discovery analysis,a reduction in circulating macrophage scavenger receptor type-I was observed(standardized differences between groups=-0.3,p=0.001).This effect was validated using ELISA methods(standardized difference=-0.3,p=0.01).None of the biomarkers mediated the effects of exercise on brain health.Conclusions:Our study does not support a chronic effect of exercise on candidate biomarkers.We observed that while chronic exercise reduced the levels of macrophage scavenger receptor type-Ⅰ,it did not mediate the effects of exercise on brain health.Future studies should explore the implications of this novel biomarker for overall health.展开更多
Glial cells are crucial for maintaining central nervous system(CNS)homeostasis.They actively participate in immune responses,as well as form functional barriers,such as blood-brain barrier(BBB),which restrict the entr...Glial cells are crucial for maintaining central nervous system(CNS)homeostasis.They actively participate in immune responses,as well as form functional barriers,such as blood-brain barrier(BBB),which restrict the entry of pathogens and inflammatory mediators into the CNS.In general,viral infections during the gestational period can alter the embryonic and fetal environment,and the related inflammatory response may affect neurodevelopment and lead to behavioral dysfunction during later stage of life,as highlighted by our group for Zika virus infection.Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)induces a cytokine storm and,during pregnancy,may be related to a more severe form of the coronavirus disease-19(COVID-19)and also to higher preterm birth rates.SARS-CoV-2 can also affect the CNS by inducing neurochemical remodeling in neural cells,which can compromise neuronal plasticity and synaptic function.However,the impact of SARS-CoV-2 infection during pregnancy on postnatal CNS,including brain development during childhood and adulthood,remains undetermined.Our group has recently highlighted the impact of COVID-19 on the expression of molecular markers associated with neuropsychiatric disorders,which are strongly related to the inflammatory response.Thus,based on these relationships,we discussed the impact of SARS-CoV-2 infection either during pregnancy or in critical periods of neurodevelopment as a risk factor for neurological consequences in the offspring later in life,focusing on the potential role of glial cells.Thus,it is important to consider future and long-term public health concerns associated with SARS-CoV-2 infection during pregnancy.展开更多
Objective To study the developmental changes of glutamic acid decarboxylase-67 （ GAD-67, a GABA synthetic enzyme） in normal and hypoxic ischemic （HI） brain. Methods C57/BL6 mice on postnatal day （P） 5, 9, 21 and...Objective To study the developmental changes of glutamic acid decarboxylase-67 （ GAD-67, a GABA synthetic enzyme） in normal and hypoxic ischemic （HI） brain. Methods C57/BL6 mice on postnatal day （P） 5, 9, 21 and 60, corresponding developmentally to premature, term, juvenile and adult human brain were investigated by using both Western blot and immunohistochemistry methods either in normal condition or after hypoxic ischemic insult. Results The immunoreactivity of GAD67 was up regulated with brain development and significant difference was seen between mature （P21, P60） and immature （P5, P9） brain. GAD67 immunoreactivity decreased in the ipsilateral hemisphere in all the ages after hypoxia ischemia （HI） insult, but, significant decrease was only seen in the immature brain. Double labeling of GAD67 and cell death marker, TUNEL, in the cortex at 8h post-HI in the P9 mice showed that （15.6±7.0）% TUNEL positive cells were GAD67 positive which was higher than that of P60 mice. Conclusion These data suggest that GABAergic neurons in immature brain were more vulnerable to HI insult than that of mature brain.展开更多
With the advent of modern techniques, drugs, and monitoring, general anesthesia has come to be considered an unlikely cause of harm, particularly for healthy patients. While this is largely true, newly emerging clinic...With the advent of modern techniques, drugs, and monitoring, general anesthesia has come to be considered an unlikely cause of harm, particularly for healthy patients. While this is largely true, newly emerging clinical and laboratory studies have sug- gested that exposure to anesthetic agents during early childhood may have long-lasting adverse effects on cognitive function. This concern has been the focus of intense study in the field of anesthesia research. A recent high-profile review by Rappaport et al. （2015） concluded that while many questions remain un- answered, there is strong evidence from laboratory studies that commonly used anesthetics interfere with brain development and that clinical studies suggest a correlation between early childhood exposure to these agents and subsequent effects on learning and cognition. The issue is of sufficient public health importance that a public-private partnership known as Smar- Tots （Strategies for Mitigating Anesthesia-Related Neurotoxicity in Tots） was developed by the FDA to study pediatric anesthetic neurotoxicity. The mechanism of injury underlying this phe- nomenon has yet to be fully elucidated, and there is evidence to suggest that anesthetics may have direct cytotoxic effects on neurons leading to cell death or suppressed neurogenesis （Strat- mann et al., 2010） and that they may interfere with key pro- cesses in neuronal growth and development that underlie brain circuit development （Wagner et al., 2014）.展开更多
Tetrabromobisphenol A(TBBPA)is a widely used brominated flame retardant.There is evidence showing that TBBPA can exert thyroid disrupting effects in mammals,but different results were also reported,along with inconsis...Tetrabromobisphenol A(TBBPA)is a widely used brominated flame retardant.There is evidence showing that TBBPA can exert thyroid disrupting effects in mammals,but different results were also reported,along with inconsistent reports regarding its neurotoxicity.Here,we investigated thyroid disrupting effects and neurotoxicity of TBBPA(5,50,500μg/(kg·day))to male mice following maternal and direct exposure through drinking water,with the antithyroid drug propylthiouracil(PTU)as the positive control.On postnatal day(PND)15,we expectedly observed severe thyroid compensatory hyperplasia and cerebellar developmental retardation in PTU-treated pups.The highest dose of TBBPA also caused thyroid histological alteration but had no effects on cerebellar development in terms of Purkinje cell morphology and the thickness of the internal granular layer and the molecular layer of the cerebellum.During puberty and adulthood,the thyroid morphological alterations became more pronounced in the TBBPA-treated animals,accompanied by decreased serum thyroid hormone levels.Furthermore,the 50 and 500μg/(kg·day)TBBPA groups showed a significant decrease in the serum level of serotonin,a neurotransmitter associated with anxiety behaviors.Correspondingly,the highest dose group displayed anxiety-like behaviors in the elevated plus-maze test on PND 35,but this neurobehavioral alteration disappeared on PND 56.Moreover,no changes in neurobehavioral parameters tested were found in TBBPAtreated animals at puberty and adulthood.Altogether,all observations show that TBBPA can exert thyroid disrupting effects but has little overt impact on brain development and neurobehaviors in mice,suggesting that thyroid disruption does not necessarily cause overtly adverse neurodevelopmental outcomes.展开更多
Genomic mosaicism describes the phenomenon where some but not all cells within a tissue harbor unique genetic mutations.Traditionally,research focused on the impact of genomic mosaicism on clinical phenotype—motivate...Genomic mosaicism describes the phenomenon where some but not all cells within a tissue harbor unique genetic mutations.Traditionally,research focused on the impact of genomic mosaicism on clinical phenotype—motivated by its involvement in cancers and overgrowth syndromes.More recently,we increasingly shifted towards the plethora of neutral mosaic variants that can act as recorders of cellular lineage and environmental exposures.Here,we summarize the current state of the field of genomic mosaicism research with a special emphasis on our current understanding of this phenomenon in brain development and homeostasis.Although the field of genomic mosaicism has a rich history,technological advances in the last decade have changed our approaches and greatly improved our knowledge.We will provide current definitions and an overview of contemporary detection approaches for genomic mosaicism.Finally,we will discuss the impact and utility of genomic mosaicism.展开更多
BACKGROUND Understanding the impact of early sensory deficits on brain development is essential for understanding developmental processes and developing potential interventions.While previous studies have looked into ...BACKGROUND Understanding the impact of early sensory deficits on brain development is essential for understanding developmental processes and developing potential interventions.While previous studies have looked into the impact of prenatal experiences on language development,there is a lack of research on how these experiences affect early language and brain function development in individuals with sensorineural hearing loss(SNHL).AIM To investigate SNHL effects on early brain development and connectivity in 4-month-olds vs healthy newborns and controls.METHODS The research involved analyzing the functional brain networks of 65 infants,categorized into three groups:28 healthy newborns,224-month-old participants with SNHL,and 15 age-matched healthy participants.The resting-state functional connectivity was measured and compared between the groups using functional near-infrared spectroscopy and graph theory to assess the brain network properties.RESULTS Significant differences were found in resting-state functional connectivity between participants with SNHL and age-matched controls,indicating a developmental lag in brain connectivity for those with SNHL.Surprisingly,SNHL participants showed better connectivity development compared to healthy newborns,with connectivity strengths of 0.13±0.04 for SNHL,0.16±0.08 for controls,and 0.098±0.04 for newborns.Graph theory analysis revealed enhanced global brain network properties for the SNHL group,suggesting higher communication efficiency at 4 months.No significant differences were noted in network properties between 4-month-old SNHL participants and neonates.A unique pattern of central hubs was observed in the SNHL group,with 2 hubs in the left hemisphere compared to 6 in controls.CONCLUSION 4-month-old infants with SNHL have a distinct brain network pattern with efficient long-distance information transmission but less effective local communication compared to age-matched controls.展开更多
Microglia are the resident immune cells of the central nervous system （CNS）, In the normal state, microglia have a ramified shape and con- tinuously survey the conditions of the brain.
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).
基金This work was supported by the grant of National Natural Science Foundation of China （No. 30470598）.
文摘Objective To investigate the cell proliferation and differentiation in the developing brain of mouse. Methods C57/BL6 mice were divided into 3 groups at random. Bromodeoxyuridine （BrdU） was injected into the brains in different development periods once a day for 7 d. The brains were retrieved 4 weeks after the last BrdU injection. Immunohistochemical and immunofluorescent studies were carried out for detecting cell proliferation （BrdU） and cell differentiation （NeuN, APC, lbal, and S 100β）, respectively. Results The number of BrdU labeled cells decreased significantly with the development of the brain. Cell proliferation was prominent in the cortex and striatum. A small portion of BrdU and NeuN double labeled cells could be detected in the cortex at the early stage of development, and in the striatum and CA of the hippocampus in all groups. The majority of BrdU labeled cells were neuroglia, and the number of neuroglia cells decreased dramatically with brain maturation. Neurogenesis is the major cytogenesis in the dentate gyrus. Conclusion These results demonstrated that cell proliferation, differentiation and survival were age and brain region related.
基金supported by the National Natural Science Foundation of China(No.31600841)the Shanghai brain-intelligence project from STCSM(16JC1420500)the Beijing brain project (Z161100002616004)
文摘Tree shrews（also named banxrings）,the small mammals native to Southeast Asia,are featured by moderate size,easy breeding,high reproductivity and close genetic background to primates（Xu et al.,2012;Xiao et al.,2017）.Tiee shrews possess both conserved and unique features compared to primates,and thus will become a suitable animal model with modest cost-effciency（Yao,2017）.
基金supported by the Japan Society for the Promotion of Science,Tokyo,JapanGrant No.23890054 and 25861361
文摘Children are being exposed to an increasingly greater variety of anesthetics with advances in pediatric and obstetric surgery. Recent animal and retrospective human data suggest that the general anes- thetics commonly used in pediatric medicine could he damaging to the developing brain when used at clinical concentrations. In viw~ primate and rodent models have shown that neonatal exposure to clinical concentrations of anesthetics causes neural apoptosis and long-term cognitive impairment. Many general anesthetics.
基金supported by the National Natural Science Foundation of China,Grant No.3242780005 and U24 A20754(DW)Key project of Agriculture and social development of Hangzhou,Grant No.20231203 A13(DW)+1 种基金Zhejiang Provincial Natural Science Foundation of China,Grant No.LY24H180002(HXZ)Shanghai Pilot Program for Basic Research—Chinese Academy of Science,Shanghai Branch,Grant No.JCYJ-SHFY-2022-014(HZ).
文摘The human brain undergoes a complex and dynamic developmental process from birth through adolescence,driven by molecular and cellular mechanisms that shape its structure and function.Magnetic resonance imaging(MRI)has become an essential non-invasive tool for studying pediatric brain development and detecting neurological disorders.However,pediatric neuroimaging presents unique challenges,including motion artifacts,small anatomical structures,and immature tissue properties,necessitating specialized MRI techniques.This review provides an overview of recent advancements in MRI hardware,acquisition strategies,and analytical methods optimized for pediatric brain imaging.Furthermore,it summarizes the applications of these techniques in understanding normal brain development,neurodevelopmental disorders,and the impact of early-life risk factors.This review highlights the progresses in pediatric MRI,emphasizing its critical role in advancing our understanding of pediatric brain development and neurological health.It also outlines the challenges and future directions in pediatric MRI to further improve imaging precision and clinical utility.
基金supported by the National Institutes of Health, USA, No. NS 045810, NS 057255the BasicClinical Scientific Research Foundation Program of the Capital Medical University, China, No. 2006JL19
文摘In the present study, 7 day postnatal C57/BL6 wild-type mice （hyperoxia group） and 7 day postnatal N-methyI-D-aspartate receptor subtype 3A knockout mice （NR3A KO group） were exposed to 75% oxygen and 15% nitrogen in a closed container for 5 days. Wild-type mice raised in normoxia served as controls. TdT-mediated dUTP nick end labeling （TUNEL）/neuron-specific nuclear protein （NeuN） and 5-bromo-2＇-deoxyuridine （BrdU）/NeuN immunofluorescence staining showed that the number of apoptotic cells and the number of proliferative cells in the dentate subgranular zone significantly increased in the hyperoxia group compared with the control group. However, in the same hyperoxia environment, the number of apoptotic cells and the number of proliferative cells significantly decreased in the NR3A KO group compared with hyperoxia group. TUNEL＋/NeuN＋ and BrdU＋/NeuN~ cells were observed in the NR3A KO and the hyperoxia groups. These results demonstrated that the NR3A gene can promote cell apoptosis and mediate the potential damage in the developing brain induced by exposure to non-physiologically high concentrations of oxygen.
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.
基金supported by the National Natural Science Foundation of China,No.30471657
文摘We hypothesized that the P2X7 receptor may be the target of isoflurane, so we investigated the roles of the P2X7 receptor and inositol triphosphate receptor in calcium overload and neuronal apoptosis induced by isoflurane in cultured embryonic rat hippocampal neurons. Results showed that isoflurane induced widespread neuronal apoptosis and significantly increased cytoplasmic Ca^2＋ Blockade of P2X7 receptors or removal of extracellular Ca^2＋ combined with blockade of inositol triphosphate receptors completely inhibited apoptosis or increase in cytoplasmic Ca^2＋. Removal of extracellular Ca^2＋ or blockade of inositol triphosphate receptor alone could partly inhibit these effects of isoflurane. Isoflurane could directly activate P2X7-gated channels and induce inward currents, but did not affect the expression of P2X7 receptor protein in neurons. These findings indicate that the mechanism by which isoflurane induced neuronal apoptosis in rat developing brain was mediated by intracellular calcium overload, which was caused by P2X7 receptor mediated calcium influx and inositol triphosphate receptor mediated calcium release.
文摘Using the specific affinity of tubulin for colchicine and the strong absorption of tubulin to DEAE ion exchangers at neutral pH and moderate ionic strength,the amounts of tubulin in the brain from both mice and chicks during different developing stages were measured by ~3H-colchicine assay (expressed as colchicine binding activity).The results show that the rate oftubulin synthesis reached a peak value during the critical period of brain development.This is exactly the period during which the organization and function of thyroid are being perfected.Besides,during breeding period,the difference of tubulin contents between male and female is significant(P<0.001).The synthesis of tubulin is strictly sex dependent(this phenomenon appeared only during sex maturation stage).It is suggested that sexual hormones might exert their effect on tubulin synthesis.
基金supported by the National Natural Science Foundation of China(32130035 and 92168107)STI2030-Major Projects(2021ZD0202500)+2 种基金the Frontier Key Project of the Chinese Academy of Sciences(QYZDJ-SSW-SMC025)Shanghai Municipal Science and Technology Projects(2018SHZDZX05)Shanghai Frontiers Science Center for Biomacromolecules and Precision Medicine at ShanghaiTech University.
文摘Understanding the fundamental processes of human brain development and diseases is of great importance for our health.However,existing research models such as non-human primate and mouse models remain limited due to their developmental discrepancies compared with humans.Over the past years,an emerging model,the“brain organoid”integrated from human pluripotent stem cells,has been developed to mimic developmental processes of the human brain and disease-associated phenotypes to some extent,making it possible to better understand the complex structures and functions of the human brain.In this review,we summarize recent advances in brain organoid technologies and their applications in brain development and diseases,including neurodevelopmental,neurodegenerative,psychiatric diseases,and brain tumors.Finally,we also discuss current limitations and the potential of brain organoids.
基金supported by the Hundred-Talent Program of Chinese Academy of Sciences(Y4065411411100050210)to J.L.+3 种基金the National Natural Science Foundation of China(8147131391649119)to J.L.the National Natural Science Foundation of China(31260242 to)F.Lthe National Science and Technology Infrastructure Program(2014BAI01B01-04)to S.L.
文摘Brain development and aging are associated with alterations in multiple epigenetic systems, including DNA methylation and demethylation patterns. Here, we observed that the levels of the 5- hydroxymethylcytosine （5hmC） ten-eleven transtocation （TET） enzyme-mediated active DNA demethylation products were dynamically changed and involved in postnatal brain development and aging in tree shrews （Tupaia belangeri chinensis）. The levels of 5hmC in multiple anatomic structures showed a gradual increase throughout postnatal development, whereas a significant decrease in 5hmC was found in several brain regions in aged tree shrews, including in the prefrontal cortex and hippocampus, but not the cerebellum. Active changes in Tet mRNA levels indicated that TET2 and TET3 predominantly contributed to the changes in 5hmC levels. Our findings provide new insight into the dynamic changes in 5hmC levels in tree shrew brains during postnatal development and aging processes.
基金supported primarily by the Spanish Ministry of Economy and Competitiveness((MINECO),DEP2017-91544-EXP)the Alicia Koplowitz Foundation+13 种基金supported by additional grants from MINECO(DEP2013-47540,DEP2016-79512-R,PID2020-120249RB-I00)the European Regional Development Fund(ERDF,FEDER in Spanish)the European Commission(No.667302)Further funding was obtained from the Andalusian Operational Programme supported by the ERDF(B-CTS-355-UGR18,B-CTS-500-UGR18 and A-CTS-614-UGR20)partially funded by the University of Granada,Plan Propio de Investigación 2016,Excellence actions:Units of ExcellenceUnit of Excellence on Exercise and Health(UCEES)and by the Regional Government of Andalusia,Regional Ministry of Knowledge,Science,and Universities and the ERDF(SOMM17/6107/UGR)supported by the School of Medicine,Complutense University of Madrid,Mother-Child Health and Development Network(Red SAMID)Ⅲnetwork,Redes temáticas de Investigación Cooperativa en Salud(RETICS),funded by the PN I+D+I 20172021(Spain)funded by the Ramón Areces Foundation.AMG is supported by FPU16/03653supported by the Spanish Ministry of Science and Innovation(RYC2019-027287-I)supported by a grant from Agencia Nacional de Investigación y Desarrollo(No.72180543)from Chilethrough a Margarita Salas grant from the Spanish Ministry Universitiessupported by MINECO and ERDF(grants RYC-2016-21199 and SAF2017-87526-R)the Junta de Andalucia(PAIDI P20_00158,PAIDI P20_00124)supported by the Spanish Ministry of Education,Culture and Sport(FPU 16/02760)。
文摘Background:Emerging research supports the idea that exercise positively affects neurodevelopment.However,the mechanisms linking exercise with brain health are largely unknown.We aimed to investigate the effect of exercise on(a)blood biomarkers selected based on previous evidence(brainderived neurotrophic factor,β-hydroxybutyrate(BHB),cathepsin B(CTSB),kynurenine,fibroblast growth factor 21(FGF21),soluble vascular cell adhesion molecule-1(sVCAM-1));and(b)a panel of 92 neurology-related proteins(discovery analysis).We also investigated whether changes in these biomarkers mediate the effects of exercise on brain health(hippocampal structure and function,cognitive performance,and mental health).Methods:We randomized 81 overweight/obese children(10.1±1.1 years,41%girls)into 2 groups:either 20 weeks of aerobic plus resistance exercise or control.Candidate biomarkers were assessed using enzyme-linked immunosorbent assay(ELISA)for kynurenine,FGF21,and CTSB;colorimetry forβ-hydroxybutyrate;and XMap for brain-derived neurotrophic factor and soluble vascular cell adhesion molecule-1.The92 neurology-related proteins were analyzed by an antibody-based proteomic analysis.Results:Our intervention had no significant effect on candidate biomarkers(all p>0.05).In the discovery analysis,a reduction in circulating macrophage scavenger receptor type-I was observed(standardized differences between groups=-0.3,p=0.001).This effect was validated using ELISA methods(standardized difference=-0.3,p=0.01).None of the biomarkers mediated the effects of exercise on brain health.Conclusions:Our study does not support a chronic effect of exercise on candidate biomarkers.We observed that while chronic exercise reduced the levels of macrophage scavenger receptor type-Ⅰ,it did not mediate the effects of exercise on brain health.Future studies should explore the implications of this novel biomarker for overall health.
基金The authors are supported by Universidade Federal do Rio Grande do Sul(UFRGS),Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq),Coordenação de Aperfeiçoamento de Pessoal de Nível Superior(CAPES),Fundação de AmparoàPesquisa do Estado do Rio Grande do Sul(FAPERGS),and Instituto Nacional de Ciência e Tecnologia para Excitotoxicidade e Neuroproteção(INCTEN/CNPq).
文摘Glial cells are crucial for maintaining central nervous system(CNS)homeostasis.They actively participate in immune responses,as well as form functional barriers,such as blood-brain barrier(BBB),which restrict the entry of pathogens and inflammatory mediators into the CNS.In general,viral infections during the gestational period can alter the embryonic and fetal environment,and the related inflammatory response may affect neurodevelopment and lead to behavioral dysfunction during later stage of life,as highlighted by our group for Zika virus infection.Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)induces a cytokine storm and,during pregnancy,may be related to a more severe form of the coronavirus disease-19(COVID-19)and also to higher preterm birth rates.SARS-CoV-2 can also affect the CNS by inducing neurochemical remodeling in neural cells,which can compromise neuronal plasticity and synaptic function.However,the impact of SARS-CoV-2 infection during pregnancy on postnatal CNS,including brain development during childhood and adulthood,remains undetermined.Our group has recently highlighted the impact of COVID-19 on the expression of molecular markers associated with neuropsychiatric disorders,which are strongly related to the inflammatory response.Thus,based on these relationships,we discussed the impact of SARS-CoV-2 infection either during pregnancy or in critical periods of neurodevelopment as a risk factor for neurological consequences in the offspring later in life,focusing on the potential role of glial cells.Thus,it is important to consider future and long-term public health concerns associated with SARS-CoV-2 infection during pregnancy.
基金This work was supported by the Natural Science Foundation of China （30470598）.
文摘Objective To study the developmental changes of glutamic acid decarboxylase-67 （ GAD-67, a GABA synthetic enzyme） in normal and hypoxic ischemic （HI） brain. Methods C57/BL6 mice on postnatal day （P） 5, 9, 21 and 60, corresponding developmentally to premature, term, juvenile and adult human brain were investigated by using both Western blot and immunohistochemistry methods either in normal condition or after hypoxic ischemic insult. Results The immunoreactivity of GAD67 was up regulated with brain development and significant difference was seen between mature （P21, P60） and immature （P5, P9） brain. GAD67 immunoreactivity decreased in the ipsilateral hemisphere in all the ages after hypoxia ischemia （HI） insult, but, significant decrease was only seen in the immature brain. Double labeling of GAD67 and cell death marker, TUNEL, in the cortex at 8h post-HI in the P9 mice showed that （15.6±7.0）% TUNEL positive cells were GAD67 positive which was higher than that of P60 mice. Conclusion These data suggest that GABAergic neurons in immature brain were more vulnerable to HI insult than that of mature brain.
文摘With the advent of modern techniques, drugs, and monitoring, general anesthesia has come to be considered an unlikely cause of harm, particularly for healthy patients. While this is largely true, newly emerging clinical and laboratory studies have sug- gested that exposure to anesthetic agents during early childhood may have long-lasting adverse effects on cognitive function. This concern has been the focus of intense study in the field of anesthesia research. A recent high-profile review by Rappaport et al. （2015） concluded that while many questions remain un- answered, there is strong evidence from laboratory studies that commonly used anesthetics interfere with brain development and that clinical studies suggest a correlation between early childhood exposure to these agents and subsequent effects on learning and cognition. The issue is of sufficient public health importance that a public-private partnership known as Smar- Tots （Strategies for Mitigating Anesthesia-Related Neurotoxicity in Tots） was developed by the FDA to study pediatric anesthetic neurotoxicity. The mechanism of injury underlying this phe- nomenon has yet to be fully elucidated, and there is evidence to suggest that anesthetics may have direct cytotoxic effects on neurons leading to cell death or suppressed neurogenesis （Strat- mann et al., 2010） and that they may interfere with key pro- cesses in neuronal growth and development that underlie brain circuit development （Wagner et al., 2014）.
基金supported by the National Key Research and Development Program of China(No.2018YFA0901103)the National Natural Science Foundation of China(No.21876196)。
文摘Tetrabromobisphenol A(TBBPA)is a widely used brominated flame retardant.There is evidence showing that TBBPA can exert thyroid disrupting effects in mammals,but different results were also reported,along with inconsistent reports regarding its neurotoxicity.Here,we investigated thyroid disrupting effects and neurotoxicity of TBBPA(5,50,500μg/(kg·day))to male mice following maternal and direct exposure through drinking water,with the antithyroid drug propylthiouracil(PTU)as the positive control.On postnatal day(PND)15,we expectedly observed severe thyroid compensatory hyperplasia and cerebellar developmental retardation in PTU-treated pups.The highest dose of TBBPA also caused thyroid histological alteration but had no effects on cerebellar development in terms of Purkinje cell morphology and the thickness of the internal granular layer and the molecular layer of the cerebellum.During puberty and adulthood,the thyroid morphological alterations became more pronounced in the TBBPA-treated animals,accompanied by decreased serum thyroid hormone levels.Furthermore,the 50 and 500μg/(kg·day)TBBPA groups showed a significant decrease in the serum level of serotonin,a neurotransmitter associated with anxiety behaviors.Correspondingly,the highest dose group displayed anxiety-like behaviors in the elevated plus-maze test on PND 35,but this neurobehavioral alteration disappeared on PND 56.Moreover,no changes in neurobehavioral parameters tested were found in TBBPAtreated animals at puberty and adulthood.Altogether,all observations show that TBBPA can exert thyroid disrupting effects but has little overt impact on brain development and neurobehaviors in mice,suggesting that thyroid disruption does not necessarily cause overtly adverse neurodevelopmental outcomes.
基金support from the Boettcher Foundation and the National Institutes of Health(1K99HD111686).
文摘Genomic mosaicism describes the phenomenon where some but not all cells within a tissue harbor unique genetic mutations.Traditionally,research focused on the impact of genomic mosaicism on clinical phenotype—motivated by its involvement in cancers and overgrowth syndromes.More recently,we increasingly shifted towards the plethora of neutral mosaic variants that can act as recorders of cellular lineage and environmental exposures.Here,we summarize the current state of the field of genomic mosaicism research with a special emphasis on our current understanding of this phenomenon in brain development and homeostasis.Although the field of genomic mosaicism has a rich history,technological advances in the last decade have changed our approaches and greatly improved our knowledge.We will provide current definitions and an overview of contemporary detection approaches for genomic mosaicism.Finally,we will discuss the impact and utility of genomic mosaicism.
基金Supported by the National Social Science Foundation,No.18BY0911.
文摘BACKGROUND Understanding the impact of early sensory deficits on brain development is essential for understanding developmental processes and developing potential interventions.While previous studies have looked into the impact of prenatal experiences on language development,there is a lack of research on how these experiences affect early language and brain function development in individuals with sensorineural hearing loss(SNHL).AIM To investigate SNHL effects on early brain development and connectivity in 4-month-olds vs healthy newborns and controls.METHODS The research involved analyzing the functional brain networks of 65 infants,categorized into three groups:28 healthy newborns,224-month-old participants with SNHL,and 15 age-matched healthy participants.The resting-state functional connectivity was measured and compared between the groups using functional near-infrared spectroscopy and graph theory to assess the brain network properties.RESULTS Significant differences were found in resting-state functional connectivity between participants with SNHL and age-matched controls,indicating a developmental lag in brain connectivity for those with SNHL.Surprisingly,SNHL participants showed better connectivity development compared to healthy newborns,with connectivity strengths of 0.13±0.04 for SNHL,0.16±0.08 for controls,and 0.098±0.04 for newborns.Graph theory analysis revealed enhanced global brain network properties for the SNHL group,suggesting higher communication efficiency at 4 months.No significant differences were noted in network properties between 4-month-old SNHL participants and neonates.A unique pattern of central hubs was observed in the SNHL group,with 2 hubs in the left hemisphere compared to 6 in controls.CONCLUSION 4-month-old infants with SNHL have a distinct brain network pattern with efficient long-distance information transmission but less effective local communication compared to age-matched controls.
文摘Microglia are the resident immune cells of the central nervous system （CNS）, In the normal state, microglia have a ramified shape and con- tinuously survey the conditions of the brain.
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).
