Developmental Neuroscience最新文献

{"title":"miR-26a Improves Microglial Activation and Neuronal Apoptosis in a Rat Model of Cerebral Infarction by Regulating the TREM1-TLR4/MyD88/NF-κB Axis.","authors":"Daxiong Xu, Qi'an Guo","doi":"10.1159/000533813","DOIUrl":"10.1159/000533813","url":null,"abstract":"<p><p>Emerging studies have indicated that abnormally expressed microRNAs (miRNAs) are related to the pathogenesis of cerebral ischemia. Nevertheless, the function of miR-26a in neuronal damage and microglial activation during cerebral infarction remains elusive. It was revealed that miR-26a was downregulated in oxygen-glucose deprivation (OGD)-treated microglia and neurons. Overexpressing miR-26a reduced the inflammatory reaction in BV2 cells and decreased neuronal apoptosis following OGD stimulation. miR-26a upregulation inactivated the TLR4/MyD88/NF-κB pathway and inhibited TREM1 expression. Repressing NF-κB phosphorylation inhibited the miR-26a level. As supported by the dual-luciferase reporter assay, TREM1 was directly targeted by miR-26a. Furthermore, a rat model of middle cerebral artery occlusion (MCAO) was built. We discovered that miR-26a improved cognitive, learning, and motor functions and reduced cerebral edema in MCAO rats. Mechanistically, upregulating miR-26a reduced inflammation and neuronal apoptosis by mitigating the TREM1-TLR4/MyD88/NF-κB pathway in the MCAO rat model. Collectively, this study verified that the miR-26a-TREM1-TLR4/MyD88/NF-κB axis contributes to modulating OGD-mediated microglial activation and neuronal injury.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"221-236"},"PeriodicalIF":2.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10228901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Central Autonomic Network and Heart Rate Variability in Premature Neonates.","authors":"Kelsey Christoffel, Josepheen De Asis-Cruz, Rathinaswamy B Govindan, Jung Hoon Kim, Kevin Michael Cook, Kushal Kapse, Nickie Andescavage, Sudeepta Basu, Emma Spoehr, Catherine Limperopoulos, Adre du Plessis","doi":"10.1159/000536513","DOIUrl":"10.1159/000536513","url":null,"abstract":"<p><strong>Introduction: </strong>The Central Autonomic Network (CAN) is a hierarchy of brain structures that collectively influence cardiac autonomic input, mediating the majority of brain-heart interactions, but has never been studied in premature neonates. In this study, we use heart rate variability (HRV), which has been described as the \"primary output\" of the CAN, and resting-state functional MRI (rsfMRI) to characterize brain-heart relationships in premature neonates.</p><p><strong>Methods: </strong>We studied premature neonates who underwent rsfMRI at term (37-week postmenstrual age or above) and had HRV data recorded during the same week of their MRI. HRV was derived from continuous electrocardiogram data during the week of the rsfMRI scan. For rsfMRI, a seed-based approach was used to define regions of interest (ROIs) pertinent to the CAN, and blood oxygen level-dependent signal was correlated between each ROI as a measure of functional connectivity. HRV was correlated with CAN connectivity (CANconn) for each region, and subgroup analysis was performed based on sex and clinical comorbidities.</p><p><strong>Results: </strong>Forty-seven premature neonates were included in this study, with a mean gestational age at birth of 28.1 +/- 2.6 weeks. Term CANconn was found to be significantly correlated with HRV in approximately one-fifth of CAN connections. Two distinct patterns emerged among these HRV-CANconn relationships. In the first, increased HRV was associated with stronger CANconn of limbic regions. In the second pattern, stronger CANconn at the precuneus was associated with impaired HRV maturation. These patterns were especially pronounced in male premature neonates.</p><p><strong>Conclusion: </strong>We report for the first time evidence of brain-heart relationships in premature neonates and an emerging CAN, most striking in male neonates, suggesting that the brain-heart axis may be more vulnerable in male premature neonates. Signatures in the heart rate may eventually become an important noninvasive tool to identify premature males at highest risk for neurodevelopmental impairment.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"373-385"},"PeriodicalIF":2.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11300706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139698817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxidative Stress Accompanies HIF1-Dependent Impairment of Glucose Metabolism in the Hippocampus of Adult Rats That Survived Prenatal Severe Hypoxia.","authors":"Oleg Vetrovoy, Viktor Stratilov, Sofiya Potapova, Ekaterina Tyulkova","doi":"10.1159/000535326","DOIUrl":"10.1159/000535326","url":null,"abstract":"<p><strong>Introduction: </strong>Many socially significant diseases are associated with prenatal developmental disorders. Previously, we showed the pathological role of hypoxia-inducible factor-1 (HIF1) in post-hypoxic reoxygenation. This study aimed to investigate the effect of prenatal severe hypoxia (PSH) on HIF1α protein expression as well as on HIF1-dependent activity of the pentose phosphate pathway (PPP) and anaerobic glycolysis in the hippocampus (HPC) of offspring that reached adulthood.</p><p><strong>Methods: </strong>PSH was induced during the critical period of fetal hippocampal formation on gestation days 14-16 in a hypobaric chamber (180 Torr, 5% oxygen, 3 h). Subsequent studies were conducted on both the HPC of adult control and PSH rats under normal conditions, as well as in response to severe hypoxia (SH) or psycho-emotional stress (\"learned helplessness\" [LH] model). We evaluated HIF1α protein levels using both immunohistochemistry and Western blotting techniques. The amount of glucose-6-phosphate dehydrogenase (G6PD) was also determined by Western blotting. Colorimetric enzymatic assays were employed to analyze enzymatic activity of lactate dehydrogenase (LDH), the concentration of lactate, NADPH, reduced glutathione (GSHred), and malonic dialdehyde (MDA).</p><p><strong>Results: </strong>We showed that PSH caused a stable increase in the content of HIF1α protein in the HPC, which was accompanied by an increase in the efficiency of anaerobic glycolysis. This was confirmed by increased LDH activity and lactate concentration. At the same time, the amounts of G6PD, NADPH, and GSHred decreased in the HPC of PSH rats, whereas the concentration of MDA, an oxidative stress marker, exceeded the control values. In a series of experiments using the LH or SH stress, it was shown that in the HPC of control rats, there was an increase in the amount of HIF1α in response to stress, which was also accompanied by more efficient anaerobic glycolysis and decrease of PPP-dependent NADPH production, similar to the intact PSH rats. In PSH rats, emotional stress resulted in higher HIF1α levels without affecting glycolysis or PPP.</p><p><strong>Conclusion: </strong>Therefore, the increased content and activity of the transcription factor HIF1α in the HPC of adult rats exposed to prenatal hypoxia leads to an imbalance between glycolysis and PPP, which is accompanied by oxidative stress.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"297-307"},"PeriodicalIF":2.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138048385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprotective Effects of Delayed TGF-β1 Receptor Antagonist Administration on Perinatal Hypoxic-Ischemic Brain Injury.","authors":"Hur Dolunay Kanal, Steven W Levison","doi":"10.1159/000531650","DOIUrl":"10.1159/000531650","url":null,"abstract":"<p><p>Hypoxic-ischemic (HI) brain injury in neonatal encephalopathy triggers a wave of neuroinflammatory events attributed to causing the progressive degeneration and functional deficits seen weeks after the primary damage. The cellular processes mediating this prolonged neurodegeneration in HI injury are not sufficiently understood. Consequently, current therapies are not fully protective. In a recent study, we found significant improvements in neurologic outcomes when a small molecule antagonist for activin-like kinase 5 (ALK5), a transforming growth factor beta (TGF-β) receptor was used as a therapeutic in a rat model of moderate term HI. Here, we have extended those studies to a mouse preterm pup model of HI. For these studies, postnatal day 7 CD1 mice of both sexes were exposed to 35-40 min of HI. Beginning 3 days later, SB505124, the ALK5 receptor antagonist, was administered systemically through intraperitoneal injections performed every 12 h for 5 days. When evaluated 23 days later, SB505124-treated mice had ∼2.5-fold more hippocampal area and ∼2-fold more thalamic tissue. Approximately 90% of the ipsilateral hemisphere (ILH) was preserved in the SB505124-treated HI mice compared to the vehicle-treated HI mice, where the ILH was ∼60% of its normal size. SB505124 also preserved the subcortical white matter. SB505124 treatment preserved levels of aquaporin-4 and n-cadherin, key proteins associated with blood-brain barrier function. Importantly, SB505124 administration improved sensorimotor function as assessed by a battery of behavioral tests. Altogether, these data lend additional support to the conclusion that SB505124 is a candidate neuroprotective molecule that could be an effective treatment for HI-related encephalopathy in moderately injured preterm infants.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"188-200"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9677286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New Insights into the Developmental Neurobiology of Brain Tumors.","authors":"Timothy N Phoenix","doi":"10.1159/000533817","DOIUrl":"10.1159/000533817","url":null,"abstract":"","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"147-148"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10673054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and Functional Study of Enhancers of EYA1: The Causative Gene of Branchio-Oto-Renal Syndrome.","authors":"Feng Wang, Ruizhi Zhang, Jing Jian, Yanhe Sun, Qiang Li","doi":"10.1159/000536260","DOIUrl":"10.1159/000536260","url":null,"abstract":"<p><strong>Introduction: </strong>Branchio-oto-renal syndrome (BOR syndrome) is a rare genetic disorder with an incidence of 1 in 40,000, affecting the development of multiple organs, including the branchio, ear, and kidney. It is responsible for 2% of childhood deafness. Currently, variants in the coding regions of the main causative genes, such as EYA1, SIX1, and SIX5, explain only half of the disease's etiology. Therefore, there is a need to explore the non-coding regions, which constitute the majority of the genome, especially the regulatory regions, as potential new causative factors.</p><p><strong>Method: </strong>In this study, we focused on the EYA1 gene, which accounts for over 40% of BOR syndrome cases, and conducted a screening of candidate enhancers within a 250-kb region upstream and downstream of the gene using comparative genomics. We characterized the enhancer activities of these candidates in zebrafish using the Tol2 transposon system.</p><p><strong>Results: </strong>Our findings revealed that out of the 11 conserved non-coding elements (CNEs) examined, four exhibited enhancer activity. Notably, CNE16.39 and CNE16.45 displayed tissue-specific enhancer activity in the ear. CNE16.39 required the full-length 206 bp sequence for inner-ear-specific expression, while the core functional region of CNE16.45 was identified as 136 bp. Confocal microscopy results demonstrated that both CNE16.39 and CNE16.45 drove the expression of GFP in the sensory region of the crista of the inner ear in zebrafish, consistent with the expression pattern of eya1.</p><p><strong>Conclusion: </strong>This study contributes to the understanding of the regulatory network governing EYA1 expression and offers new insights to further clarify the pathogenic role of EYA1 in BOR syndrome.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"333-340"},"PeriodicalIF":2.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139479568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Differentially Expressed MicroRNAs in the Rat Hippocampus during Adolescence through an Epigenome-Wide Analysis.","authors":"Ana Vázquez-Ágredos, Paula Rovira, Blanca Gutiérrez, Fernando Gámiz, Milagros Gallo","doi":"10.1159/000538168","DOIUrl":"10.1159/000538168","url":null,"abstract":"<p><strong>Introduction: </strong>Epigenetic mechanisms involving microRNAs (miRNAs) play a fundamental role in many biological processes, particularly during prenatal and early postnatal development. Their role in adolescent brain development, however, has been poorly described. The present study aimed to explore miRNA expression in the hippocampus during adolescence compared to adulthood in rats.</p><p><strong>Method: </strong>The brains of female and male Wistar rats were extracted, and the hippocampus was freshly dissected at postnatal day 41 (adolescence) and postnatal day 98 (adulthood). An epigenome-wide analysis was conducted to identify the miRNAs significantly expressed in adolescence compared to adulthood. Additionally, target genes of such miRNAs were considered to perform an exploratory Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis.</p><p><strong>Results: </strong>We identified 16 differentially expressed miRNAs in adolescent male rats compared with adult male rats and 4 differentially expressed miRNAs in adolescent females compared with adult females. Enrichment analysis reinforced that the target genes found are related to neurodevelopmental processes such as cell proliferation, cell migration, and nervous system development.</p><p><strong>Conclusion: </strong>Our findings suggest a complex pattern of miRNA expression during adolescence, which differs from that in adulthood. The differential expression of miRNA in the hippocampus during adolescence may be associated with the late developmental changes occurring in this brain region. Furthermore, the observed sex differences in miRNA expression patterns indicate potential sexual differentiation in hippocampal development. Further comprehensive investigations are needed to elucidate the roles of miRNA in normal brain development.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"401-410"},"PeriodicalIF":2.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11627067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140029498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum.","authors":"","doi":"10.1159/000534556","DOIUrl":"10.1159/000534556","url":null,"abstract":"","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"145"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50159188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preterm Birth by Cesarean Section: The Gut-Brain Axis, a Key Regulator of Brain Development.","authors":"Cécile Morin, Cindy Bokobza, Bobbi Fleiss, Elisa L Hill-Yardin, Juliette Van Steenwinckel, Pierre Gressens","doi":"10.1159/000534124","DOIUrl":"10.1159/000534124","url":null,"abstract":"<p><p>Understanding the long-term functional implications of gut microbial communities during the perinatal period is a bourgeoning area of research. Numerous studies have revealed the existence of a \"gut-brain axis\" and the impact of an alteration of gut microbiota composition in brain diseases. Recent research has highlighted how gut microbiota could affect brain development and behavior. Many factors in early life such as the mode of delivery or preterm birth could lead to disturbance in the assembly and maturation of gut microbiota. Notably, global rates of cesarean sections (C-sections) have increased in recent decades and remain important when considering premature delivery. Both preterm birth and C-sections are associated with an increased risk of neurodevelopmental disorders such as autism spectrum disorders, with neuroinflammation a major risk factor. In this review, we explore links between preterm birth by C-sections, gut microbiota alteration, and neuroinflammation. We also highlight C-sections as a risk factor for developmental disorders due to alterations in the microbiome.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"179-187"},"PeriodicalIF":2.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10278411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pediatric Glioma Models Provide Insights into Tumor Development and Future Therapeutic Strategies.","authors":"Amelia Foss, Manav Pathania","doi":"10.1159/000531040","DOIUrl":"10.1159/000531040","url":null,"abstract":"<p><p>In depth study of pediatric gliomas has been hampered due to difficulties in accessing patient tissue and a lack of clinically representative tumor models. Over the last decade, however, profiling of carefully curated cohorts of pediatric tumors has identified genetic drivers that molecularly segregate pediatric gliomas from adult gliomas. This information has inspired the development of a new set of powerful in vitro and in vivo tumor models that can aid in identifying pediatric-specific oncogenic mechanisms and tumor microenvironment interactions. Single-cell analyses of both human tumors and these newly developed models have revealed that pediatric gliomas arise from spatiotemporally discrete neural progenitor populations in which developmental programs have become dysregulated. Pediatric high-grade gliomas also harbor distinct sets of co-segregating genetic and epigenetic alterations, often accompanied by unique features within the tumor microenvironment. The development of these novel tools and data resources has led to insights into the biology and heterogeneity of these tumors, including identification of distinctive sets of driver mutations, developmentally restricted cells of origin, recognizable patterns of tumor progression, characteristic immune environments, and tumor hijacking of normal microenvironmental and neural programs. As concerted efforts have broadened our understanding of these tumors, new therapeutic vulnerabilities have been identified, and for the first time, promising new strategies are being evaluated in the preclinical and clinical settings. Even so, dedicated and sustained collaborative efforts are necessary to refine our knowledge and bring these new strategies into general clinical use. In this review, we will discuss the range of currently available glioma models, the way in which they have each contributed to recent developments in the field, their benefits and drawbacks for addressing specific research questions, and their future utility in advancing biological understanding and treatment of pediatric glioma.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"22-43"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9527225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}