Developmental Neuroscience最新文献

{"title":"Intranasal Inhibition of TrkB Signaling During Early Postnatal Development Disrupts Growth and Sensorimotor Maturation in Neonatal Rodents.","authors":"Serena-Kaye Sims, Aniston Hong, Marie Akirtava, Kennedy Camburn, Rishita Pawar, Caroline N Strickland, Emily Burke, Eli B Pfohl, Ma'Niya McKnight","doi":"10.1159/000552025","DOIUrl":"https://doi.org/10.1159/000552025","url":null,"abstract":"<p><strong>Introduction: </strong>Brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin receptor kinase B (TrkB), are critical regulators of neuronal growth, synaptic plasticity, and behavioral maturation during early development. The present study investigated how postnatal inhibition of TrkB signaling influences early neurobehavioral outcomes in neonatal rodents.</p><p><strong>Methods: </strong>Neonatal pups received daily intranasal administration of either saline or the TrkB antagonist ANA-12 (0.5 mg/kg or 1 mg/kg) on postnatal days (PND) 8 to 14 and were assessed for body weight gain, reflex development, and neuroinflammatory markers in cortical and hippocampal tissue.</p><p><strong>Results: </strong>ANA-12 treatment reduced body weight gain and delayed performance in righting, negative geotaxis, and cliff avoidance tasks. Total TrkB expression was significantly increased following ANA-12 treatment, while phosphorylated TrkB levels were unchanged, resulting in a reduction in the ratio of phosphorylated to total TrkB, an index of receptor activation. Inflammatory responses were region- and cytokine-specific, with significant reductions in hippocampal IL-6 and TNF-α, and a selective reduction in cortical TNF-α at the higher dose, while cortical IL-6 was not significantly altered.</p><p><strong>Conclusion: </strong>These findings indicate that TrkB inhibition during early development disrupts neurobehavioral maturation, alters receptor expression and activation balance, and modulates inflammatory signaling in a region-specific manner.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-18"},"PeriodicalIF":2.0,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147788090","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":"Long-Term Consequences of Preterm birth: A Lifespan Perspective.","authors":"Lina F Chalak, Natalie Vega Ortiz, Jennifer Joukhdar, Kara N Goss","doi":"10.1159/000551908","DOIUrl":"https://doi.org/10.1159/000551908","url":null,"abstract":"<p><strong>Background: </strong>Preterm birth is increasingly recognized as a determinant of health across the lifespan, influencing neurodevelopment, psychiatric risk, cardiovascular function, and mortality. This review synthesizes current evidence linking early-life adversity, including that associated with prematurity, to accelerated aging of to the brain-heart axis. We further describe the \"fetus to fifty\" model, highlighting how the early-life experiences of preterm-born infants impact adult trajectories across the lifespan.</p><p><strong>Summary: </strong>Cardiovascular and neurodevelopmental vulnerabilities in preterm-born infants are closely linked. Emerging evidence suggests that suboptimal perinatal hemodynamics and inflammation contribute to a shared cardio-cerebral phenotype, in which premature cardiovascular aging may impair cerebrovascular reserve and increase the risk of cognitive decline.</p><p><strong>Key messages: </strong>We review the fundamental physiology underlying the early origins of diseases relating to mental health, personality, psychiatric diagnosis, neuroanatomical changes, and cardiopulmonary outcomes, and aging, emphasizing the interplay between biological vulnerability and social determinants. Lastly, we identify gaps in knowledge and future research directions to better understand and mitigate premature aging in preterm-born adults.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-21"},"PeriodicalIF":2.0,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147788059","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":"Development of the gut microbiota throughout the first year of life and its association with socio-emotional development into childhood.","authors":"Mirjam Bloemendaal, Danique Mulder, Jip Gudden, Ineke Heikamp-de Jong, Athanasia Ioannou, Clara Belzer, Eugenia Emile Natasha, Sharmili Edwin Thanarajah, Anna-Katariina Aatsinki, Marleen M H J van Gelder, Alejandro Arias Vasquez","doi":"10.1159/000552189","DOIUrl":"https://doi.org/10.1159/000552189","url":null,"abstract":"<p><p>Introduction Early life is a critical window for the development of many bodily systems, including the gut microbiota and the central nervous system, that are inter-connected through the gut-brain-axis. These early life gut-brain-axis connections are often studied through cross-sectional cohorts, limiting insights into temporal developmental trajectories. This longitudinal cohort study assessed whether gut microbial development over the first year of life is associated with socio-emotional development into childhood. Methods The PRIDE (PRegnancy and Infant DEvelopment) BIOME study (n=81, n=42 males) is a focus cohort within the larger prospective PRIDE Study. Gut microbiome was measured 5 times throughout the first year of life (at 2, 4, 6, 9 and 12 months through V4 16S rRNA sequencing) and socio-emotional development 8 times over 4.5 years, between 6 months and 5 years through the Ages and Stages Questionnaire: Social-Emotional (ASQ-SE). We related the development of the gut microbiota of infants throughout their first year of life with their socio-emotional development into childhood, the latter modelled as a slope per individual (ASQ slope). We assessed effects of time, ASQ slope and its interaction with time on microbial community measures alpha and beta diversity, as well as taxonomy, using linear mixed-effects models and PERMANOVA, correcting for sex, birth weight, gestational age and sequencing depth. Results Expected developmental patterns on the gut microbiota over the first year of life were observed, including increased alpha diversity and clustering of beta diversity before and after solid food introduction. Interestingly, ASQ slope was a significant predictor of beta diversity (F(1,394)=25.90, p=0.001) and Bifidobacterium abundance across the first year of life (b= -0.745, SE= 0.24, pFDR= 0.023). Moreover, we observed a temporal association between ASQ slope and Eggerthella abundance (ASQ slope × timepoint interaction, b=0.709, SE=0.21, pFDR=0.009). That is, Eggerthella abundance decreased across the group, but not in \"late concern\" infants, with concern about socio-emotional development at more recent timepoints. Discussion This study shows that genera Bifidobacterium and Eggerthella, known to be altered in mental health conditions such as autism spectrum disorder and depression, are already linked to socio-emotional development during early life. Hence, this work contributes to the identification of gut microbial candidates relevant for preventive screening of healthy gut-brain development and microbiota-targeted interventions.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-27"},"PeriodicalIF":2.0,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147788069","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":"From Womb to Weaning: Microbial Signals That Shape the Developing Brain.","authors":"Hadar Neuman, Asif Shitrit, Sondra Turjeman, Omry Koren","doi":"10.1159/000551712","DOIUrl":"https://doi.org/10.1159/000551712","url":null,"abstract":"<p><p>The gut microbiota plays a vital role in shaping brain development through complex bidirectional communication within the microbiota-gut-brain axis. Emerging evidence highlights neural, immune, endocrine, metabolic, and epigenetic pathways by which gut microbes influence neurodevelopmental processes. This review synthesizes current knowledge on the temporal dynamics of gut colonization and brain maturation. Drawing on mechanistic insights from animal models, we emphasize the central role of the maternal microbiota and particularly, microbially derived metabolites that cross the feto-placental barrier and shape fetal brain development. We also discuss molecular and cellular targets of microbial influence, implications for neurodevelopmental disorders, and potential therapeutic strategies. Understanding these interactions opens new avenues for early-life interventions aimed at optimizing neurodevelopment and preventing neuropsychiatric conditions.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-16"},"PeriodicalIF":2.0,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147516386","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":"Adaptive Skills May Moderate the Association between Prenatal Stress Exposure and Limbic Brain Activation: A Developmental Functional Magnetic Resonance Imaging Study of Superstorm Sandy Exposure.","authors":"Donato Deingeniis, Monika Baldyga, Rung-Yu Tseng, Rebecca M Lee, Abid Fahim, Ishra Khan, Chikako Olsen, Veronica J Hinton, A Duke Shereen, Yoko Nomura","doi":"10.1159/000551574","DOIUrl":"10.1159/000551574","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;The developing brain shows remarkable capacity for adaptation following early adversity, but the behaviors that influence neural compensation mechanisms remain unclear. Prenatal stress exposure provides a natural model for studying these mechanisms, as it alters neurodevelopment while allowing examination of potential protective factors. However, whether early adaptive behaviors - the skills needed to meet everyday demands such as self-care and communication - can buffer against the neural consequences of prenatal stress has not been established. Natural disasters provide a unique opportunity to examine these mechanisms, as they serve as measurable prenatal stressors with well-defined exposure timing.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In this pilot study, using a quasi-experimental design, we examined children with (n = 11) and without (n = 23) prenatal exposure to Superstorm Sandy (SS) to investigate how early adaptive behavior (aged 2-6 years) moderates the association between prenatal stress (i.e., exposure to a natural disaster) and later brain activity during emotional processing (age 8 years). We first examined main effects of SS on both adaptive behaviors over time (aged 2-6 years) and functional brain activation at age 8 years in brain regions responsible for facial emotional processing. Moderation models subsequently explored whether early-life adaptive behaviors influenced the association between SS and later brain activation. The Behavior Assessment System for Children, Second Edition (BASC-2) measured child adaptive behaviors. Functional magnetic resonance imaging (fMRI) measured regional brain activation using an emotional face processing task.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Prenatal stress exposure was associated with nonsignificant trends toward reduced adaptive behaviors over time and reduced brain activation in the right ventral anterior insula. Critically, early adaptive behaviors moderated the association between prenatal stress and later brain activation in the left amygdala and both hemispheres of the hippocampus, ventral anterior insula, and rostral anterior cingulate cortex. Simple slope analyses revealed that prenatal stress was associated with significantly reduced brain activation at low adaptive skills. However, this association was attenuated among children that exhibited higher adaptive skills such that activation patterns were comparable to their unexposed peers.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Our preliminary moderation (i.e., interaction) findings provide initial evidence that adaptive behaviors may serve as a neural buffer against prenatal stress. This protective pattern indicates that early adaptive skills may help maintain neural responsiveness following prenatal stress exposure. If validated in larger, adequately powered samples, interventions targeting adaptive behaviors in early childhood could potentially reduce the neural burden of prenatal stress and support more resilie","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-14"},"PeriodicalIF":2.0,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13108944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147475556","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":"ARG1 Inhibition after Neonatal Hypoxic-Ischemic Brain Injury.","authors":"Eesha Natarajan, Jeffrey R Fineman, Donna M Ferriero, Emin Maltepe, Jana K Mike","doi":"10.1159/000551211","DOIUrl":"10.1159/000551211","url":null,"abstract":"<p><strong>Introduction: </strong>Neonatal hypoxic-ischemic (HI) brain injury is a major cause of mortality and long-term neurological disability, yet effective neuroprotective strategies remain limited. Microglia are central mediators of injury and repair, with arginase 1 (ARG1) marking anti-inflammatory, reparative states. However, the functional roles of ARG1+ microglia in tissue remodeling after HI are poorly understood.</p><p><strong>Methods: </strong>Neonatal mice (P10) underwent HI using the Vannucci procedure. ARG1 activity was inhibited pharmacologically using N-omega-hydroxy-nor-L-arginine (nor-NOHA). ARG1 expression, microglial morphology, efferocytosis, tissue scar, and injury volume were assessed via immunohistochemistry, Western blotting, and arginase activity assays at 1 and 5 days post-injury.</p><p><strong>Results: </strong>ARG1+ microglia rapidly engaged apoptotic neurons, exhibiting phagocytic activity confirmed by CD68 expression. Nor-NOHA treatment reduced ARG1 enzymatic activity, impaired microglial process extension, attenuated efferocytosis, and increased injury volume. ARG1+ microglia persisted in the glial scar and colocalized with collagen I alpha-1 (Col1a1), suggesting a role in extracellular matrix (ECM) deposition. Inhibition of ARG1 decreased Col1a1 expression, highlighting its contribution to tissue remodeling.</p><p><strong>Conclusions: </strong>ARG1+ microglia are pivotal in neonatal HI, mediating early efferocytosis and later ECM remodeling, thereby limiting injury and shaping scar architecture. Pharmacological blockade of ARG1 exacerbates injury, underscoring its reparative function. These findings establish ARG1 as a critical regulator of microglial-mediated neuroprotection and tissue repair, providing a potential therapeutic target for neonatal HI brain injury.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-11"},"PeriodicalIF":2.0,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13044354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147311772","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":"Modular Phosphoprotein Signatures Link Rac1 Inhibition to Neurite Morphogenesis in a Dose-Dependent Manner.","authors":"Yue Ge, Danielle Freeborn, Maliha S Nash, Prasada Rao S Kodavanti, Timothy J Shafer, Cina M Mack, David W Herr","doi":"10.1159/000550889","DOIUrl":"10.1159/000550889","url":null,"abstract":"<p><strong>Introduction: </strong>Precise regulation of neurite initiation, elongation, and branching is critical for neuronal network formation. Rac1, a key regulator of cytoskeletal remodeling, influences neurite morphogenesis through protein phosphorylation-mediated signaling, but the global phosphorylation landscape that governs Rac1-mediated morphogenesis remains unknown.</p><p><strong>Method: </strong>To address this knowledge gap, we performed phosphoproteomics profiling of primary rat cortical neurons treated with 3, 10, or 30 µ<sc>m</sc> of a Rac1 inhibitor for 48 h to evaluate phosphoprotein dynamics. Phosphorylation levels of 167 signaling proteins were quantified using a targeted phospho-antibody array and correlated with neuron count, neurite count and length, and branch point count.</p><p><strong>Results: </strong>Correlation analysis identified morphology-specific phosphoproteins, such as Tau (Thr181), GluR1 (Ser863), TrkB (Tyr515), and Merlin (Ser10), whose phosphorylation levels were significantly altered across three Rac1 inhibitor concentrations, and multiple phosphorylation sites showed dose-specific correlations with neurite morphology features.</p><p><strong>Conclusion: </strong>These results define a correlation-based framework linking phosphoprotein signaling to neurite morphology and offer novel insights into neurodevelopmental processes, neuronal disorders, and developmental neurotoxicity.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-15"},"PeriodicalIF":2.0,"publicationDate":"2026-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13048724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146208125","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":"Modest Neurodevelopment Impacts of <italic>APOE4</italic> in a Human Brain Organoid Model of Low-Grade SARS-CoV-2 Infection.","authors":"Aranis Muniz-Perez, Karina K Meyer-Acosta, Samhitha Boyana, Varsha Ponnala, Courtney Lee McMahon, Adyasha Aruk, Amber Elizalde, Jenny Hsieh","doi":"10.1159/000550957","DOIUrl":"10.1159/000550957","url":null,"abstract":"<p><strong>Introduction: </strong>The long-term neurological consequences of SARS-CoV-2, the virus responsible for the COVID-19 pandemic, are an area of growing concern, particularly for prenatally exposed individuals. Prior research has shown that APOE4, the leading genetic risk factor for late-onset Alzheimer's disease, is associated with increased COVID-19 severity and enhanced SARS-CoV-2 neurotropism. However, whether the interaction between APOE4 and SARS-CoV-2 infection leads to adverse neurodevelopmental outcomes remains unclear. Using human induced pluripotent stem cell-derived cortical and ganglionic eminence organoids (COs and GEOs) to model neurodevelopment, we have previously reported that SARS-CoV-2 preferentially infects glial cells, and that APOE4 promotes gliogenesis in COs and accelerates GABAergic neuron differentiation in GEOs. Here, we build upon our previous work by using COs and GEOs to examine how APOE4 modifies cellular responses to SARS-CoV-2 during late gestational development.</p><p><strong>Methods: </strong>Using low viral titers to better mimic natural infection, COs and GEOs were infected at 220-270 days in vitro, aligning with the third trimester, and were analyzed 7 days post infection.</p><p><strong>Results: </strong>We observed region-specific, APOE4-dependent changes. In infected COs, APOE4 elevated immature astrocyte marker, suggesting a genotype-dependent glial response. Additionally, infected GEOs exhibited reduced marker expression for mature neurons within both genotypes. Notably, APOE4 and SARS-CoV-2 interacted to modulate immature neuron expression in a region-specific manner.</p><p><strong>Conclusion: </strong>Taken together, this study suggests that APOE4 modulates region-specific responses to low-grade SARS-CoV-2 infection, underscoring the importance of exploring how genetic risk factors alter neurodevelopmental vulnerability to prenatal viral infection.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-10"},"PeriodicalIF":2.0,"publicationDate":"2026-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12998116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146208130","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":"Ultrarare Variants in DNA Damage Repair and Mitochondrial Genes in Pediatric Acute-Onset Neuropsychiatric Syndrome and Acute Behavioral Regression in Neurodevelopmental Disorders.","authors":"Dhanya Vettiatil, Anjana Soorajkumar, Robert A Dubin, Erika M Pedrosa, Allan Schornagel, John S Lambert, Isadora Pinheiro Costa, Joseph McDonald, Sigrid M A Swagemakers, Peter J van der Spek, Jennifer Frankovich, Janet L Cunningham, Herbert M Lachman","doi":"10.1159/000550301","DOIUrl":"10.1159/000550301","url":null,"abstract":"<p><strong>Introduction: </strong>We recently identified variants in 10 genes that are members of either the p53 pathway or Fanconi Anemia Complex (FAC), regulators of DNA repair (DNA damage response [DDR]) in 17 cases with pediatric acute-onset neuropsychiatric syndrome (PANS) or regression in autism spectrum disorder and other neurodevelopmental disorders (NDD). We aimed to identify additional cases with genetic vulnerabilities in DDR and related pathways.</p><p><strong>Methods: </strong>Whole-exome sequencing (WES) and whole-genome sequencing (WGS) data from 32 individuals were filtered and analyzed to identify ultrarare pathogenic or likely pathogenic variants.</p><p><strong>Results: </strong>Variants affecting DDR were found in 14 cases diagnosed with PANS or regression (CUX1, USP45, PARP14, UVSSA, EP300, TREX1, SAMHD1, STK19, MYTl1, TEP1, PIDD1, ADNP, FANCD2, and RAD54L). The CUX1 variant is de novo, as are two cases that had mutations in genes that affect mitochondrial functions that are connected directly or indirectly to mitophagy (PRKN and POLG), which can trigger the same innate immune pathways when disrupted as abnormal DDR. We also found pathogenic or likely pathogenic secondary mutations in several genes that are primarily expressed in the gut that have been implicated in gut microbiome homeostasis (e.g., LGALS4, DUOX2, CCR9).</p><p><strong>Conclusion: </strong>These findings align with previous genetic findings and strengthen the hypothesis that abnormal DDR and mitochondrial dysfunction underlie pathogenic processes in at least some cases of neuropsychiatric decompensation. The potential involvement of genetic variants in gut microbiome homeostasis is a novel aspect of our study. Functional characterization of the downstream impact of DDR deficits may point to novel treatment strategies.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-19"},"PeriodicalIF":2.0,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13008398/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146151212","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":"Effect of Limited Bedding and Nesting in Early Ontogenesis on Gene Expression in the Hippocampus and Frontal Cortex of Adolescent Rats Subjected to Restraint.","authors":"Angelina K Deryabina, Alexey A Kvichanskiy, Mikhail V Onufriev, Yulia V Moiseeva, Olga A Nedogreeva, Alexey P Bolshakov, Mikhail Y Stepanichev, Natalia V Gulyaeva","doi":"10.1159/000550785","DOIUrl":"10.1159/000550785","url":null,"abstract":"<p><strong>Introduction: </strong>According to literature, early stress may lead to a higher susceptibility to the action of various stressors later in life, thus largely contributing to the development of a wide range of affective disorders. Disrupting maternal care is one way to destabilize the environment for pups, which may result in the formation of an altered reaction to acute or moderate stress.</p><p><strong>Methods: </strong>In this study, we analyzed the effects of limited bedding and nesting material (LBN) in PND2-PND9 on baseline gene expression in the hippocampus and frontal cortex of 1-month-old rats and the expression of the same genes under conditions of 60-min restraint. Among the analyzed genes, some were associated with glucocorticoids (Nr3c1 and Nr3c2), others with the activation of the immune system (Nfkbia, Ccl2, Il1b, Il6, Tnfα, Cx3cl1, Cx3cr1, and Ncf1), and yet others with the activation of neuronal networks under stress (Cfos, Ier-2). Gene expression was assessed using real-time PCR.</p><p><strong>Results: </strong>Exposure to LBN during early postnatal life significantly increased baseline expression of the Fos gene in the amygdala of adolescent rats. LBN exposure more slightly affected the expression of other analyzed genes (Nr3c1, Cx3cl1, Ier2, Ncf1) or evoked alterations of their expression in this group only after exposure to acute restraint stress. The hyperglycemic response to acute restraint was attenuated in LBN-exposed animals, while corticosterone levels were comparable to controls. Among the studied genes, the expression of Nfkbia, Il6, and Tnf was primarily influenced by acute restraint stress, independently of LBN history. The amygdala and ventral hippocampus were the brain regions where the expression of the analyzed genes appeared most sensitive to the experimental manipulations.</p><p><strong>Conclusion: </strong>These data indicate that early-life stress induced by LBN leads to a sustained increase in baseline Fos expression in the amygdala and alters the metabolic response to acute stress in adolescence. The findings further suggest that the amygdala and ventral hippocampus are key regions where the expression of a limited set of stress-related genes is modulated by the interplay of early-life adversity and acute stress. These points to a potential role for amygdalar circuits in the altered stress reactivity observed following adverse early-life conditions.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-15"},"PeriodicalIF":2.0,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146094880","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}