Developmental Neurobiology最新文献

{"title":"Syndromic Autism in Helsmoortel–Van der Aa Syndrome: From Clinical Suspicion to Genetic Diagnosis","authors":"Fethiye Kılıçaslan,&nbsp;Özlem Öz,&nbsp;Ceylan Carık,&nbsp;Mehmet Burak Mutlu,&nbsp;Abdullah İhsan Gürler","doi":"10.1002/dneu.70070","DOIUrl":"10.1002/dneu.70070","url":null,"abstract":"<div>\u0000 \u0000 <p>Syndromic autism refers to autism spectrum disorder (ASD) occurring as part of an identifiable genetic syndrome. Helsmoortel–Van der Aa syndrome (HVDAS/ADNP syndrome) is a rare autosomal dominant neurodevelopmental disorder caused by heterozygous pathogenic variants in the <i>ADNP</i> gene. We report a 10-year-old boy with ASD and intellectual disability who exhibited delayed motor and language development, characteristic facial dysmorphism, early tooth eruption, endocrine abnormalities, electroencephalography (EEG) abnormalities, and urogenital findings. Following unremarkable karyotyping and chromosomal microarray analysis (CMA), whole-exome sequencing identified a heterozygous pathogenic <i>de novo</i> frameshift variant, c.1239_1240del, <i>p</i>.(Gln414Valfs*25) in <i>ADNP</i>. This case emphasizes the importance of considering a syndromic etiology in children with ASD accompanied by developmental delay, dysmorphic features, neurological findings, or multisystem involvement, and supports comprehensive genetic evaluation when first-tier testing is unrevealing.</p>\u0000 </div>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"86 4","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179967","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":"Dexmedetomidine Activates AMPK/SIRT1 Pathway to Reduce Inflammatory Levels and Neuronal Pyroptosis to Alleviate Neonatal Hypoxic-Ischemic Brain Damage","authors":"Jinping Jiang,&nbsp;Ling Fan,&nbsp;Yejun Zhao,&nbsp;Yanwen Wang,&nbsp;Minzhi He,&nbsp;Weinong Mo,&nbsp;Jianhong Li,&nbsp;Mengzao He","doi":"10.1002/dneu.70067","DOIUrl":"10.1002/dneu.70067","url":null,"abstract":"<div>\u0000 \u0000 <p>Neonatal hypoxic-ischemic brain damage (HIBD) is the leading cause of neonatal death and long-term neurological dysfunction. Dexmedetomidine (DEX) has been shown to have neuroprotective effects, but its mechanisms in HIBD remain incompletely understood. This study aimed to explore whether DEX inhibits neuroinflammation and pyroptosis via activating adenosine monophosphate-activated protein kinase (AMPK)/sirtuin 1 (SIRT1) axis, thereby reducing HIBD. A HIBD model was established. Histological staining observed the pathological changes and neuronal survival. Primary cortical neurons were cultured to establish an oxygen–glucose deprivation/reoxygenation (OGD/R) model. DEX was used for intervene, and siAMPK was transfected to knock down AMPK expression. Inflammatory and oxidative stress indicators within brain tissue and neuronal cells were measured using enzyme-linked immunosorbent assay (ELISA) and biochemical kits. The AMPK/SIRT1 pathway and pyroptosis protein expressions were evaluated using fluorescence staining and Western blot. DEX dose-dependently reduced cerebral infarction volume, improved cerebral cortex pathological damage, enhanced neuronal nuclei (NeuN) positive neurons, decreased interleukin (IL)-6 and malondialdehyde (MDA) contents, enhanced superoxide dismutase (SOD) activity, and inhibited terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)/cleaved Caspase-1 double positive cells and N-terminal domain of Gasdermin D (GSDMD-N) protein expressions. DEX significantly upregulated p-AMPK and SIRT1 expression, whereas the AMPK inhibitor Compound C reversed the neuroprotective effect of DEX. In vitro experiments confirmed that DEX increased neuronal cell viability, reduced lactate dehydrogenase (LDH) release and propidium iodide (PI)-positive cell rate, reduced oxidative stress, and inhibited inflammatory factor release and pyroptosis-related protein expression. AMPK knockdown significantly reversed this axis activation by DEX and attenuated the neuroprotective effect of DEX. In conclusion, DEX improved neurological function in HIBD rats via the activating AMPK/SIRT1 pathway, reducing neuroinflammation and inhibiting neuronal pyroptosis.</p>\u0000 </div>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"86 4","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105435","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":"Microglial State Reprogramming Across the Gut–Brain–Immune Axis: Limitations and Therapeutic Prospects of Traditional Chinese Medicine","authors":"Muhammad Wasim Usmani,&nbsp;Muhammad Zulqarnain Shakir,&nbsp;Muneeb Ahmad Khan,&nbsp;Muhammad Usman,&nbsp;Inam Ullah,&nbsp;Yang Mengjie,&nbsp;Ning Wang,&nbsp;Xinmin Liu","doi":"10.1002/dneu.70060","DOIUrl":"10.1002/dneu.70060","url":null,"abstract":"<div>\u0000 \u0000 <p>Bidirectional communication among the gut microbiota, immune system, and central nervous system shapes microglial maturation and responsiveness. This review evaluates microglia as context-dependent neuroimmune integrators rather than fixed M1/M2 populations. It organizes the literature into three linked layers: gut-derived signals and barrier physiology, microglial state transitions, and therapeutic modulation by Traditional Chinese Medicine (TCM). Experimental depletion, colonization, and metabolite studies provide causal evidence that the microbiota can modify microglial biology in animals; however, human evidence remains predominantly associative. Herbal formulations, isolated constituents, and acupuncture may alter microbial ecology, intestinal permeability, metabolite production, systemic inflammation, and microglial signaling. Yet most intervention studies measure only selected links in this chain and rely on rodent behavior, bulk cytokines, or limited polarization markers rather than direct, state-resolved microglial profiling. Therefore, improvements in cognition or inflammatory markers cannot by themselves, establish microbiota-mediated microglial reprogramming. We critically distinguish direct from indirect evidence, replace binary polarization language with state-specific terminology, and evaluate formulation standardization, bioavailability, safety, experimental confounding, and clinical generalizability. A credible translational program will require chemically defined interventions, causal perturbation of candidate microbes or metabolites, microglia-resolved multi-omics, preregistered clinical trials, and mediation analyses that connect target engagement to patient-relevant outcomes. TCM is thus best regarded as a testable source of multicomponent interventions, not yet a validated systems-level therapy for the gut–brain–immune axis.</p>\u0000 </div>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"86 4","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149080176","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":"Age-Related Changes in E/I Balance Estimated With Hurst Exponent and Links With Developmental Skills in Preschool Children","authors":"Bosi Chen,&nbsp;Alexandra Boxberger,&nbsp;Judy Mahmalji,&nbsp;Giovanna Arantes de Oliveira Campos,&nbsp;Meagan Herrera,&nbsp;Annika Linke,&nbsp;Inna Fishman","doi":"10.1002/dneu.70068","DOIUrl":"10.1002/dneu.70068","url":null,"abstract":"<div>\u0000 \u0000 <p>Cortical excitation–inhibition (E/I) balance regulates sensitive periods of plasticity and is critical for brain development. Yet, neuroimaging studies characterizing E/I dynamics in early childhood are rare. The Hurst exponent (<i>H</i>), derived from resting-state functional magnetic resonance imaging (rs-fMRI), provides a noninvasive proxy for E/I balance. We investigated age-related changes in <i>H</i> using longitudinal rs-fMRI from 55 typically developing children aged 1.5–5 years (78 sessions during natural sleep). Linear mixed-effects models revealed significant age-related increases in <i>H</i>, signifying greater inhibition or more balanced E/I, in three right-hemisphere regions: inferior frontal gyrus (IFG) pars opercularis and triangularis, and middle temporal pole. Whole-brain maps showed positive age effects across most cortical areas, though the most robust increases occurred in higher order association cortices rather than primary sensory regions, consistent with hierarchical network maturation. Higher <i>H</i> in right IFG opercular was associated with better expressive language skills and fewer behavioral/emotional problems, controlling for age and sex. These findings suggest that E/I balance maturation during toddlerhood and preschool years is most pronounced in regions supporting language development and cognitive control. Our results characterized normative developmental trajectories of <i>H</i> during an important neurodevelopmental window and its associations with emerging behavioral competencies, potentially informing future investigations of atypical E/I maturation in neurodevelopmental disorders.</p>\u0000 </div>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"86 4","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149073878","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":"Integrated Mesh-Based Analysis of Neuronal Morphology, Synaptic Subcompartments, and Laminar Inputs in the H01 Human Temporal Cortex","authors":"Jiahe Jiao,&nbsp;Min Yang,&nbsp;Jiayu Chen,&nbsp;Shoubin Dong,&nbsp;Licheng Zhou,&nbsp;Yiping Liu,&nbsp;Zhenyu Jiang,&nbsp;Bao Yang,&nbsp;Zejia Liu,&nbsp;Liqun Tang","doi":"10.1002/dneu.70065","DOIUrl":"10.1002/dneu.70065","url":null,"abstract":"<div>\u0000 \u0000 <p>Quantitative nanoscale descriptions of human cortical neurons remain limited, particularly when neuronal morphology, synaptic geometry, and laminar input organization are examined within a unified connectomic framework. Using publicly available H01 human temporal cortex data and open-source tools, we developed a reproducible pipeline to decode sharded data, reconstruct neuronal and synaptic mesh models, and integrate mesh-based morphometry with annotation-derived laminar input analysis. The associated custom scripts will be released in a public repository upon publication. Morphometric analysis focused on a layer 5 pyramidal neuron, whereas laminar input profiles were examined in four layer 5 pyramidal neurons and four layer 5 interneurons. The reconstructed pyramidal neuron contained one soma, seven main limbs, and 207 branch-level skeleton segments, with a skeleton length of 10.13 mm and a soma volume of 9191.33 µm³. Branch parameters showed right-skewed heterogeneity, and branch length was strongly correlated with surface area (<i>r</i> = 0.864, <i>p</i> &lt; 0.001). Afferent synaptic subcompartments displayed irregular, flattened morphologies and continuous right-skewed bounding-box distributions without evidence of bimodality. Their volume and surface area were strongly correlated (<i>r</i> = 0.952, <i>p</i> &lt; 0.001), indicating coordinated geometric scaling. In the selected cohort, layer-wise input annotations were concentrated in layers III–V, with a layer V-dominant profile in the selected pyramidal neurons and broader distributions in the selected interneurons. Overall, this H01-based framework links neuronal morphology, synaptic-subcompartment geometry, and laminar input estimates, while broader conclusions require validation across additional neurons and donors.</p>\u0000 </div>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"86 4","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149073900","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":"Morus nigra L. Extract Mitigates Autistic-Like Behaviors in Maternally Separated Mice: Potential Involvement of Neuroinflammation, Nitric Oxide, and Oxidative Stress","authors":"Fariba Azadikhah,&nbsp;Hossein Amini-Khoei,&nbsp;Zahra Lorigooini,&nbsp;Seyedeh Maryam Kazemi,&nbsp;Elham Bijad,&nbsp;Hossein Tahmasebi Dehkordi,&nbsp;Mohammad Rahimi-Madiseh","doi":"10.1002/dneu.70066","DOIUrl":"10.1002/dneu.70066","url":null,"abstract":"<div>\u0000 \u0000 <p>Autism spectrum disorder (ASD) is a pervasive neurodevelopmental disorder with rising global prevalence and no effective pharmacological treatments. Early-life stress, such as maternal separation (MS), is a known risk factor that can lead to neuroinflammation and oxidative stress, contributing to autistic-like behaviors. This study addresses the knowledge gap by exploring the potential of <i>Morus nigra</i> L. (black mulberry) extract, known for its anti-inflammatory and antioxidant properties, in mitigating these behaviors in a mouse model of MS. In this study, 40 male NMRI mice were used. Hydroalcoholic extract of <i>M. nigra</i> was isolated by maceration method; then, it was administered to MS-exposed mice (20, 40, or 60 mg/kg), and its effects on social interaction, memory, aggression, and spatial learning were assessed by using behavioral tests, including a three-chamber test, resident-intruder test, shuttle box test, and Morris water maze test. Oxidative stress markers in the serum and hippocampus as well as gene expression of inflammatory mediators in the hippocampus were assessed. Behavioral tests revealed significant improvements in social preference and passive avoidance memory and reduced aggressive behaviors. The Morris Water Maze test indicated enhanced spatial learning and memory. Biochemically, <i>M. nigra</i> extract reduced malondialdehyde levels and nitrite levels and increased total antioxidant capacity in the hippocampus. Gene expression analysis showed decreased levels of pro-inflammatory cytokines, including <i>Tnf-α</i>, <i>Il-1β</i>, and <i>Tlr4</i>. These findings suggest that <i>M. nigra</i> extract mitigates autistic-like behaviors in MS mice by possibly attenuating neuroinflammation and oxidative stress, highlighting its potential for further investigation in ASD-related behavioral phenotypes. Further research is warranted to elucidate the precise mechanisms and optimize dosing strategies.</p>\u0000 </div>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"86 4","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149073884","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":"Molecular and Proteomic Profiling of Human Cerebral Organoid‑Derived Small Extracellular Vesicles","authors":"Elifsu Polatlı,&nbsp;Burak Kahveci,&nbsp;Çağla Kiser,&nbsp;Nurhan Özlü,&nbsp;Gökhan Karakülah,&nbsp;Şermin Genç,&nbsp;Sinan Güven","doi":"10.1002/dneu.70062","DOIUrl":"10.1002/dneu.70062","url":null,"abstract":"<p>Organoids are self-organized, in vitro 3D structures derived from progenitor or pluripotent stem cells. During culture, these tissues secrete small extracellular vesicles (sEVs)—functional bioactive molecules—into their microenvironment. Here, we differentiated iPSC-derived cerebral organoids (COs) under three culture conditions (static, orbital shaker, and a novel dynamic Organoid-on-a-Chip platform) over 30 days of maturation to determine how culture dynamics shape organoid development and EV profiles. Transcriptomic analysis revealed strong, culture condition-specific modulation of gene expression, while EV proteomics showed similar profiles across conditions at early maturation stages but marked divergence at later stages, reflecting differences in cellular maintenance, stress response, and tissue-specific maturation pathways. Additionally, sEVs from all conditions reduced U87 glioblastoma cell viability and migration, with the strongest effect observed for sEVs derived from the orbital shaker condition. These findings demonstrate that organoid culture microenvironment substantially influences both developmental trajectory and the bioactivity of secreted EVs.</p>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"86 4","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13644378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149073859","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":"Toward a Phase-Based Biological Stratification of Autism Spectrum Disorder: A Neuroinflammatory Developmental Framework","authors":"Rasha I. Gabr","doi":"10.1002/dneu.70063","DOIUrl":"10.1002/dneu.70063","url":null,"abstract":"<div>\u0000 \u0000 <p>Autism spectrum disorder (ASD) is a clinically and biologically heterogeneous neurodevelopmental condition arising from diverse genetic, epigenetic, and environmental influences. Increasing evidence suggests that immune dysregulation and sustained neuroinflammatory mechanisms contribute to the pathophysiology of a biologically defined subgroup of individuals with ASD. However, the temporal evolution of these processes and their relationship to clinical heterogeneity remain poorly understood. We propose a <i>phase-based neuroinflammatory developmental framework</i> in which systemic immune activation in genetically or epigenetically susceptible individuals initiates sustained activation of microglia and astrocytes, cytokine-mediated synaptic dysfunction, and altered neurodevelopmental trajectories. Within this framework, neuroinflammatory activity may precede or accompany developmental regression during an early active phase, followed by progressive synaptic dysfunction and persistent neurobiological sequelae. In later stages, individuals may continue to exhibit core autistic features despite reduced or absent detectable inflammatory biomarkers, providing a potential explanation for the inconsistent biomarker findings reported across the literature. Unlike previous hypotheses that primarily emphasized neuroinflammation as one contributor to ASD, the present framework introduces four conceptual advances: (i) a temporal phase-based model of disease evolution; (ii) a biologically informed stratification of a neuroinflammatory subgroup within ASD; (iii) a mechanistic explanation for temporal variability in inflammatory biomarker detection; and (iv) a series of testable predictions linking biological stage to clinical manifestations and therapeutic responsiveness. Supporting evidence derives from studies demonstrating persistent microglial and astrocytic activation, elevated inflammatory cytokines, synaptic abnormalities, immune dysregulation, developmental regression, and selected cases of autoimmune encephalitis presenting with autism-like phenotypes. Additional translational support arises from mechanistic overlap in neuroimmune signaling and preliminary therapeutic observations involving immunomodulatory and neuromodulatory interventions. The proposed framework generates specific, falsifiable predictions that can be examined using longitudinal biomarker studies, molecular neuroimaging, immune profiling, and stage-oriented clinical trials. If validated, this model could complement existing genetic and neurodevelopmental theories by supporting biological stratification of ASD, facilitating biomarker-guided patient selection, and informing individualized therapeutic strategies alongside established behavioral and rehabilitative interventions.</p>\u0000 </div>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"86 4","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029960","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":"Metformin Attenuates Behavioral Deficits and Oxidative Stress in a Preclinical Model of Autism","authors":"Madna Costa Freitas,&nbsp;Renê Felipe de Freitas,&nbsp;Iara Kessila Milhome Vasconcelos,&nbsp;Isadora Porto de Andrade,&nbsp;Maria Helena da Silva Pitombeira,&nbsp;David Ribeiro Fontenele,&nbsp;Pedro Otávio de Freitas Alves,&nbsp;Victoria Soares Diógenes,&nbsp;Ana Maria Sampaio Assreuy,&nbsp;Gislei Frota Aragão","doi":"10.1002/dneu.70061","DOIUrl":"10.1002/dneu.70061","url":null,"abstract":"<p>Autism spectrum disorder (ASD) is a complex neurodevelopmental condition lacking effective pharmacological treatments. Metformin has emerged as a candidate for drug repurposing in ASD due to its metabolic and neurobiological actions. This study evaluated the in vivo effects of metformin (400 mg/kg, orally) administered from postnatal day 21 to 35 (PND21–35) in male and female offspring of mice prenatally exposed to valproic acid (VPA; 450 mg/kg, i.p.) on gestational day 12.5 (GD12.5). Behavioral tests included the open field, elevated plus maze, Y-maze, three-chamber social interaction, and self-grooming. The prefrontal cortex (PFC) and hippocampus (HPC) were analyzed for oxidative stress markers (malondialdehyde [MDA], reduced glutathione [GSH]), total protein content, and acetylcholinesterase (AChE) activity. In vivo, metformin attenuated several VPA-associated behavioral alterations, including changes in locomotor/exploratory activity and repetitive behavior, with additional effects on anxiety-like behavior, sociability, and spatial working memory that varied according to sex and behavioral parameter. Biochemical analyses showed metformin-associated changes in GSH and MDA that varied across sexes and brain regions. VPA-induced increases in PFC AChE activity were attenuated by metformin in both sexes. Total protein content also varied according to sex and brain region. These findings provide preclinical evidence that metformin can attenuate behavioral alterations associated with prenatal VPA exposure and modulate oxidative stress-related markers, with patterns varying across sexes and brain regions.</p>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"86 4","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dneu.70061","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148988476","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":"Maternal and Postnatal Effects of Poly I:C-Induced Intrauterine Inflammation and Rytvela, a Non-Competitive IL-1R Antagonist, in the Pregnant Spiny Mouse","authors":"Nhi T. Tran,&nbsp;Rachid Kamareddine,&nbsp;Nadia Bellofiore,&nbsp;David M. Olson,&nbsp;Sylvain Chemtob,&nbsp;Sarah A. Robertson,&nbsp;Jeffrey A. Keelan,&nbsp;Stacey J. Ellery","doi":"10.1002/dneu.70064","DOIUrl":"10.1002/dneu.70064","url":null,"abstract":"<p>Maternal infection-induced inflammation during pregnancy is associated with adverse neurodevelopment. Rytvela, an allosteric IL-1 receptor antagonist, reduces IL-1β-mediated pathology in fetal rodents and sheep. However, its effects on TLR3-mediated inflammation and subsequent offspring growth and behavior remain unclear. Using precocial spiny mice, the primary outcome of this study was to examine whether rytvela could attenuate the acute maternal inflammatory response to mid-gestation exposure to polyinosinic:polycytidylic acid (Poly(I:C)). Secondary offspring outcomes included postnatal growth and behavior. At gestational day 20 (term = 39 days), pregnant mice received two intraperitoneal injections, 4 h apart, of saline (0.9% w/v, <i>n</i> = 14), Poly(I:C) (12 mg/kg, <i>n</i> = 14), or Poly(I:C) + rytvela (12 mg/kg + 3 mg/kg, respectively, <i>n</i> = 14). Ten dams/group were culled 8 h after dose 1 to assess inflammatory responses. The remainder (<i>n</i> = 4 dams/group) were delivered at term. Offspring (control <i>n</i> = 7, Poly(I:C) <i>n</i> = 8, Poly(I:C) + rytvela <i>n</i> = 11) growth was monitored and behavioral testing undertaken from postnatal day (PND) 3–45. Poly(I:C) increased maternal serum (<i>p</i> = 0.01) and amniotic fluid (<i>p</i> = 0.003) IL-1β, and upregulated <i>Il1b</i>, <i>Il6</i> and <i>Tnf</i> expression in the spleen and thymus. Rytvela reduced IL-1β levels but did not attenuate elevated cytokine gene expression. Poly(I:C) slowed postnatal growth (PND 18–27, <i>p</i> &lt; 0.05), which recovered earlier with rytvela. Poly(I:C) exposure did not alter offspring behavior in tests completed to PND 45. However, Poly(I:C) + rytvela offspring showed reduced locomotor activity (distance: <i>p</i> &lt; 0.001; velocity: <i>p</i> = 0.021). In conclusion, rytvela attenuated the primary inflammatory response to Poly(I:C), promoting earlier postnatal growth recovery despite persistent cytokine gene expression. Reduced locomotor activity after prenatal rytvela exposure warrants further investigation.</p>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"86 4","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dneu.70064","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148988473","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}