Developmental Neurobiology最新文献

{"title":"Prenatal Indomethacin Exposure Is Associated With Autism-Relevant Behavioral Alterations Linked to Oxidative Stress and Altered Autophagy-Related Signaling.","authors":"Bakiye Akbaş, Ahmet Akbaş, Nadir Adnan Hacım, Gülçin Ercan, Hatice Aygün, Mümin Alper Erdoğan, Yiğit Uyanıkgil, Oytun Erbaş","doi":"10.1002/dneu.70041","DOIUrl":"10.1002/dneu.70041","url":null,"abstract":"<p><p>Autism spectrum disorder (ASD) arises from interactions between genetic predisposition and prenatal environmental insults. Prostaglandin E₂ (PGE₂), derived from cyclooxygenase-2 (COX-2), regulates neuronal differentiation and glia-neuron signaling; thus, its inhibition during gestation may impair neurodevelopment. To examine whether prenatal exposure to indomethacin, a non-selective COX inhibitor, induces autism-like alterations in rats with possible sex differences. Sixteen pregnant Wistar rats received indomethacin (1 mg/kg, gavage) on Gestational Days 10-14. Adult offspring (P50-P54) underwent behavioral tests (open-field, rearing, rotarod, and three-chamber sociability). Hippocampal and cerebellar tissues were analyzed for PGE₂, LC3B (ELISA), MDA (TBARS), neuronal density, and GFAP expression (CA1, CA3 - Nissl, GFAP staining). Indomethacin reduced sociability, exploration, and motor performance, especially in males, and decreased PGE₂ and LC3B while increasing MDA (p < 0.001). Histologically, CA1 neuronal counts increased while GFAP immunoreactivity was markedly elevated in hippocampal (CA1 and CA3) and cerebellar regions (p < 0.05), reflecting astroglial activation and neuroinflammatory remodeling. Prenatal inhibition of prostaglandin synthesis may disturb PGE₂ signaling, leading to oxidative stress, altered autophagy-related signaling, and glial activation, which together contribute to ASD-relevant behavioral outcomes.</p>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"86 3","pages":"e70041"},"PeriodicalIF":2.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147940678","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":"Vagus Nerve Stimulation Paired With Tones Alters the Auditory Cortex Proteome in a Rat Model of Rett Syndrome.","authors":"Isabella K Myers, Fang Bian, Maria P Solano, Yara El Zoghby, Diana Tavares-Ferreira, Tanya Danaphongse, Crystal T Engineer","doi":"10.1002/dneu.70032","DOIUrl":"10.1002/dneu.70032","url":null,"abstract":"<p><p>Rett syndrome is a neurodevelopmental disorder caused by an X-linked mutation of the MeCP2 gene. Individuals with Rett syndrome, as well as rodent models of this disorder, demonstrate abnormal cortical responses to sound, which impair auditory discrimination ability. Vagus nerve stimulation (VNS) paired with tones has been shown to drive robust changes in the auditory cortex physiology of Mecp2^+/- rats and has the potential to improve the communication abilities of individuals with Rett syndrome. The aim of this study was to describe the proteomic differences present in the auditory cortex of the Mecp2^+/- rat model of Rett syndrome, as well as the molecular effect of VNS paired with tones. This study used global proteomic analysis of auditory cortex tissue taken from Mecp2^+/- rats exposed to VNS paired with tones compared to untreated Mecp2^+/- rats and wild-type (WT) littermate controls with no VNS exposure. Our results demonstrate dysregulation of mitochondrial and synaptic proteins in the Mecp2^+/- rat auditory cortex. In addition, we show that VNS-tone pairing induces significant alterations to the auditory cortex proteome of Mecp2^+/- rats by changing the expression of proteins involved in regulating synaptic vesicles and synaptic transmission. This work provides evidence of key mechanisms that may drive auditory processing dysfunction in Rett syndrome and demonstrates that VNS-tone pairing is sufficient to alter protein expression in the auditory cortex.</p>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"86 3","pages":"e70032"},"PeriodicalIF":2.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13133546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147812169","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":"Clinical and Genetic Insights Into Aymé-Gripp Syndrome: Two Unrelated Cases With Additional Clinical Findings and Paternal Mosaicism.","authors":"Kubra Ates","doi":"10.1002/dneu.70044","DOIUrl":"10.1002/dneu.70044","url":null,"abstract":"<p><p>Aymé-Gripp syndrome is an ultra-rare autosomal dominant multisystem disorder caused by pathogenic variants in the MAF gene, typically affecting the N-terminal transactivation domain. It is characterized by craniofacial dysmorphism, early-onset cataracts, sensorineural hearing loss, developmental delay or intellectual disability, and variable neurological or skeletal anomalies. Here, we report two unrelated Turkish patients harboring heterozygous MAF variants within the glycogen synthase kinase 3 recognition motif, evaluated using clinical, neuroimaging, and molecular approaches. Targeted next-generation sequencing (NGS) and parental segregation analyses by NGS and Sanger sequencing were performed, and a literature review of cases published between January 2015 and April 2026 was conducted. Both patients presented with craniofacial and neurodevelopmental features. However, one patient showed no clinically detectable ocular abnormalities or hearing impairment at the time of evaluation. The detected variant in this patient was inherited from his asymptomatic father with low-level mosaicism (16% variant allele frequency in blood and 22% in buccal mucosa), representing the first reported case suggestive of paternal germline mosaicism in Aymé-Gripp syndrome. Literature review (n = 38) revealed consistent findings of sensorineural hearing loss (94.5%), cataracts (78.3%), developmental delay/intellectual disability (100%), epilepsy (68.5%), skeletal anomalies (72.7%), and cardiac involvement (55.1%). Additional features, including non-cataract ocular abnormalities, renal involvement, dermatologic findings, and hematological manifestations, have also been reported. All variants clustered within residues 54-69 of the transactivation domain. These findings provide clinically and molecularly relevant insights into Aymé-Gripp syndrome and highlight the importance of molecular diagnosis and the detection of parental mosaicism for accurate recurrence risk assessment and genetic counseling.</p>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"86 3","pages":"e70044"},"PeriodicalIF":2.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148041548","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":"The Memorization Process and Learning Abilities of School Children in Morocco.","authors":"Soukaina Loulidi, Youssef El Bahi, Ismail Chaaouf, Mohamed Loukid, Samia Boussaa","doi":"10.1002/dneu.70037","DOIUrl":"10.1002/dneu.70037","url":null,"abstract":"<p><p>Neurocognitive functions play a fundamental role in children's learning and academic success. Among these functions, memorization-based on associative cognitive processes-is essential for knowledge acquisition. In Morocco, educational disparities between rural and urban environments and differences between public and private schools may influence cognitive development and learning outcomes among schoolchildren. This study aimed to analyze the memorization process among Moroccan school-aged children and to identify demographic and contextual factors associated with learning performance. A cross-sectional study was conducted among 441 children aged 8-15 years recruited from six public and private schools in the Marrakech-Safi region of Morocco between November 2022 and March 2023. Memorization and learning abilities were assessed using the adapted Moroccan version of the Rey-Taylor auditory-verbal learning test (AVLT). Key indicators included the total number of recalled words across 10 trials, the learning index, and retroactive interference. Associations between cognitive performance and contextual variables (age, gender, school type, and residence) were analyzed using Spearman correlation tests. The results show that the learning index is relatively higher among girls (M = 4.8, standard deviation [SD] = 2.70), children over 12 years old (M = 5.0, SD = 2.39), children from rural areas (M = 5.0, SD = 2.62), and those enrolled in the public sector (M = 5.0, SD = 2.59), compared with other categories. These variables were the least affected by retroactive interference except for the rural environment, which experienced an RI = 68.8, SD = 0.21. However, the data indicate a performance among private-sector and younger students in at least one learning assessment stage. The Spearman test showed a positive correlation between the learning index and the age variable (r = 0.095; p = 0.046), and between retroactive interference and the living environment (r = 0.105; p = 0.028) and the type of school (r = 0.126; p = 0.0008). Overall, improving memory and academic performance requires targeted pedagogy, extracurricular activities, equal school opportunities, and research on factors, such as motivation, social dynamics, and teaching methods. Similarly, longitudinal studies will help deepen the understanding of memory and guide educational policies.</p>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"86 3","pages":"e70037"},"PeriodicalIF":2.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147940727","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":"Regulators of Wnt Signaling Dkk-1 and Notum Are Elevated in Pediatric ADHD.","authors":"Fatma Coşkun, Ayşegül Metin Emre, İbrahim Kılınç, Ahmet Osman Kılıç","doi":"10.1002/dneu.70042","DOIUrl":"10.1002/dneu.70042","url":null,"abstract":"<p><p>Wnt signaling has increasingly drawn attention in discussions of ADHD, yet the peripheral status of its upstream regulators remains largely uncharted. In this study, we examined circulating levels of four key modulators of this pathway-Dkk-1, PORCN, Notum, and Tiki-1-in a sample of children and adolescents with an ADHD diagnosis. A total of 158 children and adolescents, comprising 82 with ADHD and 76 healthy controls aged 8-18 years, were enrolled. ADHD diagnoses were established according to DSM-5 criteria utilizing the K-SADS-PL questionnaire. The severity of ADHD symptoms was assessed using scores from the Turgay DSM-IV-Based Screening and Evaluation Scale for Attention Deficit and Disruptive Behavior Disorders-Parent Form (T-DSM-IV-S). Serum levels of Dkk-1, PORCN, Notum, and Tiki-1 were quantified using ELISA kits. Children with ADHD demonstrated markedly increased serum concentrations of Dkk-1 and Notum relative to controls (p < 0.01). Elevated PORCN levels were also observed; however, this finding should be interpreted with caution (p < 0.01). Tiki-1 levels showed no significant difference between the groups. No substantial relationships were detected between serum concentrations of the studied analytes and the severity of ADHD symptoms. The significance of these findings was maintained after adjustment for age and sex. This study extends the literature by examining peripheral concentrations of Dkk-1, PORCN, Notum, and Tiki-1 in ADHD. The elevated levels of Dkk-1 and Notum may reflect alterations in Wnt-related signaling pathways, while the interpretation of PORCN findings remains limited. Taken together, these findings indicate peripheral molecular differences associated with ADHD and provide a basis for future research investigating Wnt-related signaling pathways in ADHD. However, these results should be interpreted as exploratory findings requiring further validation using complementary analytical approaches.</p>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"86 3","pages":"e70042"},"PeriodicalIF":2.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148040890","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":"Zika Virus Inoculation During Pregnancy Impaired Maternal Care and Altered Prolactin and Corticosterone Levels in Rats.","authors":"Meirylanne Gomes-da-Costa, Adriana Souza Dos Santos, Anna Luísa Lothhammer Bohn, Bruna Carolina de Castro Saturnino, Gabrielle Batista de Aguiar, Gabriela Barth Jacobs, Chris Krebs Danilevicz, Ana Paula Muterle Varela, Thais Fumaco Teixeira, Paulo Michel Roehe, Lenir Orlandi Pereira","doi":"10.1002/dneu.70053","DOIUrl":"10.1002/dneu.70053","url":null,"abstract":"<p><p>Zika virus (ZIKV) is an Orthoflavivirus known for its teratogenicity and for causing congenital Zika syndrome (CZS) in the offspring, but recent studies suggest a negative impact on maternal brain health and behavior following gestational ZIKV inoculation. This behavior, crucial for the offspring's neurodevelopment, is regulated by the hypothalamic-pituitary-adrenal (HPA) axis and prolactin. This study investigated the effect of gestational ZIKV inoculation on maternal care in Wistar rats and its relationship with prolactin and corticosterone levels. Fifty-six females were inoculated intraperitoneally on gestational day 9 (G9) with ZIKV (28 ZK group) or vehicle (28 CT group). Blood and hypothalamus samples from a set of these animals (n = 16/group) were collected 24 h postpartum to quantify corticosterone and prolactin levels by ELISA. Maternal behavior was evaluated on postnatal days 4 and 8 (n = 12/group). ZK rats demonstrated impaired maternal care compared to CT rats. Furthermore, 24 h postpartum, ZK rats had significantly lower levels of serum and hypothalamic corticosterone, and serum prolactin. The findings suggest that gestational ZIKV inoculation compromises maternal behavior in Wistar rats, concomitant with an alteration in the hormonal profile in the immediate postpartum period. The study is pioneering in demonstrating that ZIKV affects crucial components for the regulation of maternal behavior, reinforcing the need for further research to elucidate the mechanism in the maternal brain and develop targeted therapies.</p>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"86 3","pages":"e70053"},"PeriodicalIF":2.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13352443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148419599","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":"Roles of POU3F2 in Brain Development and Neuropsychiatric Disorders.","authors":"Xueqin Liu, Huihua Xu, Yunhe Zhao, Jing Yang, Li Zhang, Zengtian Wang, Kahleong Lim, Chengwu Zhang, Li Lu","doi":"10.1002/dneu.70034","DOIUrl":"10.1002/dneu.70034","url":null,"abstract":"<p><p>POU3F2, a member of the Pit-Oct-Unc (POU) domain transcription factor family, is widely expressed in the central nervous system and essential for the development and maturation of brain. POU3F2 deletion results in impaired hypothalamus and neocortex development, and most mice die between postnatal days 0 and 10. Recently, emerging evidences have demonstrated that POU3F2 is involved in neuropsychiatric disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, bipolar disorder, schizophrenia, and autism spectrum disorder, albeit still with some limitations in current studies. Besides, POU3F2 also plays a vital role in the reprogramming of somatic cells into neuronal lineages, which provides new ideas and directions for the treatment of neuropsychiatric disorders. This review aims to systematically summarize and analyze the diverse roles of POU3F2 in brain development, neuropsychiatric disorders, and neuronal reprogramming. Furthermore, the potential of POU3F2-targeted therapies for neuropsychiatric disorders and proposed key questions for future research are also emphasized. POU3F2 plays a pivotal role in brain development, the pathogenesis of neurological and psychiatric disorders, and the reprogramming of neural cells. A more comprehensive and systematic understanding of its molecular mechanism might provide novel therapeutic approaches for neuropsychiatric disorders.</p>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"86 3","pages":"e70034"},"PeriodicalIF":2.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834976","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":"TERT Promotes Reactive Astrocytes Proliferation and Differentiation Through the Wnt/β-Catenin Pathway and Improves Spinal Cord Injury.","authors":"Shutao Gao, Shizhe Li, Yukun Hu, Weibin Sheng","doi":"10.1002/dneu.70040","DOIUrl":"10.1002/dneu.70040","url":null,"abstract":"<p><p>Spinal cord injury (SCI) is a serious neurological disorder for which there is currently no effective treatment. Telomerase reverse transcriptase (TERT), as the catalytic subunit of telomerase, is closely related to the proliferation and differentiation of astrocytes. This study aims to explore the mechanism of the TERT gene in promoting SCI repair and regeneration by inducing reactive astrocytes (RAs) and its potential application as a therapeutic target. First, the RAs model of TERT gene overexpression was constructed using a lentiviral vector, and its efficiency was verified using qRT-PCR and Western blotting. The effect of TERT expression on the proliferation and apoptosis of RAs was detected using CCK8 and flow cytometry assays. Subsequently, immunofluorescence and Western blotting were used to detect changes in the expression of proteins, such as NFL, Nestin, NSE, and GFAP, as well as their protein interactions with downstream pathways, such as GSK-3β, Klf4, and β-catenin, to further explore the specific mechanism of the TERT gene in SCI regeneration and repair. CCK8 assay showed that the survival rate of RAs increased with the upregulation of TERT expression. Flow cytometry assay showed that TERT expression was negatively correlated with the apoptosis rate of RAs. Immunofluorescence showed that the expression of proteins, such as NFL, GFAP, and Nestin, increased with the upregulation of TERT expression, suggesting that TERT upregulation is involved in the proliferation and neural differentiation of RAs. Furthermore, western blotting showed that after TERT expression was upregulated, GSK-3β expression was significantly downregulated, whereas Klf4, β-catenin, Nestin, and NSE were significantly upregulated compared with the control group. Upregulation of TERT expression enhances the proliferation of RAs and inhibits their apoptosis. The expression level of TERT is positively correlated with the proliferation and neural differentiation of RAs. In addition, these findings suggest that TERT can promote the proliferation and differentiation of RAs by regulating the Wnt/β-catenin pathway, demonstrating the potential of TERT as a therapeutic target for SCI.</p>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"86 3","pages":"e70040"},"PeriodicalIF":2.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147940644","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":"Multifunctional Electrospun Nerve Conduits Enriched With Stem Cells and Bioactive Molecules for Sciatic Nerve Regeneration.","authors":"Tayebeh Sadat Tabatabai, Morteza Alizadeh, Amir Atashi, Arian Ehterami, Mohammad Kamalabadi Farahani, Nariman Rezaei Kolarijani, Majid Salehi","doi":"10.1002/dneu.70022","DOIUrl":"10.1002/dneu.70022","url":null,"abstract":"<p><p>Peripheral nerve injuries are a major clinical challenge, interrupting neural connectivity between the central nervous system (CNS) and peripheral organs. Traumatic events, natural disasters, and accidents often cause these complex injuries. Recent studies highlight the neurogenic potential of dexamethasone, retinoic acid, and umbilical cord blood stem cells in promoting nerve regeneration. Therefore, the aim of this study was to design electrospun conduits based on PLCL, gelatin, and collagen, along with dexamethasone, retinoic acid, carboxymethyl chitosan, and umbilical cord blood cells to repair sciatic nerve injuries. The chemical and physical properties of the conduits, in addition to biocompatibility and cytotoxicity, were evaluated with different experiments. Finally, the conduits were implanted into a 10 mm defect in the mouse sciatic nerve, and tissue regeneration was assessed after 3 months by related tests. The results showed that the presence of dexamethasone in the conduit designed improved biocompatibility, wettability, degradation rate, tensile strength, and increased cell viability. After seeding the umbilical cord blood cells on the conduit, the results showed good efficacy of the conduit, improving sensory and motor function and increasing nerve regeneration. These results indicate the potential of the resulting conduits as a promising tool for repairing nerve injuries and clinical trials.</p>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"86 3","pages":"e70022"},"PeriodicalIF":2.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147765631","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":"Early Isoflurane Exposure Is Associated With Delayed Adolescent Neurobehavioral Deficits, Accompanied by Dysregulation of FOXG1 and EB3.","authors":"Ke Chen, Mengdi Xia, Changhong Li, Zhenhua Ren, Xiaohui Li","doi":"10.1002/dneu.70033","DOIUrl":"10.1002/dneu.70033","url":null,"abstract":"<p><p>Early-life exposure to general anesthetics has been linked to long-term neurodevelopmental risks, yet the underlying mechanisms remain unclear. Using a mouse model, we show that neonatal isoflurane exposure at Postnatal Day 7 leads to age-dependent behavioral alterations, changes in cortical neuronal abundance and layer-specific neuronal density, and dysregulation of cytoskeleton-associated proteins. Isoflurane-exposed mice displayed increased exploratory behavior during early adolescence but developed marked recognition memory deficits by late adolescence. Histological analyses revealed layer-specific disruption of neuronal distribution in the sensory cortex, characterized by reduced neuronal density in layers II-IV and age-dependent changes in inhibitory interneuron composition. Mechanistically, isoflurane reduced the expression of the microtubule plus-end tracking protein EB3 and the transcription factor FOXG1. FOXG1 co-localized with EB3 and β-tubulin in the cytoplasm, supporting a noncanonical, cytoskeleton-associated role. Together, these findings indicated that early isoflurane exposure is associated with altered neuronal density and dysregulation of the cytoskeleton-associated proteins FOXG1 and EB3, suggesting a potential link between anesthesia exposure and long-term neurodevelopmental alterations.</p>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"86 3","pages":"e70033"},"PeriodicalIF":2.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13133545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147812016","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}