Developmental Neuroscience最新文献

{"title":"Late endosome trafficking is slower in regenerated dendrites.","authors":"Yuting Liu, Vinicius N Duarte, Katherine L Thompson-Peer","doi":"10.1159/dne/aclag007","DOIUrl":"https://doi.org/10.1159/dne/aclag007","url":null,"abstract":"<p><p>Organelle trafficking is essential for neuronal function and homeostasis, particularly in dendrites where transport is required to maintain complex arbors. Following dendritic injury, extensive cellular reorganization occurs during regeneration, yet how this remodeling affects organelle transport dynamics remains poorly understood. To assess the consequences of regeneration on dendritic trafficking, we examined Rab7-labeled late endosome (LE) movement in class IV dendritic arborization neurons of Drosophila after dendrite injury. Using quantitative live imaging analysis, we found that retrograde LE trafficking speed is significantly reduced in regenerated dendrites compared to uninjured controls. However, anterograde LE trafficking speed, the directional bias of LE movement, the proportion of motile versus stationary organelles, LE number, and run length were not significantly different between uninjured versus regenerated neurons at either time point examined. These findings demonstrate that dendritic regeneration selectively impairs retrograde transport kinetics while preserving anterograde transport and directional control mechanisms. Regenerated dendrites are thinner than uninjured controls at early stages of regrowth but recover to normal caliber by later stages, yet retrograde transport deficits persist, suggesting caliber-independent regulation of retrograde transport speed. Our results suggest that altered organelle trafficking dynamics may represent a fundamental consequence of neuronal injury responses, with potential implications for understanding transport defects in regeneration after injury or disease involving dendritic damage.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1"},"PeriodicalIF":2.1,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149197488","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":"Combined Prenatal Environmental Stressors Induce Suprachiasmatic Degeneration with Unexpected Behavioural Resilience in Long-Evans Rats.","authors":"Sabiu Soja, Edem Edem, Adejoke Obajuluwa, Mohammed Abba, Ibrahim Ibrahim, Adeshina Adekeye","doi":"10.1159/dne/aclag001","DOIUrl":"https://doi.org/10.1159/dne/aclag001","url":null,"abstract":"<p><strong>Introduction: </strong>Environmental heat stress and displacement adversity during pregnancy pose significant risks to neurodevelopment, particularly in regions with high maternal mortality and population displacement. The suprachiasmatic nucleus (SCN), the brain's master circadian pacemaker, is vulnerable to prenatal environmental insults, yet the combined impact of thermal and psychosocial stressors on SCN development remains unexplored. We examined the effects of prenatal heat stress and displacement-like conditions on SCN morphology and behaviour across two critical developmental stages.</p><p><strong>Methods: </strong>Twenty-five timed-pregnant Long-Evans rats were exposed to heat stress (38-40°C, 2h daily), displacement conditions (overnight food/water restriction plus overcrowding), combined stressors, or control conditions from gestational days 15-20. Male offspring were assessed at postnatal days 10 (neonatal) and 30 (juvenile).</p><p><strong>Results: </strong>Heat exposure induced significant maternal hyperthermia (2.5-2.9°C elevation). Histological analysis revealed marked SCN cellular degeneration across stress groups at both developmental stages, characterised by reduced cell counts, pyknotic nuclei, and disrupted tissue architecture. Despite structural damage, juvenile behavioural testing revealed paradoxical outcomes: combined stress exposure reduced anxiety-like behaviour in the elevated plus maze, enhanced sociability in three-chamber testing, while preserving recognition memory. Growth analysis demonstrated preferential brain sparing despite reduced somatic growth, with significantly elevated brain-to-body weight ratios in stress-exposed animals.</p><p><strong>Conclusion: </strong>These findings demonstrate that prenatal environmental stressors cause lasting SCN damage but trigger adaptive behavioural responses. The dissociation between structural vulnerability and functional adaptation suggests complex neurodevelopmental programming with implications for populations experiencing heat exposure and displacement adversity.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1"},"PeriodicalIF":2.1,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149168691","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":"Peripheral biomarkers of anxiety in autism and attention deficit/hyperactivity disorder.","authors":"Shane Cleary, Craig Matthews, Grace Teskey, Dawn Bowdish, Jennifer Crosbie, Robert Nicolson, Rosanna Weksberg, Elizabeth Kelley, Jessica Jones, Evdokia Anagnostou, Jane A Foster","doi":"10.1159/dne/aclag006","DOIUrl":"https://doi.org/10.1159/dne/aclag006","url":null,"abstract":"<p><p>Neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD), have high rates of comorbid anxiety disorders. Emerging evidence suggests neuroimmune signalling may partially contribute to behavioural symptoms in NDDs. This study examined the association between neuroinflammation and anxiety symptoms in children and adolescents with NDDs. The sample comprised 134 participants (33 typically developing (TD), 31 ADHD, 70 ASD recruited through the Province of Ontario Neurodevelopmental Disorders (POND) Network. Plasma markers of neuroinflammation were quantified using multiplex immunoassays. Anxiety scores, measured using the Child Behavior Checklist, were significantly higher in ASD and ADHD compared to TD participants. Six neuroinflammatory markers differed between diagnoses, with ASD showing elevated plasma levels of brain-derived neurotrophic factor (BDNF), interleukin-18 (IL-18), and vascular endothelial growth factor (VEGF), while ADHD displayed reduced fractalkine (CXCL1), IL-6, and tumor necrosis factor-α (TNF-α) levels compared to TD. Elastic net regression identified five neuroinflammatory markers, IL-18, β-nerve growth factor (β-NGF), BDNF, soluble receptor for advanced glycation end products (sRAGE), and TNF-α, as predictors of anxiety, collectively explaining 15% of the variance in anxiety levels. These findings reveal associations between peripheral neuroinflammation markers and anxiety in NDDs that reflect complex patterns beyond pro and anti-inflammatory classifications, warranting further investigation as potential biomarkers of behavioral symptoms.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1"},"PeriodicalIF":2.1,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149026637","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":"Cerebellar Cortical Neurogenesis following Exposure to Lipopolysaccharide in Ferret Neonates.","authors":"Shiori Kamiya, Kazuhiko Sawada, Jun Udagawa","doi":"10.1159/dne/aclag005","DOIUrl":"10.1159/dne/aclag005","url":null,"abstract":"<p><strong>Introduction: </strong>Granular neurons arise from external granular precursors (EGPs) in the external granule layer and internal granular progenitors (IGPs) in the internal granular layer (IGL) during cerebellar cortical histogenesis in ferrets. Additionally, IGPs have a potency on differentiating into Bergmann glia and astrocytes. This study aimed to clarify the effects of lipopolysaccharide (LPS) on granular neurogenesis in the developing ferret cerebellum and its association with the proliferation, differentiation, and apoptosis of EGPs and IGPs.</p><p><strong>Methods: </strong>LPS (500 μg/g body weight) was administered to ferrets at postnatal days (PDs) 6 and 7. Ferrets also received 5-ethynyl-2'-deoxyuridine (EdU) and 5-bromo-2'-deoxyuridine (BrdU) on PDs 5 and 7, respectively, to label post-proliferative and proliferating cells at the time of LPS exposure.</p><p><strong>Results: </strong>Two h after BrdU injection (PD 7), the densities of proliferating BrdU- and post-proliferative EdU-labeled cells did not differ in the external granular layer, molecular/Purkinje cell layers (ML/PCL), or IGL between LPS-exposed and control ferrets. BrdU-labeled cells contained 55-83% cells immunostained for proliferating cell nuclear antigen, selectively expressed in IGPs. The S100-immunostained ratio among BrdU-labeled cells was significantly higher in the ML/PCL but lower in the IGL of LPS-exposed ferrets compared to controls. On PD 20, NeuN-positive granular neurons generated on PD 7 (BrdU-labeled) were significantly denser in the IGL of LPS-exposed ferrets.</p><p><strong>Conclusion: </strong>These findings suggest that LPS enhances granular neurogenesis in the developing cerebellum of ferret neonates. LPS may have a location-specific effect on the glial differentiation of proliferating IGPs: enhancing and reducing in the ML/PCL and IGL, respectively.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1"},"PeriodicalIF":2.1,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13688527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148907828","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":"Early Developmental Characterization of Gap-Induced Prepulse Inhibition and Habituation of Auditory Startle Response in a Fragile X Syndrome Mouse Model.","authors":"Abdullah Abdullah, Xiuping Liu, Kartikeya Murari, Jun Yan, Ning Cheng","doi":"10.1159/dne/aclag004","DOIUrl":"10.1159/dne/aclag004","url":null,"abstract":"<p><strong>Introduction: </strong>Atypical sensory processing, particularly auditory hypersensitivity, is a common and debilitating phenotype of fragile X syndrome (FXS). Electrophysiology studies in the FMR1-knockout (KO) mice previously observed hyperexcitability at the auditory cortex (AC), with enhanced neuronal firing to auditory stimuli. Prepulse inhibition, a behavioral measure of sensorimotor gating, is robustly impaired in FXS individuals. Interestingly, a related paradigm called gap-induced inhibition of the acoustic startle (GPIAS) is mediated by the AC, and a previous study observed decreased GPIAS in mature FMR1-KO mice. Further, habituation is also an important sensory filtering mechanism, which has been reported to be impaired in mature FMR1-KO mice. However, not much is known about GPIAS and habituation in the FMR1-KO mice during early development.</p><p><strong>Methods: </strong>We evaluated GPIAS in male and female FMR1-KO mice at post-natal days 15 (P15), 20 (P20), and 30 (P30). The paradigm consisted of a prepulse stimulus (gap in continuous background noise) followed by a startle stimulus, at inter-stimulus intervals of 50 and 100 ms. Habituation was assessed prior to the GPIAS trials, with a series of startle only stimulus.</p><p><strong>Results: </strong>We observed a trend for genotype difference in acoustic startle response (ASR) magnitude, particularly in the female mice at P30. No significant genotype differences were noted in GPIAS or latency of ASR. Response duration was significantly increased in the male FMR1-KO mice compared to their WT counterparts during early development. Significant genotype differences were also observed in habituation and sensitization. In terms of development, we observed a significant increase in GPIAS with maturation. Furthermore, we also observed significant changes in the magnitude, response latency, and duration of ASR with maturation. Finally, significant sex differences were observed in ASR magnitude and duration.</p><p><strong>Conclusion: </strong>Our findings suggest that behavioral responses to auditory stimuli are dynamic during development and differ between females and males. This is an important consideration for future study designs and highlights the need for mechanistic studies to further understand the development- and sex-related differences. Additionally, the FMR1-KO mice display habituation deficits during early development, which could be an ideal window for addressing auditory hypersensitivity in FXS.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1"},"PeriodicalIF":2.1,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13688538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148851665","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 Hypoxia Alters Glucocorticoid Regulation in Adult Female Offspring and Their Embryonic Progeny.","authors":"Sofiya Potapova, Ekaterina Tyulkova, Oleg Vetrovoy","doi":"10.1159/dne/aclag003","DOIUrl":"10.1159/dne/aclag003","url":null,"abstract":"<p><strong>Introduction: </strong>Prenatal hypoxia is a clinically relevant adverse factor that may affect fetal development both directly and through activation of maternal glucocorticoid signaling. The placenta plays a central role in this process by regulating fetal exposure to maternal glucocorticoids, yet it remains unclear whether hypoxia-induced endocrine alterations can extend into the next generation and modify placental and fetal brain glucocorticoid regulation during embryogenesis. Here, we investigated whether maternal hypoxia (MH) programs the glucocorticoid phenotype of adult female offspring and whether this phenotype is associated with altered placental glucocorticoid signaling and fetal brain corticosterone (CORT) exposure in their progeny.</p><p><strong>Methods: </strong>Adult female rats prenatally exposed to MH were examined for 24-h plasma CORT rhythms. These females were then mated with control males, and embryonic tissues from their progeny (progeny of maternal hypoxic [PMH] females) were collected at e14, e16, e18, and e20. CORT concentrations were measured in amniotic fluid and fetal brain, whereas placental and fetal brain expression of glucocorticoid receptor (GR)-related genes and 11β-hydroxysteroid dehydrogenases was assessed by quantitative real-time PCR and Western blotting.</p><p><strong>Results: </strong>MH females showed overall elevation of plasma CORT across the circadian cycle, with a higher fitted MESOR (midline estimating statistic of rhythm, i.e., the rhythm-adjusted mean) and reduced rhythmic robustness. In PMH embryos, maternal and fetal placentas (MP and FP) displayed stage- and compartment-specific changes in Nr3c1 and Fkbp5 expression, accompanied by reduced FP Hsd11b2 mRNA at e14, but no change in HSD11B1 and HSD11B2 protein levels in the MP and FP throughout pregnancy. Amniotic fluid CORT was increased at e14, e16, and e20, whereas fetal brain CORT was elevated at e14 and e16. In fetal brain, Fkbp5 expression increased at e16 and e18, Dusp1 decreased at e20, and Hsd11b1 decreased at e16, whereas GR and HSD11B2 protein levels remained unchanged.</p><p><strong>Conclusion: </strong>These findings indicate that MH is associated with persistent alteration of glucocorticoid regulation in adult female offspring and with developmental stage-specific remodeling of placental glucocorticoid handling and fetal brain glucocorticoid signaling in the next generation. Therefore, we conducted this pilot study to map circadian CORT profiles in female rats exposed to MH and to assess glucocorticoid regulation in their placenta and fetal brain during pregnancy. This approach provided a detailed, temporal understanding of intergenerational glucocorticoid programming.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1"},"PeriodicalIF":2.1,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13688523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148815025","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":"On the Same Wavelength: The Relationship between Neural Synchrony and Cognitive Ability during Movie Watching in Late Childhood and Early Adolescence.","authors":"Kathleen M Lyons, Sara Saljoughi, Wilson Ho, Adrian M Owen, Ryan A Stevenson, Bobby Stojanoski","doi":"10.1159/dne/aclag002","DOIUrl":"10.1159/dne/aclag002","url":null,"abstract":"<p><strong>Introduction: </strong>Cognitive development in late childhood and adolescence occurs alongside increasingly complex environments. The current study examined how cognitive abilities relate to neural processing of naturalistic experiences.</p><p><strong>Methods: </strong>We analyzed fMRI data from 309 children and adolescents (ages 7-15; majority White) in the Healthy Brain Biobank. Participants watched a 10-min clip of Despicable Me during scanning and completed the WISC. Intersubject correlation (ISC) was used to measure brain synchrony during viewing.</p><p><strong>Results: </strong>Adolescents [<xref ref-type=\"bibr\" rid=\"B1\">1</xref>-<xref ref-type=\"bibr\" rid=\"B5\">5</xref>] with higher cognitive scores showed greater ISC in default mode and frontoparietal networks. In contrast, younger children [<xref ref-type=\"bibr\" rid=\"B1\">1</xref>, <xref ref-type=\"bibr\" rid=\"B6\">6</xref>-<xref ref-type=\"bibr\" rid=\"B9\">9</xref>] with high scores showed increased between-subject synchrony only in somatosensory regions.</p><p><strong>Conclusions: </strong>These findings suggest age- and cognition-related differences in how children and adolescents process complex, real-world stimuli.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1"},"PeriodicalIF":2.1,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13688553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148765193","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":"Microbiota-Based Interventions Differentially Rescue Gut and Social Behavior Phenotypes in <italic>Drosophila</italic> with Kdm5 Deficiency.","authors":"Natalia A Peta Martinez, Melanie Reinoso Arnaldi, Tasha M Santiago-Rodriguez, Imilce A Rodriguez-Fernandez","doi":"10.1159/000552681","DOIUrl":"10.1159/000552681","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Autism spectrum disorder (ASD) is a lifelong neurological and developmental disorder that is often accompanied by gastrointestinal (GI) issues. The bidirectional communication system known as the gut microbiota-brain axis may help explain how GI dysfunction contributes to neurological symptoms. Loss-of-function mutations in the histone demethylases KDM5A, KDM5B, or KDM5C are found in patients with intellectual disability and ASD. Here, we use a genetically tractable Drosophila model of loss-of-function of the ASD-associated chromatin regulator Kdm5 to investigate how host genetic disruption influences gut microbial composition and social behavior. Previous studies using a Drosophila Kdm5 loss-of-function (Kdm5LOF) revealed gut microbial dysbiosis, reduced abundance of Lactiplantibacillus plantarum, and impaired social behavior. While L. plantarum supplementation rescued intestinal abnormalities, it did not restore social behavior.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We evaluated multiple microbiota-based interventions, including probiotic supplementation with L. plantarum, Lactobacillus helveticus, their combination, and fecal microbiota transplantation (FMT), to determine their capacity to modulate gut microbial composition and behavior in adult Kdm5LOF flies. Gut bacterial abundance was quantified using colony-forming unit assays and full-length 16S rRNA gene sequencing. Social behavior was assessed using the social distance assay, while anxiety-like behavior and locomotion were evaluated using the open field test. Gut-specific Kdm5 knockdown was used to assess tissue-specific contributions to microbiota and behavioral phenotypes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Kdm5 deficiency resulted in reduced abundance of culturable Lactobacillus, Acetobacter, and Enterobacter species, accompanied by impaired social behavior. L. plantarum supplementation restored gut microbial abundance in both whole-body Kdm5LOF and gut-specific Kdm5 knockdown models but did not significantly rescue social behavior. In contrast, L. helveticus significantly improved social interaction in Kdm5LOF flies despite minimal effects on gut bacterial abundance, revealing a dissociation between microbial restoration and behavioral outcomes. Gut-specific Kdm5 knockdown phenocopied both microbial and social defects observed in Kdm5LOF mutants. Notably, FMT from healthy donors partially restored Lactobacillus abundance, reshaped gut microbial community structure, and partially improved social behavior in Kdm5LOF recipient flies.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Together, these findings identify Kdm5 as a key regulator of gut microbial viability and social behavior and demonstrate that microbiota-based interventions exert strain- and phenotype-specific effects. Our results reveal that restoration of microbial abundance alone is insufficient to rescue social behavior and highlight the importance of functional host-microbe interactions in gut-brain communic","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-21"},"PeriodicalIF":2.1,"publicationDate":"2026-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13412211/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147989881","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 Infection Induces Neuronal Structure and Behavioural Alterations in Experimental Meningitis Rat Model.","authors":"Jayakumar Thejaswini, Veerakalyana Kumar Negetha, Koilmani Emmanuvel Rajan","doi":"10.1159/000551210","DOIUrl":"10.1159/000551210","url":null,"abstract":"<p><strong>Introduction: </strong>Maternal infection (MI) can result in significant neurodevelopmental abnormalities and long-term neurological sequelae in offspring. This study was designed to investigate MI-induced alterations in synaptic protein expression, axonal morphology, dendritic, and spine morphology, and behaviour in a neonatal rat model of bacterial meningitis.</p><p><strong>Methods: </strong>On gestational day 10, pregnant rats were randomly assigned to the following groups: (1) control (Ctrl), (2) MI (pregnant rats were infected with Cronobacter sakazakii by rectovaginal colonization), (3) MI +matrix metalloproteinase inhibitor (MI+MMPI) (C. sakazakii infected pregnant rats received a MMP-9 inhibitor). Male offspring from experimental groups were examined in the novel odor recognition (NOR) test on postnatal day (PND) 15 and the tail suspension test (TST) on PND-60.</p><p><strong>Results: </strong>Offspring from the MI group were impaired in NOR and exhibited depressive behaviour during TST, whereas MI+MMPI group responses were comparable to the Ctrl group. In addition, MI upregulated the expression of tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), MMP-9, and nuclear factor erythroid 2-related factor 2 (Nrf2) in their offspring. In turn, MI downregulating Na+/K+-ATPase activity, postsynaptic density protein (PSD)-95, and multiple ankyrin repeat domain protein (SHANK3) altered the conversion of mature brain-derived neurotrophic factor precursor to mature (mBDNF). Further, MI induced bending and shortening of pyramidal neuronal axon length, reduced dendritic branching complexity, and alerted dendritic and spine morphology. Treatment with MMPI minimized these MI-induced effects.</p><p><strong>Conclusion: </strong>MI can cause microstructural rearrangements in the developing brain and behavioural deficits. Our experimental model mimics the neurological sequelae of neonatal meningitis and could be useful for developing therapeutic strategies.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-13"},"PeriodicalIF":2.1,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13160508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147876483","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":"Intranasal Inhibition of Tropomyosin Receptor Kinase B 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":"10.1159/000552025","url":null,"abstract":"<p><strong>Introduction: </strong>Brain-derived neurotrophic factor 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 8-14 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; however, the ratio of phosphorylated to total TrkB was reduced. 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":"1-11"},"PeriodicalIF":2.1,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13309076/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}