Developmental Neurobiology最新文献_第2页

Developmental Trajectory of Auditory Brainstem Deficits in a Mouse Model of Fetal Alcohol Spectrum Disorders 胎儿酒精谱系障碍小鼠模型听觉脑干缺陷的发育轨迹

IF 2 4区医学

Developmental Neurobiology Pub Date : 2026-09-15 DOI: 10.1002/dneu.70059

Michael Douchey, Stephanie Huntwork, Cassidy Sandstedt, Ragunathan Padmashri

{"title":"Developmental Trajectory of Auditory Brainstem Deficits in a Mouse Model of Fetal Alcohol Spectrum Disorders","authors":"Michael Douchey, Stephanie Huntwork, Cassidy Sandstedt, Ragunathan Padmashri","doi":"10.1002/dneu.70059","DOIUrl":"10.1002/dneu.70059","url":null,"abstract":"Individuals with fetal alcohol spectrum disorders exhibit impaired auditory processing and atypical auditory behaviors across the disorder's spectrum. Although low to moderate prenatal alcohol exposure (PAE) is a prevalent type of exposure, the developmental trajectory of auditory processing deficits resulting from this level of exposure remains unknown. To examine the effects of PAE in the auditory system, we utilized the maternal voluntary alcohol consumption paradigm to model chronic low to moderate PAE throughout gestation. We measured auditory brainstem responses (ABRs) in juvenile mice (postnatal day 16–19) and longitudinally across early adolescence (4–5 weeks), late adolescence (7–8 weeks), and young adulthood (12–14 weeks). ABR abnormalities were first observed in juvenile PAE mice. The effects of PAE on brainstem auditory processing were most prominent in early adolescence, largely dissipated in late adolescence, and showed a reemergence in early adulthood. PAE mice showed elevated ABR thresholds, prolonged wave latencies, and reduced wave amplitudes. Ratios of ABR peak 3 relative to the first ABR peak indicated that the auditory brainstem pathways were hyperactive in PAE mice. The amplitude ratio was found to be elevated from early adolescence to early adulthood, suggesting that PAE has a persistent effect on auditory processing. We found a significant correlation between the amplitude ratios in early adolescent PAE mice and dam ethanol consumption, which point toward dose-dependent brainstem gain dysregulation. Our study shows multilevel auditory alterations highlighting the vulnerability of central auditory pathways to PAE and fills an important gap in understanding auditory processing deficits in a clinically relevant exposure model.","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"86 4","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13578856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148976052","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}

引用次数: 0

Oxytocin Affects Barriergenesis in the Blood–Brain Barrier and the Blood–Cerebrospinal Fluid Barrier In Vitro Monoculture Transwell Models 体外单培养Transwell模型中催产素影响血脑屏障和血脑脊液屏障屏障的屏障形成

IF 2 4区医学

Developmental Neurobiology Pub Date : 2026-08-31 DOI: 10.1002/dneu.70058

Anton S. Averchuk, Olga P. Aleksandrova, Victoria I. Zhdankina, Elizaveta S. Perepelitsa, Arseniy K. Berdnikov, Ksenia О. Salina, Stanislav О. Yurchenko, Alla B. Salmina

{"title":"Oxytocin Affects Barriergenesis in the Blood–Brain Barrier and the Blood–Cerebrospinal Fluid Barrier In Vitro Monoculture Transwell Models","authors":"Anton S. Averchuk, Olga P. Aleksandrova, Victoria I. Zhdankina, Elizaveta S. Perepelitsa, Arseniy K. Berdnikov, Ksenia О. Salina, Stanislav О. Yurchenko, Alla B. Salmina","doi":"10.1002/dneu.70058","DOIUrl":"10.1002/dneu.70058","url":null,"abstract":"<div>\u0000 \u0000 The integrity of the brain's barrier systems—the blood–brain barrier (BBB) and blood–cerebrospinal fluid barrier (BCSFB)—is crucial for central nervous system homeostasis. Oxytocin (OXT), a neuropeptide with emerging peripheral roles, has been implicated in vascular function. This study investigates the hypothesis that OXT directly modulates the functional properties of the BBB and BCSFB via receptor-mediated mechanisms. Using Transwell monoculture in vitro models employing primary rat brain microvascular endothelial cells (BMECs) and choroid plexus epithelial cells (ChPlECs), we first confirmed biological purity and demonstrated constitutive expression of both OXT receptor (OXTR) and the receptor for advanced glycation end products (RAGE) in both cell types. Notably, OXTR and RAGE expression were significantly higher in choroid plexus cells compared to BMECs. Treatment with 800 nM OXT significantly increased transendothelial/epithelial electrical resistance (TEER) in both models, indicating enhanced barrier tightness, with a more rapid effect observed in the BCSFB model. However, paracellular permeability to Lucifer yellow remained unchanged. OXT treatment induced a transient increase in lactoperoxidase (LPO) levels in the conditioned medium at 24 h, followed by a decline at 48–72 h, coinciding with peak TEER values. These findings establish OXT as a potent modulator of cerebral barrier function, with the BCSFB exhibiting higher sensitivity. This novel role of OXT in barrier regulation extends its physiological repertoire and presents a potential therapeutic avenue for neurodevelopmental and neurodegenerative disorders associated with barrier dysfunction.\u0000 </div>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"86 4","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148864043","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}

引用次数: 0

Does the Gut Microbiota Play a Role in Attention-Deficit/Hyperactivity Disorder in Childhood? A Pilot Study From Turkey 肠道微生物群在儿童注意力缺陷/多动障碍中起作用吗？一项来自土耳其的试点研究。

IF 2 4区医学

Developmental Neurobiology Pub Date : 2026-08-31 DOI: 10.1002/dneu.70057

Cansın Kardelen Akyol, Öznur Bilaç, Fethi Sırrı Çam

{"title":"Does the Gut Microbiota Play a Role in Attention-Deficit/Hyperactivity Disorder in Childhood? A Pilot Study From Turkey","authors":"Cansın Kardelen Akyol, Öznur Bilaç, Fethi Sırrı Çam","doi":"10.1002/dneu.70057","DOIUrl":"10.1002/dneu.70057","url":null,"abstract":"<div>\u0000 \u0000 The pathophysiology of attention-deficit/hyperactivity disorder (ADHD) is not fully understood, but increasing evidence suggests that gut microbiota may play a role. This study compared the gut microbiota of children with ADHD with that of a control group of healthy children, and examined their dietary and sleep habits. Ten medication-naïve children aged 612 years who had recently been diagnosed with ADHD and ten healthy controls were included. ADHD diagnoses were confirmed using the Schedule for Affective Disorders and Schizophrenia for School-Age ChildrenPresent and Lifetime Version (K-SADS-PL). Sleep and eating habits were assessed using the 2nd Level Sleep Disorder Short Form, the Children's Eating Behaviour Inventory, and a form to collect sociodemographic and clinical information. The gut microbiota were analysed using 16S NGS metagenome analysis. A significant decrease in the Shannon and Simpson diversity index values was observed in the ADHD group compared to the control group. Despite the presence of a percentage difference, no statistically significant differences were observed between the groups with respect to species, genus, family, order, class or phylum. Following evaluation of the sleep and eating habit scale scores, no statistically significant difference between the groups was determined.These findings suggests that children with ADHD may alter gut microbiota diversity.However, the absence of significant taxonomic differences and the small sample size mean that these results should be interpreted with caution. Further, larger, adequately powered studies are needed to validate these findings and clarify the potential role of gut microbiota in the pathophysiology of ADHD.\u0000 </div>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"86 4","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148864014","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}

引用次数: 0

Cognitive and Pyroptotic Outcomes of Neonatal Ketamine and Dexmedetomidine: Potential Neuroprotection via Caspase-1 Modulation 新生儿氯胺酮和右美托咪定的认知和焦亡结局：通过Caspase-1调节的潜在神经保护作用。

IF 2 4区医学

Developmental Neurobiology Pub Date : 2026-08-16 DOI: 10.1002/dneu.70056

Simay Alcan-Kirtas, Ozbeyen Atalay, Gokhan Burcin Kubat, Meltem Tuncer

{"title":"Cognitive and Pyroptotic Outcomes of Neonatal Ketamine and Dexmedetomidine: Potential Neuroprotection via Caspase-1 Modulation","authors":"Simay Alcan-Kirtas, Ozbeyen Atalay, Gokhan Burcin Kubat, Meltem Tuncer","doi":"10.1002/dneu.70056","DOIUrl":"10.1002/dneu.70056","url":null,"abstract":"<div>\u0000 \u0000 Neurotoxicity induced by the repeated anesthetic exposure during the neurodevelopmental period and its potential long-term cognitive consequences remain a matter of concern. This study investigated the neurobiological and histological changes in the hippocampus as well as potential long-term neurobehavioral alterations, following repeated administration of ketamine (KET) and dexmedetomidine (DEX) in neonatal rats. Postnatal Day 7 (PND7) rat pups were randomly assigned to four groups: Control (0.9% NaCl), KET (50 mg/kg), DEX (25 µg/kg), and DEXKET (DEX (25 µg/kg) + KET (50 mg/kg)). Intraperitoneal (i.p.) injections were performed for three consecutive days (PND8-10). Developmental neurotoxicity was assessed by measuring apoptotic markers (caspase-3, Bax, and Bcl-2) and pyroptosis-related proteins (caspase-1, gasdermin D, IL-1β, and IL-18) in hippocampus via ELISA. Western blotting was used to analyze long-term hippocampal caspase-1, brain-derived neurotrophic factor (BDNF), and growth associated protein 43 (GAP43) levels. Long-term cognitive effects, including learning, memory, and attention, were evaluated on PND40 using the Barnes maze and the novel object recognition (NOR) tests. Hippocampal morphology was examined by Nissl staining. Although KET or DEX alone did not alter classical apoptotic pathways, they significantly reduced caspase-1. However, both KET and DEX alone impaired recognition memory and attention in the long term, without altering spatial learning. Notably, the combined administration of KET and DEX enhanced sedation while maintaining caspase-1, BDNF, and GAP43 levels close to control values, preserving recognition memory and spatial learning. These findings indicate that co-administration of KET and DEX during the neonatal period may provide a safer anesthetic strategy by reducing cognitive side effects and modulating neuroinflammatory pathways.\u0000 </div>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"86 4","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148764508","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}

引用次数: 0

Impaired Motor Function in a Zebrafish Stathmin-2 Knockout Model 斑马鱼Stathmin-2敲除模型的运动功能受损。

IF 2 4区医学

Developmental Neurobiology Pub Date : 2026-07-28 DOI: 10.1002/dneu.70054

Tyler J. N. Gurberg, Ziyaan A. Harji, Christian J. Rampal, Joséphine Sacy-Richer, Amy Wang, Esteban C. Rodríguez, Gary A. B. Armstrong

{"title":"Impaired Motor Function in a Zebrafish Stathmin-2 Knockout Model","authors":"Tyler J. N. Gurberg, Ziyaan A. Harji, Christian J. Rampal, Joséphine Sacy-Richer, Amy Wang, Esteban C. Rodríguez, Gary A. B. Armstrong","doi":"10.1002/dneu.70054","DOIUrl":"10.1002/dneu.70054","url":null,"abstract":"Stathmin-2 (STMN2) is a microtubule-associated protein that plays a role in the stability of microtubules in axons of the nervous system of animals. In this study, we generated a novel zebrafish STMN2 knockout (KO) model. STMN2 is represented by two genes in the zebrafish genome: stmn2a and stmn2b. Using the CRISPR/Cas9 mutagenic system, we selected founder fish lines harboring frameshift mutations in both genes and bred these together to generate a double stmn2a and stmn2b KO model. Using these models, we observed increased developmental lethality in our double stmn2a and stmn2b KO model and impaired motor function at embryonic stages of development. Examination of the neuromuscular junction (NMJ) revealed a slight increase in the number of orphaned NMJs in trunk musculature as well as a reduction in the amplitude of miniature endplate currents in our double stmn2a and stmn2b KO model. In a final series of experiments, we show impaired ventral root axon regrowth following transection in double stmn2a and stmn2b KO zebrafish. Our findings suggest that while not essential for motor function development, loss of stmn2a and stmn2b expression results in a minor motor phenotype and impairs the ability to regenerate motor axons following injury.","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"86 4","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dneu.70054","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148600380","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}

引用次数: 0

Is There Any Difference in the Novel Serum Inflammatory Biomarkers of Adolescents With DMDD and Bipolar Disorder? 青少年DMDD和双相情感障碍的新型血清炎症生物标志物有区别吗？

IF 2 4区医学

Developmental Neurobiology Pub Date : 2026-07-03 DOI: 10.1002/dneu.70050

Gonca Özyurt, Ezgi Karagöz Tanıgör, Süleyman Emre Özyürek, Kürşat Alperen Korkut, Yusuf Öztürk, Ali Evren Tufan, Hüseyin Burak Baykara, Neslihan İnal

{"title":"Is There Any Difference in the Novel Serum Inflammatory Biomarkers of Adolescents With DMDD and Bipolar Disorder?","authors":"Gonca Özyurt, Ezgi Karagöz Tanıgör, Süleyman Emre Özyürek, Kürşat Alperen Korkut, Yusuf Öztürk, Ali Evren Tufan, Hüseyin Burak Baykara, Neslihan İnal","doi":"10.1002/dneu.70050","DOIUrl":"10.1002/dneu.70050","url":null,"abstract":"<div>\u0000 \u0000 The current study compares the novel serum inflammatory biomarkers of adolescents with disruptive mood dysregulation disorder (DMDD) and bipolar spectrum disorder (BPSD) between the ages of 12 and 18. This study included 24 adolescents with DMDD, 24 adolescents with BPSD, and 24 healthy controls. All adolescents in the study were assessed for novel serum inflammatory biomarkers, including neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), aggregate index of systemic inflammation (AISI), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI). The Affective Reactivity Index was used to assess the degree of irritability. All novel serum inflammatory biomarkers showed significant differences between the groups, with healthy adolescents scoring statistically significantly lower. NLR and PLR were positively correlated with the degree of irritability in all groups. The findings of this study may support that inflammation may play a role in mood disorders.\u0000 </div>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"86 3","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148374781","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}

引用次数: 0

Epigenetic-Based Evidence for Distinct Effects of Age, Sex, and Experience in Developmental Critical Period Learning. 年龄、性别和经验对发育关键期学习的显著影响的表观遗传学证据。

IF 2 4区医学

Developmental Neurobiology Pub Date : 2026-07-01 DOI: 10.1002/dneu.70039

Grant W Kunzelman, Alice Batistuzzo, Sarah E London

{"title":"Epigenetic-Based Evidence for Distinct Effects of Age, Sex, and Experience in Developmental Critical Period Learning.","authors":"Grant W Kunzelman, Alice Batistuzzo, Sarah E London","doi":"10.1002/dneu.70039","DOIUrl":"10.1002/dneu.70039","url":null,"abstract":"Although much is known about the encoding of experience, how the brain organizes neural circuits capable of learning and memory formation is largely unstudied. Canonical critical periods emerge from a convergence of maturation- and experience-dependent processes. Notably, they rely on experience itself to close, resulting in permanent traces of early life. Mechanisms of perceptual critical periods have been well studied, but cognitive critical periods are rare and poorly understood. One well-established critical period for learning is in the juvenile male zebra finch songbird. Juvenile females also perform sensory song learning at ages that overlap with those of the male critical period, though females may learn outside of its age boundaries. The examination of critical period closure thus allows for mechanistic evaluation of the convergence of maturation and experience, plus it provides a unique opportunity to identify neural factors that promote or limit the ability to learn. Because regulated transcription is necessary for the organization and function of cells and circuits, we used a discovery tool (ChIP-seq) for H3K27ac, a strong epigenetic marker of active promoters and enhancers. We examined male and female auditory forebrain, a region necessary for sensory song learning, at two ages and under rearing conditions that affect male critical period closing. We report specific transcription factors, genes, and biological processes that may promote and limit the ability to learn in males, evidence for fluctuations in female developmental plasticity, and evidence that males and females successfully perform sensory song learning using distinct mechanisms.","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"86 3","pages":"e70039"},"PeriodicalIF":2.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148013760","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}

引用次数: 0

From Behavioral and Sleep Disturbances to Genetic Diagnosis: Smith-Magenis Syndrome and the Importance of the Diagnostic Pathway. 从行为和睡眠障碍到基因诊断：史密斯-马格尼斯综合征和诊断途径的重要性。

IF 2 4区医学

Developmental Neurobiology Pub Date : 2026-07-01 DOI: 10.1002/dneu.70051

Fethiye Kılıçaslan, Ayşe Rümeysa Olgar Çetin, Özlem Öz, Mert Coşkun, Mehmet Burak Mutlu, Berna Polat Tüysüz

{"title":"From Behavioral and Sleep Disturbances to Genetic Diagnosis: Smith-Magenis Syndrome and the Importance of the Diagnostic Pathway.","authors":"Fethiye Kılıçaslan, Ayşe Rümeysa Olgar Çetin, Özlem Öz, Mert Coşkun, Mehmet Burak Mutlu, Berna Polat Tüysüz","doi":"10.1002/dneu.70051","DOIUrl":"10.1002/dneu.70051","url":null,"abstract":"Smith-Magenis syndrome (SMS) is a rare multisystem genetic disorder caused by a 17p11.2 microdeletion or pathogenic variants in the retinoic acid-induced 1 (RAI1) gene. It is characterized by developmental delay, distinctive craniofacial features, behavioral dysregulation, and inverted sleep-wake rhythm. Because early clinical findings are often nonspecific, diagnosis is frequently delayed, and patients may initially present to child psychiatry services with behavioral complaints. We report a 5-year-old girl referred for hyperactivity, severe circadian sleep disturbance with recurrent nocturnal awakenings, self-injurious behaviors, sensory-seeking behaviors, and developmental delay. Comprehensive psychiatric, developmental, neurological, physical, and genetic evaluations revealed a 17p11.2 microdeletion involving both RAI1 and folliculin (FLCN). The diagnosis of SMS was confirmed, and the involvement of FLCN indicated additional potential long-term medical risks. This case underscores the importance of considering genetic etiologies in children presenting with severe behavioral dysregulation and sleep problems and highlights the critical role of comprehensive genetic assessment in guiding diagnosis, management, and long-term follow-up.","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"86 3","pages":"e70051"},"PeriodicalIF":2.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13329744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148374762","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}

引用次数: 0

The Ameliorative Effect of Spirulina platensis as Add-On Therapy to Risperidone on Valproic Acid-Induced Autism in Rat Pups: Implication of Oxidative Stress, Inflammatory, and ERK-1/2 Signaling Pathway. 利培酮加用螺旋藻对丙戊酸诱导的自闭症大鼠幼鼠的改善作用：氧化应激、炎症和ERK-1/2信号通路的影响

IF 2 4区医学

Developmental Neurobiology Pub Date : 2026-07-01 DOI: 10.1002/dneu.70052

Setareh Dehkhodaei, Abdolhamid Angaji, Negin Khosravipour, Fatemeh Karamali, Mosayeb Pashaee, Soroush Taherkhani, Razieh Hajisoltani

{"title":"The Ameliorative Effect of Spirulina platensis as Add-On Therapy to Risperidone on Valproic Acid-Induced Autism in Rat Pups: Implication of Oxidative Stress, Inflammatory, and ERK-1/2 Signaling Pathway.","authors":"Setareh Dehkhodaei, Abdolhamid Angaji, Negin Khosravipour, Fatemeh Karamali, Mosayeb Pashaee, Soroush Taherkhani, Razieh Hajisoltani","doi":"10.1002/dneu.70052","DOIUrl":"10.1002/dneu.70052","url":null,"abstract":"Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by social communication deficits and repetitive behaviors. Prenatal exposure to valproic acid (VPA), a teratogenic antiepileptic agent, is known to induce ASD-like symptoms in animal models. This study aimed to assess the therapeutic effects of Spirulina platensis (SP) and Risperidone (Ris) in a VPA-induced autism rat model. Pregnant Wistar rats received a single intraperitoneal dose of VPA (600 mg/kg) on gestational day 12.5. Male offspring received SP (200 mg/kg, p.o.), and/or Ris (1 mg/kg, p.o.), and combination group(Ris+SP) via oral gavage from postnatal day (PND) 23 to PND 52. Behavioral evaluations were performed on PND 52, and biochemical, molecular, and histological analyses were conducted on PND 61, following decapitation. Oxidative stress markers (malondialdehyde [MDA], superoxide dismutase [SOD]), inflammatory cytokines (IL-1β, tumor necrosis factor-alpha [TNF-α]), and extracellular signal-regulated kinase (ERK) protein expression were measured. Nissl staining was used to assess neuronal loss in the prefrontal cortex (PFC). VPA exposure induced anxiety-like behaviors, repetitive actions, impaired social interactions, increased MDA levels, decreased SOD activity, upregulated ERK signaling, elevated IL-1β and TNF-α levels, and neuronal loss in the PFC. Treatment with SP and/or Ris alleviated these deficits, improving behavioral abnormalities, oxidative stress, inflammatory markers, and histological alterations. Combined SP and Ris treatment provided neuroprotective and behavioral improvements in the VPA-induced ASD model, suggesting potential therapeutic roles for ASD interventions.","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"86 3","pages":"e70052"},"PeriodicalIF":2.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148374757","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}

引用次数: 0

Clinical and Molecular Spectrum of Proximal 16p11.2 BP4-5 Copy Number Variations: Insights From a Pediatric Cohort. 近端16p11.2 BP4-5拷贝数变异的临床和分子谱：来自儿科队列的见解

IF 2 4区医学

Developmental Neurobiology Pub Date : 2026-07-01 DOI: 10.1002/dneu.70038

Esra Usluer, Aylin Yüksel Ülker, İbrahim Kaplan

{"title":"Clinical and Molecular Spectrum of Proximal 16p11.2 BP4-5 Copy Number Variations: Insights From a Pediatric Cohort.","authors":"Esra Usluer, Aylin Yüksel Ülker, İbrahim Kaplan","doi":"10.1002/dneu.70038","DOIUrl":"10.1002/dneu.70038","url":null,"abstract":"Copy number variations (CNVs) at the proximal 16p11.2 BP4-BP5 locus are among the most well-characterized genomic regions associated with neurodevelopmental disorders. We aimed to define the clinical and molecular spectrum of these CNVs in a pediatric cohort. A total of 19 patients with pathogenic or likely pathogenic 16p11.2 BP4-BP5 CNVs were identified among 2200 individuals referred for chromosomal microarray analysis (prevalence: 1/116, 0.86%). Deletions were detected in 16/19 (84.2%) patients and duplications in 3/19 (15.8%). Developmental delay/intellectual disability was observed in 12/16 (75%) deletion carriers and 3/3 (100%) duplication carriers. Speech delay was present in 12/16 (75%) and 3/3 (100%), and motor delay in 6/16 (37.5%) and 2/3 (66.6%), respectively. Seizures were identified in 11/16 (68.7%) deletion carriers and 1/3 (33.3%) duplication carriers. Behavioral abnormalities were observed in 6/16 (37.5%) and 2/3 (66.6%), respectively. Neuroimaging data were available in 7/19 patients, with abnormalities detected in 5/7 (71.4%), all of whom had a history of seizures. Structural findings were heterogeneous and included ventricular asymmetry, corpus callosum thinning, and prominence of cerebrospinal fluid spaces. Additional systemic findings included endocrine abnormalities (6/19, 31.6%), skeletal anomalies (4/19, 21.1%), and ophthalmologic findings (3/19, 15.8%). These findings expand the phenotypic spectrum of proximal 16p11.2 BP4-BP5 CNVs and support their early consideration in patients with neurodevelopmental and neurological features, highlighting the need for multidisciplinary evaluation.","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"86 3","pages":"e70038"},"PeriodicalIF":2.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147940675","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}

引用次数: 0