Developmental Neurobiology最新文献

{"title":"Neonatal Procedural Pain Disrupts Phosphorylation of KCC2 in the Spinal Cord","authors":"Mathilde Baudat,&nbsp;Elbert A. J Joosten,&nbsp;Sinno H. P. Simons,&nbsp;Daniël L. A. van den Hove,&nbsp;Renzo J. M. Riemens","doi":"10.1002/dneu.22993","DOIUrl":"https://doi.org/10.1002/dneu.22993","url":null,"abstract":"<p>Neonatal procedural pain experienced in the neonatal intensive care unit can lead to long-lasting remodeling of the central nervous system and, in particular, of the spinal nociceptive network. Preclinical studies indicate a disrupted inhibitory versus excitatory balance in the spinal cord due to reduced γ-aminobutyric acid (GABA) ergic neurotransmission. During neonatal development a GABAergic shift occurs, which is regulated by the potassium-chloride co-transporter 2 (KCC2) and its oxytocin receptor (OXTR)-dependent phosphorylation at the serine 940 residue (pKCC2). As DNA methylation of <i>Oxtr</i> is sensitive to early life adversity, such as neonatal procedural pain, we hypothesized that neonatal procedural pain reduces <i>Oxtr</i> methylation in the lumbar spinal cord and subsequently prevents the developmental increase in KCC2 and pKCC2. Using a rat model of repetitive neonatal procedural pain, four needle pricks were applied to the left hind paw every day from postnatal day (P)0 to P7. Spinal cord samples were collected at P0 and P10 to assess the levels of KCC2 and pKCC2 via Western blot analysis. Additionally, spinal <i>Oxtr</i> methylation was quantified using bisulfite pyrosequencing. The results indicated that neonatal procedural pain downregulates spinal pKCC2 levels, while KCC2 levels remain unchanged. These findings suggest a disrupted KCC2-dependent chloride outflow and support the hypothesis that neonatal procedural pain disrupts the GABAergic shift. A developmental decrease in pKCC2/KCC2 levels was also observed in the ipsilateral spinal cord of P10 animals, indicating the involvement of other post-translational mechanisms in the developmental regulation of spinal KCC2. Methylation of the <i>Oxtr</i> does not seem to be related to the disturbed GABAergic shift, given that no significant changes in <i>Oxtr</i> promoter methylation were detected. Overall, this study demonstrates that neonatal procedural pain disrupts spinal KCC2 phosphorylation and supports the hypothesis that neonatal procedural pain alters the GABAergic shift in the spinal cord.</p>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"85 4","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dneu.22993","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144814685","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":"Could the Polymorphisms of DOCK4 (rs147636134), SYNGAP1 (rs199759879), and FOXP1 (rs767001715) be the Primary Risk Factors for Bipolar Disorder and Autism Spectrum Disorder?","authors":"Elvan Çiftçi,&nbsp;Nimet Sağlam,&nbsp;Tayfun Gözler,&nbsp;İpek Yüksel,&nbsp;Neriman Kilit,&nbsp;İlknur Bozkurt,&nbsp;Muhsin Konuk,&nbsp;Korkut Ulucan,&nbsp;Nevzat Tarhan","doi":"10.1002/dneu.22995","DOIUrl":"https://doi.org/10.1002/dneu.22995","url":null,"abstract":"<p>Autism spectrum disorder (ASD) and bipolar disorder (BD) are psychiatric diseases that may overlap in common neurodevelopmental and genetic basis. Forkhead Box P1 (FOXP1), Synaptic Ras GTPase-activating protein 1 (SYNGAP1), and Dedicator of Cytokinesis 4 (DOCK4) genes are critical for synaptic plasticity, neuronal communication, and brain development. This study aims to investigate the association of <i>FOXP1</i> (rs767001715), <i>SYNGAP1</i> (rs199759879), and <i>DOCK4</i> (rs147636134) polymorphisms with ASD and BD and to determine the effects of genetic variations on disease pathogenesis in the Turkish population. This study was conducted with a total of 200 participants, including 50 ASD patients, 50 BD patients, and 100 healthy controls. DNA was isolated from peripheral blood samples, and <i>FOXP1</i>, <i>SYNGAP1</i>, and <i>DOCK4</i> polymorphisms were genotyped using real-time PCR. The distribution of genetic variants was compared between patient groups and healthy controls. The chi-square test was applied for statistical analyses. In terms of <i>FOXP1</i> (rs767001715), <i>SYNGAP1</i> (rs199759879), and <i>DOCK4</i> (rs147636134) polymorphisms examined in the study, no statistically significant difference was found between the ASD and BD patient groups and the healthy control group (<i>p</i> &gt; 0.05) in the Turkish population. In addition, it was determined that these variants had allele frequencies compatible with global population data. However, due to the limited sample size, these results cannot be generalized. Further large-scale population analyses and functional studies are needed to investigate the association of these genes with ASD and BD in more detail.</p>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"85 4","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dneu.22995","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144814683","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":"Efficacy of midazolam in the Treatment of Acute Convulsions in Children and Its Effects on Convulsive Brain Tissue Injury","authors":"Jing Zhang,&nbsp;Jing Dong,&nbsp;Ling Jiang,&nbsp;Lin Ge,&nbsp;Ran Dong","doi":"10.1002/dneu.22992","DOIUrl":"https://doi.org/10.1002/dneu.22992","url":null,"abstract":"<div>\u0000 \u0000 <p>This study focused on addressing the efficacy of midazolam in the treatment of acute convulsions in children and its effects on convulsive brain tissue injury.</p>\u0000 <p>A total of 124 children with acute convulsions were separated into the control group and the observation group according to the random number table method. Children in the control group received intravenous injection therapy with diazepam (0.3–0.5 mg/kg); those in the observation group received midazolam buccal mucosa administration treatment (different doses for different age groups). The total effective rate of treatment and adverse reactions were observed. The number of children whose convulsions were controlled within 1, 3, and 5 minutes after medication, the time to initial convulsion control, the number of children who experienced recurrence within 10 minutes after control, and the time to recurrence control were recorded. Juvenile (21-day-old) Sprague-Dawley rats were separated into blank control, model, low-dose midazolam, medium-dose midazolam, and high-dose midazolam groups. Rats in the midazolam groups were injected intraperitoneally with different doses of midazolam. The convulsive model rats were prepared by intraperitoneal injection of pentylenetetrazol, and the emergence time and duration time of convulsions were recorded. The convulsion grade of rats was evaluated. The rats were euthanized, and their brain tissues were taken. The pathological morphological changes in the brain tissues were observed, and glial fibrillary acidic protein (GFAP) and gamma-aminobutyric acid (GABA) expression levels in the brain tissues were tested.</p>\u0000 <p>The observation group demonstrated a higher total effective treatment rate, a greater number of children whose convulsions were controlled within 3 and 5 minutes of treatment, a shorter average time to convulsion control, a lower recurrence rate within 10 minutes after initial control, a shorter time to control recurrent convulsions, and a lower incidence of adverse reactions compared to the control group. Convulsive model rats that received medium- and high-dose midazolam displayed prolonged emergence time of convulsions, shorter duration, and lower convulsion grade. In convulsive model rats, the nucleus of hippocampal neurons was deeply stained and showed pyknosis; the arrangement of neurons was disordered; the cells were loose and edematous. In the convulsive model, rats received medium- and high-dose midazolam, and the neuron pyknosis and cell oedema were alleviated. In the hippocampus of convulsive model, rats received high-dose midazolam, GFAP expression levels were reduced, and GABA expression levels were raised (<i>p</i> &lt; 0.05).</p>\u0000 <p>For children with acute convulsions, midazolam buccal mucosa administration can rapidly control convulsive seizures and reduce recurrence rates with high safety. High-dose midazolam can ameliorate brain tissue injury in convulsed rats, redu","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"85 4","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144767859","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":"EMC10 Gene Variants May Cause Dual Molecular Effects on the Neuropsychiatric Disease Pattern","authors":"Hilmi Bolat,&nbsp;Dilan Genç Akdağ,&nbsp;Gül Ünsel-Bolat","doi":"10.1002/dneu.22994","DOIUrl":"https://doi.org/10.1002/dneu.22994","url":null,"abstract":"<div>\u0000 \u0000 <p>The <i>EMC10</i> gene on chromosome 19 encodes one of the highly conserved endoplasmic reticulum membrane complexes (EMC). Specific mutations in <i>EMC10</i> cause a disorder known as neurodevelopmental disorder with dysmorphic facies and variable seizures (NEDDFAS) (OMIM #619264), characterized by global developmental delay and dysmorphic facial features, which become apparent in early childhood. This study aims to present the clinical data associated with a novel variant of a patient diagnosed with NEDDFAS (OMIM #619264), a condition rarely reported in the literature. By examining the phenotypic implications and molecular mechanisms of pathogenic variants in the <i>EMC10</i> gene, this study seeks to contribute to a better understanding of the genetic and clinical spectrum of the disease. Our case was followed up in the Child and Adolescent Psychiatry clinic with the diagnosis of intellectual disability. Initial genetic testing included karyotype analysis, <i>FMR1</i> CGG repeat analysis, and chromosomal microarray analysis. Subsequently, whole-exome sequencing (WES) was performed, and Sanger sequencing was used to confirm the identified variant and conduct familial segregation analysis. We identified a novel homozygous frameshift variant in the <i>EMC10</i> gene, NM_206538.4:c.431del, resulting in NP_996261.1:p.Asp144AlafsTer3 using WES. This variant was classified as pathogenic (P) according to ACMG criteria, which was clinically relevant to the patient's condition. Segregation analysis revealed that both the mother and the father were heterozygous carriers of this variant. To date, the phenotype associated with this variant has been reported in 31 individuals from 16 different families. To our knowledge, our case is the first reported patient in the Turkish population carrying an <i>EMC10</i> gene variant. Among reported cases, variations in symptom distribution and severity have been observed. We propose that <i>EMC10</i> gene variants may exhibit dual molecular effects. There are two types of neurodevelopmental clinical presentations: (1) a classic disease pattern with mild-to-moderate intellectual disability (ID) and no neurological findings and (2) a progressive disease pattern with severe ID, hypotonia, and abnormalities in gait.</p>\u0000 </div>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"85 4","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144740520","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":"Prolactin Secretion During Postnatal Development in Artificial Rearing Rats (Rattus norvegicus)","authors":"César G. Toriz,&nbsp;Ángel I. Melo,&nbsp;Brenda B. García-Iglesias,&nbsp;Carmen Solano-Agama,&nbsp;María de los Ángeles Martínez-Muñoz,&nbsp;Elsa Liliana Aguirre-Benítez,&nbsp;Verónica Rodríguez-Mata,&nbsp;Dulce Ávila-Rodríguez,&nbsp;Margarita González-del-Pliego,&nbsp;Armando Pérez-Torres,&nbsp;Ismael Jiménez-Estrada,&nbsp;Benjamín Floran-Garduño,&nbsp;María Eugenia Mendoza-Garrido","doi":"10.1002/dneu.22985","DOIUrl":"https://doi.org/10.1002/dneu.22985","url":null,"abstract":"<p>During the lactation period, rat pups are fed by their mother and are with their siblings. In the pituitary, lactotrope and somatolactotrope cells increase in number during this period and are associated with milk-borne factors. In the artificial rearing (AR) paradigm, pups are deprived of mother– and sibling–pup interactions and are fed artificial milk. AR rats present more hypothalamic neurons associated with less apoptosis during postnatal development. Moreover, AR infantile rats show growth hormone (GH), insulin-like growth factor-1 (IGF-1), and ghrelin alterations resulting from suckling behavior and the absence of meal transition at the second week of life. In the present study, the variation in prolactin (PRL) throughout the lactation period was analyzed in AR pups and compared with that in mother-reared (MR) pups. At postnatal Day 7 (pnd7), AR pups have less serum PRL than MR pups do, and a further decrease was observed at pnd14. However, only at pnd14, AR pituitary cells secrete less PRL, which was correlated with a smaller number of somatolactotrope cells unlike lactotrope cells. Analysis of the hypothalamic dopamine and DOPAC concentrations in both groups revealed no differences at 7, 14, and 21pnd. Nevertheless, the pituitary showed higher concentrations in AR pups than in MR pups at pnd14. However, the number of dopaminergic neurons in the arcuate nucleus was similar in both groups, but they were less spread in the AR pup hypothalamus. Our results revealed the importance of mothers’ and siblings’ interactions and mothers’ milk in the maturation of the PRL hypothalamic‒pituitary axis during the lactating period.</p>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"85 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dneu.22985","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681595","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":"Robust Brain Tumor Detection and Classification From Multichannel MRI Using Deep Learning","authors":"Prasad A. Y.,&nbsp;Kazuaki Tanaka,&nbsp;Krishnamoorthy R.,&nbsp;R. Thiagarajan","doi":"10.1002/dneu.22991","DOIUrl":"https://doi.org/10.1002/dneu.22991","url":null,"abstract":"<div>\u0000 \u0000 <p>Brain tumor detection and classification from multichannel magnetic resonance imaging (MRI) using deep learning techniques for an accurate detection and classification of brain tumors from multichannel MRI are essential for guiding effective treatment strategies and improving patient outcomes. Traditional methods often struggle with handling large volumes of MRI data, leading to limitations in both efficiency and reliability. This study aims to develop a robust approach for brain tumor detection and classification by leveraging computer vision and deep learning techniques, addressing the limitations of conventional methods. The proposed approach utilizes the dual boundary-sensitive transformation (DBST) algorithm for precise tumor edge detection, whereas the scale-invariant feature transform (SIFT) method provides robust and invariant features for classification. Additionally, deep learning models, DarkNet53 and DenseNet201, are employed to enhance classification performance by learning complex patterns from a large dataset of multichannel MRI images. The dataset used in this study is publicly available, ensuring reproducibility and accessibility of the research. The results show a specificity of 98%, indicating the model's strong ability to correctly identify negative cases, and a sensitivity of 99%, demonstrating its effectiveness in identifying positive cases. This performance significantly surpasses traditional methods and is competitive with state-of-the-art (SOTA) techniques in the field. MATLAB is utilized to implement the models, showcasing the potential of deep learning in medical imaging. Future work will explore more advanced deep learning architectures, incorporate additional modalities, and further refine the techniques to improve accuracy and robustness in brain tumor detection and classification.</p>\u0000 </div>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"85 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666518","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 Impact of Vitamin A Deficiency and Supplementation on Behavioral and Oxidative Stress Markers in Male Offspring of a Valproic Acid-Induced Autism Rat Model","authors":"Kacimi Fatima Ezzahra,&nbsp;Ed-Day Soumia,&nbsp;Nechchadi Habiba,&nbsp;Ibouzineddine Laila,&nbsp;Ramchoun Mhamed,&nbsp;Berrougui Hicham,&nbsp;Azzaoui Fatima-Zahra,&nbsp;Boulbaroud Samira","doi":"10.1002/dneu.22990","DOIUrl":"https://doi.org/10.1002/dneu.22990","url":null,"abstract":"<div>\u0000 \u0000 <p>Autism spectrum disorder (ASD) is a neurodevelopmental condition influenced by genetic and environmental factors, including prenatal nutrition. This study investigates the role of Vitamin A deficiency (VAD) in exacerbating ASD-like behaviors in a valproic acid (VPA)-induced rat model and mitigating effects of Vitamin A supplementation (VAS). Twenty-five pregnant rats were divided into five groups, with treatments including VPA exposure and VAD. Neurodevelopmental and behavioral tests, such as the rollover, negative geotaxis, gait, and open field, assessed motor coordination and social interaction in offspring. VPA and VAD groups showed impaired behaviors, motor deficits, and elevated oxidative stress, marked by reduced superoxide dismutase, catalase, and glutathione levels, alongside increased malondialdehyde, nitrite oxide, and altered acetylcholine activity. VAS partially restored antioxidant defenses and alleviated behavioral symptoms. These findings highlight the exacerbating impact of VAD on ASD-like behaviors and the therapeutic potential of VAS in managing neurodevelopmental and biochemical alterations linked to ASD.</p>\u0000 </div>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"85 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574019","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":"An Efficient Deep Learning Framework for Automated Epileptic Seizure Detection: Toward Scalable and Clinically Applicable Solutions","authors":"Dezan Ji,&nbsp;Haozhou Cui,&nbsp;Haotian Li,&nbsp;Guoyang Liu,&nbsp;Zhen Liu,&nbsp;Wei Shang,&nbsp;Yi Li,&nbsp;Weidong Zhou","doi":"10.1002/dneu.22983","DOIUrl":"https://doi.org/10.1002/dneu.22983","url":null,"abstract":"<div>\u0000 \u0000 <p>In this study, we present an efficient epileptic seizure detection framework driven by a graph convolutional neural network (GCNN). Unlike conventional methods that primarily rely on local features or complex feature engineering, our GCNN-based approach explicitly encodes the spatial dependencies among electroencephalogram (EEG) electrodes, thereby capturing more comprehensive spatiotemporal features. A minimal preprocessing pipeline, consisting only of bandpass filtering and segmenting, reduces system complexity and computational overhead. On the CHB-MIT scalp EEG database, our method achieved an average accuracy of 98.64%, sensitivity of 99.49%, and specificity of 98.64% at the segment-based level and sensitivity of 96.81% with FDR of 0.27/h at the event-based level. On the SH-SDU database we collected, the method yielded segment-based accuracy of 95.23%, sensitivity of 92.42%, and specificity of 95.25%, along with event-based sensitivity of 94.11%. The average testing time for 1 h of multi-channel EEG signals is 3.89 s. These excellent results and low-computation design make the framework especially suited for clinical applications, advancing EEG-based epilepsy diagnostics and improving patient outcomes.</p>\u0000 </div>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"85 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574018","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":"Advancements in Nanotechnology for Autism Spectrum Disorder: Innovative Strategies in Pediatric Neurology","authors":"Haozhen Li,&nbsp;Jing Zhang","doi":"10.1002/dneu.22989","DOIUrl":"https://doi.org/10.1002/dneu.22989","url":null,"abstract":"<div>\u0000 \u0000 <p>Autism spectrum disorder (ASD) presents significant challenges in pediatric neurology, necessitating innovative management strategies to improve outcomes for affected children. This review explores the transformative potential of nanotechnology in autism treatment, highlighting specific applications of nanoscale materials and devices. We provide a detailed examination of various nanotechnology-based interventions, including targeted drug delivery systems that boost therapeutic efficacy, nanosensors for the early detection of ASD, and nanocarriers designed for gene therapy, all aimed at minimizing side effects while maximizing treatment benefits. Additionally, we discuss the role of nanotechnology in developing personalized medicine approaches tailored to the unique neurobiological profiles of children with ASD. By bridging the gap between research and clinical practice, this review aims to enhance the quality of care and life for pediatric patients with autism. We underscore the importance of interdisciplinary collaboration in advancing nanotechnology solutions and call for further research to validate these innovative strategies in pediatric neurology.</p>\u0000 </div>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"85 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144573715","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 Roles of the Numb Protein in Synaptic Development and Plasticity","authors":"Tatiana Sukhanova,&nbsp;M. Katie Renkemeyer,&nbsp;Nicholas Pritchett,&nbsp;Brett Berke,&nbsp;Haig Keshishian","doi":"10.1002/dneu.22988","DOIUrl":"https://doi.org/10.1002/dneu.22988","url":null,"abstract":"<div>\u0000 \u0000 <p>Numb is an adaptor protein with functions that include the endocytic processing of activated growth factor receptors. As growth factor signaling contributes to the development and function of the <i>Drosophila</i> neuromuscular junction (NMJ), we examined whether Numb is present at the larval NMJ and whether it is required for the growth, physiology, and/or plasticity of this synapse. Antisera prepared against Numb protein labeled NMJ presynaptic boutons, and RNAi knockdown of Numb, when directed to the presynaptic side, reduced the size of the NMJ. This was accompanied by smaller excitatory junctional potentials with reduced synaptic quantal content. Numb loss of function also suppressed the activity-dependent expansion of the NMJ, suggesting a requirement for Numb in synaptic growth plasticity. Similar phenotypes have been described at the NMJ for mutations of the Type II BMP growth factor receptor gene <i>wishful thinking (wit)</i>. As Numb is known to participate in growth factor receptor signaling in other systems, we tested whether a genetic interaction exists between the <i>numb</i> and <i>wit</i> genes. We observed a reduction of NMJ size in double heterozygotes compared to the single heterozygote control, suggesting that Numb is a candidate for processing growth factor signals during synaptic development and plasticity at the larval NMJ.</p>\u0000 </div>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"85 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574020","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}