Developmental Neuroscience最新文献

{"title":"Expanding Insights into <italic>KCTD7-</italic>Related Drug-Resistant Epilepsy: Three Novel Mutations in a Cohort of Iranian Pediatric Patients.","authors":"Sima Binaafar, Reza Shervin Badv, Ali Rashidi-Nezhad, Mehrdad Behmanesh","doi":"10.1159/000548627","DOIUrl":"10.1159/000548627","url":null,"abstract":"<p><strong>Introduction: </strong>KCTD7-related epilepsy is a rare neurogenetic disorder characterized by marked genetic and phenotypic heterogeneity, typically presenting with early onset and often exhibiting poor response to conventional antiseizure medications.</p><p><strong>Methods: </strong>We performed exome sequencing in 134 Iranian pediatric patients with drug-resistant epilepsy and selected mutations in the KCTD7 gene. The pathogenicity of the identified variants was assessed using multiple in silico prediction tools and classified according to the ACMG guidelines. Additionally, we reviewed the genotype-phenotype correlations and treatment histories of all reported cases with KCTD7 mutations.</p><p><strong>Results: </strong>Three novel homozygous variants - c.14C>T (p.Thr5Met), c.840delC (p.Ile281Serfs*11), and c.746T>G (p.Val249Gly) - were identified in 4 patients. Significant phenotypic heterogeneity was observed among patients, with disease severity ranging from mild to profound. Independent in silico analyses of each variant yielded concordant results, consistently predicting their potential to impact the structure and function of the KCTD7 protein. To date, 72 patients from 55 families have been reported, including 26.66% of homozygous cases born to non-consanguineous parents and 37% of reported variants localized within BTB domain. Although 88.9% of patients experienced seizure onset before age two, clinical trajectories were highly variable. Among 45 patients with treatment data, valproate, levetiracetam, and clonazepam were the most frequently prescribed antiseizure medications; however, seizure control remained inconsistent. Notably, we observed subfertility in two heterozygous fathers, an unexpected finding that may suggest a potential role for KCTD7 beyond the central nervous system.</p><p><strong>Conclusion: </strong>These findings expand the mutational and phenotypic landscape of KCTD7-related epilepsy and underscore its clinical heterogeneity and therapeutic challenges.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-15"},"PeriodicalIF":2.0,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145151643","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":"Beta Spectral Power during Passive Listening in Preschool Children with Specific Language Impairment.","authors":"Saška Fatić, Nina Stanojević, Ljiljana Jeličić, Ružica Bilibajkić, Maša Marisavljević, Slavica Maksimović, Aleksandar Gavrilović, Miško Subotić","doi":"10.1159/000539135","DOIUrl":"10.1159/000539135","url":null,"abstract":"<p><strong>Introduction: </strong>Children with specific language impairment (SLI) have difficulties in different speech and language domains. Electrophysiological studies have documented that auditory processing in children with SLI is atypical and probably caused by delayed and abnormal auditory maturation. During the resting state, or different auditory tasks, children with SLI show low or high beta spectral power, which could be a clinical correlate for investigating brain rhythms.</p><p><strong>Methods: </strong>The aim of this study was to examine the electrophysiological cortical activity of the beta rhythm while listening to words and nonwords in children with SLI in comparison to typical development (TD) children. The participants were 50 children with SLI, aged 4 and 5 years, and 50 age matched TD children. The children were divided into two subgroups according to age: (1) children 4 years of age; (2) children 5 years of age.</p><p><strong>Results: </strong>The older group differed from the younger group in beta auditory processing, with increased values of beta spectral power in the right frontal, temporal, and parietal regions. In addition, children with SLI have higher beta spectral power than TD children in the bilateral temporal regions.</p><p><strong>Conclusion: </strong>Complex beta auditory activation in TD and SLI children indicates the presence of early changes in functional brain connectivity.</p><p><strong>Introduction: </strong>Children with specific language impairment (SLI) have difficulties in different speech and language domains. Electrophysiological studies have documented that auditory processing in children with SLI is atypical and probably caused by delayed and abnormal auditory maturation. During the resting state, or different auditory tasks, children with SLI show low or high beta spectral power, which could be a clinical correlate for investigating brain rhythms.</p><p><strong>Methods: </strong>The aim of this study was to examine the electrophysiological cortical activity of the beta rhythm while listening to words and nonwords in children with SLI in comparison to typical development (TD) children. The participants were 50 children with SLI, aged 4 and 5 years, and 50 age matched TD children. The children were divided into two subgroups according to age: (1) children 4 years of age; (2) children 5 years of age.</p><p><strong>Results: </strong>The older group differed from the younger group in beta auditory processing, with increased values of beta spectral power in the right frontal, temporal, and parietal regions. In addition, children with SLI have higher beta spectral power than TD children in the bilateral temporal regions.</p><p><strong>Conclusion: </strong>Complex beta auditory activation in TD and SLI children indicates the presence of early changes in functional brain connectivity.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"98-111"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965842/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140899631","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":"Structural and Functional Effects of C5aR1 Antagonism in a Rat Model of Neonatal Hypoxic-Ischemic Encephalopathy.","authors":"Angela Saadat, Haree Pallera, Frank Lattanzio, Daley Owens, Amy Gaines, Sai Susmitha Ravi, Tushar Shah","doi":"10.1159/000539506","DOIUrl":"10.1159/000539506","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;The complement response activates upon reperfusion in neonatal hypoxic-ischemic encephalopathy (HIE) and contributes to excessive neuroinflammation and worse outcomes. C5a is a powerful anaphylatoxin central to each of the complement pathways, and its engagement with C5aR1 is directly tied to brain injury and neuronal death. Reasoning C5aR1 antagonism can decrease excessive neuroinflammation and thereby improve neurological and functional outcomes, we tested this hypothesis in a rat model of HIE with PMX205, a small molecule that inhibits C5a-C5aR1 interaction.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Term-equivalent pups (P10-12) were subjected to mild-moderate HIE by Vannucci's method and treated with PMX205. We compared motor and cognitive outcomes with two behavioral tests each (food handling and accelerod; novel object recognition [NOR] and open field) to improve the accuracy of our conclusions.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Improvements were observed in fine motor function, balance, and exploratory behaviors, but little to no improvement in recognition memory and gross motor function. Lesion area and histological assessments showed robust cortical neuroprotection from treatment but persistent injury to the CA1 region of the hippocampus. Better structural and functional outcomes were seen within 1 day of treatment, suggesting C5aR1 antagonism beyond the latent injury phase may impair recovery. In a dose-response experiment, cerebral area loss from injury was improved only in female rats, suggesting underlying sexual dimorphisms in the complement response.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;These results demonstrate proof-of-concept for targeting C5aR1 signaling in neonatal HIE with PMX205 and underscore the role of sex in hypoxic-ischemic injury.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;The complement response activates upon reperfusion in neonatal hypoxic-ischemic encephalopathy (HIE) and contributes to excessive neuroinflammation and worse outcomes. C5a is a powerful anaphylatoxin central to each of the complement pathways, and its engagement with C5aR1 is directly tied to brain injury and neuronal death. Reasoning C5aR1 antagonism can decrease excessive neuroinflammation and thereby improve neurological and functional outcomes, we tested this hypothesis in a rat model of HIE with PMX205, a small molecule that inhibits C5a-C5aR1 interaction.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Term-equivalent pups (P10-12) were subjected to mild-moderate HIE by Vannucci's method and treated with PMX205. We compared motor and cognitive outcomes with two behavioral tests each (food handling and accelerod; novel object recognition [NOR] and open field) to improve the accuracy of our conclusions.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Improvements were observed in fine motor function, balance, and exploratory behaviors, but little to no improvement in recognition memory and gross motor function. Lesion area and histological assessments showed robus","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"112-126"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141154365","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":"Distinguishing Laterality in Brain Injury in Rabbit Fetal Magnetic Resonance Imaging Using Novel Volume Rendering Techniques.","authors":"Gaurav Ambwani, Zhongjie Shi, Kehuan Luo, Jeong-Won Jeong, Sidhartha Tan","doi":"10.1159/000539212","DOIUrl":"10.1159/000539212","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Our laboratory has been exploring the MRI detection of fetal brain injury, which previously provided a prognostic biomarker for newborn hypertonia in an animal model of cerebral palsy (CP). The biomarker relies on distinct patterns of diffusion-weighted imaging-defined apparent diffusion coefficient (ADC) in fetal brains during uterine hypoxia-ischemia (H-I). Despite the challenges posed by small brains and tissue acquisition, our objective was to differentiate between left and right brain ADC changes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A novel aspect involved utilizing three-dimensional rendering techniques to refine ADC measurements within spheroids encompassing fetal brain tissue. 25-day gestation age of rabbit fetuses underwent global hypoxia due to maternal uterine ischemia.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Successful differentiation of left and right brain regions was achieved in 28% of the fetal brains. Ordinal analysis revealed predominantly higher ADC on the left side compared to the right at baseline and across the entire time series. During H-I and reperfusion-reoxygenation, the right side exhibited a favored percentage change. Among these fetal brains, 73% exhibited the ADC pattern predictive of hypertonia. No significant differences between left and right sides were observed in patterns predicting hypertonia, except for one timepoint during H-I. This study also highlights a balance between left-sided and right-sided alterations within the population.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This study emphasizes the importance of investigating laterality and asymmetric hemispheric lesions for early diagnosis of brain injury, leading to CP. The technological limitations in obtaining a clear picture of the entire fetal brain for every fetus mirror the challenges encountered in human studies.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Our laboratory has been exploring the MRI detection of fetal brain injury, which previously provided a prognostic biomarker for newborn hypertonia in an animal model of cerebral palsy (CP). The biomarker relies on distinct patterns of diffusion-weighted imaging-defined apparent diffusion coefficient (ADC) in fetal brains during uterine hypoxia-ischemia (H-I). Despite the challenges posed by small brains and tissue acquisition, our objective was to differentiate between left and right brain ADC changes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A novel aspect involved utilizing three-dimensional rendering techniques to refine ADC measurements within spheroids encompassing fetal brain tissue. 25-day gestation age of rabbit fetuses underwent global hypoxia due to maternal uterine ischemia.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Successful differentiation of left and right brain regions was achieved in 28% of the fetal brains. Ordinal analysis revealed predominantly higher ADC on the left side compared to the right at baseline and across the entire time series. During H-I and reperfusion-reoxygenation, the ri","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"55-67"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11538374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140863995","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":"Upstream Stimulating Factor 2 Aggravates Spinal Nerve Ligation-Induced Neuropathic Pain in Mice via Regulating SNHG5/miR-181b-5p.","authors":"Mi Chen, Yang Yang, Jiatian Cui, Li Qiu, Xiaohua Zou, Xianggang Zeng","doi":"10.1159/000538178","DOIUrl":"10.1159/000538178","url":null,"abstract":"<p><strong>Introduction: </strong>Upstream stimulating factor 2 (USF2) belongs to basic Helix-Loop-Helix-Leucine zipper transcription factor family, regulating expression of genes involved in immune response or energy metabolism network. Role of USF2 in neuropathic pain was evaluated.</p><p><strong>Methods: </strong>Mice were intraspinally injected with adenovirus for knockdown of USF2 (Ad-shUSF2) and then subjected to spinal nerve ligation (SNL) to induce neuropathic pain. Distribution and expression of USF2 were detected by western blot and immunofluorescence. Mechanical and thermal pain sensitivity were examined by paw withdrawal thresholds (PWT) and paw withdrawal latency (PWL). Chromatin immunoprecipitation (ChIP) and luciferase activity assays were performed to detect binding ability between USF2 and SNHG5.</p><p><strong>Results: </strong>The expression of USF2 was elevated and colocalized with astrocytes and microglia in L5 dorsal root ganglion (DRG) of SNL-induced mice. Injection of Ad-shUSF2 attenuated SNL-induced decrease of PWT and PWL in mice. Knockdown of USF2 increased the level of IL-10 but decreased TNF-α, IL-1β, and IL-6 in SNL-induced mice. Silence of USF2 enhanced protein expression of CD206 while reducing expression of CD16 and CD32 in SNL-induced mice. USF2 binds to promoter of SNHG5 and weakens SNL-induced up-regulation of SNHG5. SNHG5 binds to miR-181b-5p, and miR-181b-5p to interact with CXCL5.</p><p><strong>Conclusion: </strong>Silence of USF2 ameliorated neuropathic pain, suppressed activation of M1 microglia, and inhibited inflammation in SNL-induced mice through regulation of SNHG5/miR-181b-5p/CXCL5 axis. Therefore, USF2/SNHG5/miR-181b-5p/CXCL5 might be a promising target for neuropathic pain. However, the effect of USF2/SNHG5/miR-181b-5p/CXCL5 on neuropathic pain should also be investigated in further research.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-11"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140112098","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":"Ex vivo Magnetic Resonance Imaging of the Human Fetal Brain.","authors":"Jing Zhang, Ruike Chen, Chen Tian, Keqing Zhu, Guoliang Ren, Aimin Bao, Yi Shen, Xiao Li, Yaoyao Zhang, Wenying Qiu, Chao Ma, Jing Zhang, Dan Wu","doi":"10.1159/000542276","DOIUrl":"10.1159/000542276","url":null,"abstract":"<p><strong>Background: </strong>The fetal brain undergoes a dynamic process of development during gestation, marked by well-orchestrated events such as neuronal proliferation, migration, axonal outgrowth, and dendritic arborization, mainly elucidated through histological studies. Ex vivo magnetic resonance imaging (MRI) has emerged as a useful tool for 3D visualization of the developing fetal brain, serving as a complementary tool to traditional histology.</p><p><strong>Summary: </strong>In this review, we summarized the commonly employed ex vivo MRI techniques and their advances in fetal brain imaging, and proposed a standard protocol for postmortem fetal brain specimen collection and fixation. We then provided an overview of ex vivo MRI-based studies on the fetal brain.</p><p><strong>Key messages: </strong>According to our review, ex vivo T1- or T2-weighted structural MRI has contributed to the characterization of the anatomy of transient neuronal proliferative zones, the basal ganglia, and the cortex. Diffusion MRI-related techniques, such as diffusion tensor imaging and tractography, have helped investigate the microstructural patterns of fetal brain tissue, as well as the early emergence and development of neuronal migration pathways and white matter bundles. Ex vivo MRI findings have shown strong histological correlations, supporting the potential of MRI in evaluating the developmental events in the fetal brain. Postmortem MRI examinations have also demonstrated comparable, and in certain cases, superior performance to traditional autopsy in revealing fetal brain abnormalities. In conclusion, ex vivo fetal brain MRI is an invaluable tool that provides unique insights into the early stages of brain development.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"400-417"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12500268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142523525","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":"Heterochronic Development of the Perception of Different Types of Visual Illusions.","authors":"Marcos Rosetti, Vania Navarrete, Valeria Montiel, Miriam Alarcon, Rosa E Ulloa, Péter Szenczi, Marcos Rosetti, Oxána Bánszegi","doi":"10.1159/000543308","DOIUrl":"10.1159/000543308","url":null,"abstract":"<p><strong>Introduction: </strong>The underlying neural and/or perceptual mechanisms of different visual illusions are still unknown; thus, they continue to be the focus of many ongoing studies. Inconsistencies persist in the empirical findings for understanding how the perception of these illusions evolves over the course of development.</p><p><strong>Methods: </strong>We assessed 513 participants between 6.5 and 18.9 years of age, with 103 pairs of illusory and control images spanning five illusion types (Ebbinghaus, Müller-Lyer, Contrast, Moving Snake, and Subjective Contour). Misleading and helpful contexts were added when possible.</p><p><strong>Results: </strong>In general, we found that, except for the Ebbinghaus illusion, susceptibility changes with age: while for the Müller-Lyer it decreases, for the Contrast, Moving Snake, and Kanizsa, susceptibility increases. Across all illusory conditions, participants' decision time decreased with age. Context also influenced the performance and choice latency. We also found a gender difference: boys were less susceptible than girls to Contrast and Moving Snake illusions and were faster to answer in Müller-Lyer illusion trials.</p><p><strong>Conclusion: </strong>The current study found that susceptibility to illusions changes in a manner that is age-specific and, in some cases, sex-specific. The different developmental trajectories of the perception of visual illusions support the idea of the lack of a common neural and/or perceptual process behind them. We can suggest that at least some of the cognitive processes and neural pathways involved develop heterochronically.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"350-361"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933486","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":"Timing of Methamphetamine Exposure during Adolescence Differentially Influences Parvalbumin and Perineuronal Net Immunoreactivity in the Medial Prefrontal Cortex of Female, but Not Male, Rats.","authors":"Amara S Brinks, Lauren K Carrica, Dominic J Tagler, Joshua M Gulley, Janice M Juraska","doi":"10.1159/000538608","DOIUrl":"10.1159/000538608","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Adolescence involves significant reorganization within the medial prefrontal cortex (mPFC), including modifications to inhibitory neurotransmission that may be mediated through parvalbumin (PV) interneurons and their surrounding perineuronal nets (PNNs). These developmental changes, which can result in increased PV neuron activity in adulthood, may be disrupted by drug use resulting in lasting changes in mPFC function and behavior. Methamphetamine (METH), which is a readily available drug used by some adolescents, increases PV neuron activity, and could influence the activity-dependent maturational process of these neurons.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In the present study, we used male and female Sprague-Dawley rats to test the hypothesis that METH exposure influences PV and PNN expression in a sex- and age-specific manner. Rats were injected daily with saline or 3.0 mg/kg METH from early adolescence (30-38 days old), late adolescence (40-48 days old), or young adulthood (60-68 days old). One day following exposure, the effects of METH on PV cells and PNN expression were assessed using immunofluorescent labeling within the mPFC.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;METH exposure did not alter male PV neurons or PNNs. Females exposed in early adolescence or adulthood had more PV-expressing neurons while those exposed in later adolescence had fewer, suggesting distinct windows of vulnerability to changes induced by METH exposure. In addition, females exposed to METH had more PNNs and more intense PV neuron staining, further suggesting that METH exposure in adolescence uniquely influences the development of inhibitory circuits in the female mPFC.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;This study indicates that the timing of METH exposure, even within adolescence, influences its neural effects in females.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Adolescence involves significant reorganization within the medial prefrontal cortex (mPFC), including modifications to inhibitory neurotransmission that may be mediated through parvalbumin (PV) interneurons and their surrounding perineuronal nets (PNNs). These developmental changes, which can result in increased PV neuron activity in adulthood, may be disrupted by drug use resulting in lasting changes in mPFC function and behavior. Methamphetamine (METH), which is a readily available drug used by some adolescents, increases PV neuron activity, and could influence the activity-dependent maturational process of these neurons.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In the present study, we used male and female Sprague-Dawley rats to test the hypothesis that METH exposure influences PV and PNN expression in a sex- and age-specific manner. Rats were injected daily with saline or 3.0 mg/kg METH from early adolescence (30-38 days old), late adolescence (40-48 days old), or young adulthood (60-68 days old). One day following exposure, the effects of METH on PV cells and PNN expression were assessed","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"27-39"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11436475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140319851","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":"Dysregulation of Brain Cholesterol Biosynthetic Pathway following Hypoxia Ischemia in Neonatal Mice.","authors":"Fuxin Lu, Celeste Yen, Chase D Corley, Jeffrey G McDonald, Tiina Manninen, Nicholas R Stewart, Christina M Zhu, Donna M Ferriero, Xiangning Jiang","doi":"10.1159/000543254","DOIUrl":"10.1159/000543254","url":null,"abstract":"<p><p><p>Introduction: Brain cholesterol relies on de novo biosynthesis and is crucial for brain development. Cholesterol synthesis is a complex series of reactions that involves more than twenty enzymes to reach the final product and generates a large number of intermediate sterols along two alternate pathways. This is a highly regulated and oxygen-dependent process and thus sensitive to hypoxia.</p><p><strong>Methods: </strong>Using the modified Vannucci procedure, a clinically relevant animal model of neonatal hypoxia ischemia (HI), we characterized the profile of cholesterol and its sterol intermediates, along with the key enzymes on the cholesterol synthetic pathway over a time course of 5 days after HI in the postnatal day 10 mouse brain.</p><p><strong>Results: </strong>Although the total cholesterol levels in the injured cortices appeared to be minimally attenuated at 5 days following HI, there was an overall repression of brain cholesterol biosynthesis. Lanosterol and the downstream sterols in both the Bloch and Kandutsch-Russell (K-R) pathways were consistently reduced for up to 3 days except for desmosterol, which was elevated. Correspondingly, protein expression of the controlling transcription factors sterol regulatory element-binding protein 2 (SREBP-2) and SREBP-1 was decreased at early time points (within 6 h), in parallel with the downregulation of several substrate enzymes for up to 5 days post-HI. HMG-CoA reductase (HMGCR), the first rate-limiting enzyme, was upregulated in the first 24 h after HI. The expression of 24-dehydrocholesterol reductase (DHCR24) that catalyzes the last step to produce cholesterol on the Bloch pathway and bridges the Bloch to K-R pathway was also augmented.</p><p><strong>Conclusions: </strong>Our data suggest perturbed brain cholesterol biosynthesis following neonatal HI. As some sterol intermediates and enzymes have diverse functions in brain development and stress responses other than producing cholesterol, assessment of their dynamic changes after HI is important to understand the lipid responses in rodent HI models and to identify lipid-based targeted therapies in future studies. </p>.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"333-349"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142878360","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":"GAPDH, β-Actin, and β-Tubulin Display Age-Dependent Protein Expression Changes in the Mouse Cortex during Development.","authors":"Daniella Rodriguez, Michelle Nguyen, Tejas Devata, Deval Patel, Diana Tavares-Ferreira, Lena H Nguyen","doi":"10.1159/000544064","DOIUrl":"10.1159/000544064","url":null,"abstract":"<p><strong>Introduction: </strong>GAPDH, β-actin, and β-tubulin are essential housekeeping proteins commonly used as reference controls for protein expression studies. GAPDH is a key glycolytic enzyme that facilitates the production of cellular energy, while β-actin and β-tubulin are major structural components of the cytoskeleton. Besides their well-established housekeeping functions, emerging studies have demonstrated critical roles for these proteins in brain developmental and pathological processes. However, few studies have examined how the expression patterns of these proteins change throughout mammalian brain development to adulthood. Considering the dynamic structural and functional changes that occur during brain development and the roles of GAPDH, β-actin, and β-tubulin in related biological processes, we investigated the developmental expression levels of these proteins in the mouse cortex at various embryonic and postnatal stages.</p><p><strong>Methods: </strong>Cortical tissue was collected from mice at embryonic days 15 and 17, postnatal days 0, 5, 10, 15, 20, and during adulthood. Protein levels were analyzed using western blotting analysis with total protein normalization.</p><p><strong>Results: </strong>We identified a substantial increase in GAPDH protein levels and a decrease in β-actin and β-tubulin protein levels in the mouse cortex between birth and early adulthood, which occurred during the second week of postnatal life. Analysis of RNA-seq data from the ENCODE Consortium revealed correlated changes at the RNA transcript level.</p><p><strong>Conclusion: </strong>Overall, our study reveals robust age-dependent changes in cortical GAPDH, β-actin, and β-tubulin expression levels during mouse postnatal development and suggests precautions when using these proteins as reference controls in cortical development studies.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"498-509"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143392471","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}