Developmental Neuroscience最新文献

{"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":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>This study indicates that the timing of METH exposure, even within adolescence, influences its neural effects in females.</p><p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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":2.3,"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":"Development of a New Scoring System in Higher Animals for Testing Cognitive Function in the Newborn Period: Effect of Prenatal Hypoxia-Ischemia.","authors":"Zhongjie Shi, Nadiya Sharif, Kehuan Luo, Sidhartha Tan","doi":"10.1159/000538607","DOIUrl":"10.1159/000538607","url":null,"abstract":"<p><strong>Introduction: </strong>Enhanced models for assessing cognitive function in the neonatal period are imperative in higher animals. Postnatal motor deficits, characteristic of cerebral palsy, emerge in newborn kits within our prenatal rabbit model of hypoxia-ischemia (HI). In humans, prenatal HI leads to intellectual disability and cerebral palsy. In a study examining cognitive function in newborn rabbits, we explored several questions. Is there a distinction between conditioned and unconditioned kits? Can the kits discern the human face or the laboratory coat? Do motorically normal kits, born after prenatal HI, exhibit cognitive deficits?</p><p><strong>Methods: </strong>The conditioning protocol was randomly assigned to kits from each litter. For conditioning, the same human, wearing a laboratory coat, fed the rabbit kits for 9 days before the cognitive test. The 6-arm radial maze was chosen for its simplicity and ease of use. Normally appearing kits, born after uterine ischemia at 79% or 92% term in New Zealand White rabbits, were compared to naïve kits. On postpartum day 22/23 or 29/30, the 6-arm maze helped determine if the kits recognized the original feeder from bystander (test 1) or the laboratory coat on bystander (test 2). The use of masks of feeder/bystander (test 3) assessed confounding cues. A weighted score was devised to address variability in entry to maze arms, time, and repeated-trial learning.</p><p><strong>Results: </strong>In conditioned kits, both naïve and HI kits exhibited a significant preference for the face of the feeder but not the laboratory coat. Cognitive deficits were minimal in normal-appearing HI kits.</p><p><strong>Conclusion: </strong>The weighted score was amenable to statistical manipulation.</p><p><strong>Introduction: </strong>Enhanced models for assessing cognitive function in the neonatal period are imperative in higher animals. Postnatal motor deficits, characteristic of cerebral palsy, emerge in newborn kits within our prenatal rabbit model of hypoxia-ischemia (HI). In humans, prenatal HI leads to intellectual disability and cerebral palsy. In a study examining cognitive function in newborn rabbits, we explored several questions. Is there a distinction between conditioned and unconditioned kits? Can the kits discern the human face or the laboratory coat? Do motorically normal kits, born after prenatal HI, exhibit cognitive deficits?</p><p><strong>Methods: </strong>The conditioning protocol was randomly assigned to kits from each litter. For conditioning, the same human, wearing a laboratory coat, fed the rabbit kits for 9 days before the cognitive test. The 6-arm radial maze was chosen for its simplicity and ease of use. Normally appearing kits, born after uterine ischemia at 79% or 92% term in New Zealand White rabbits, were compared to naïve kits. On postpartum day 22/23 or 29/30, the 6-arm maze helped determine if the kits recognized the original feeder from bystander (test 1) or the laborator","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"12-26"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11436483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140319850","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":"Region-Specific Brain Volume Changes Emerge in Adolescence in the Valproic Acid Model of Autism and Parallel Human Findings.","authors":"Cole King, Ivina Mali, Hunter Strating, Elizabeth Fangman, Jenna Neyhard, Macy Payne, Stefan H Bossmann, Bethany Plakke","doi":"10.1159/000538932","DOIUrl":"10.1159/000538932","url":null,"abstract":"<p><strong>Introduction: </strong>Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social and communication deficits, cognitive dysfunction, and stereotyped repetitive behaviors. Regional volume changes are commonly observed in individuals with ASD. To examine volumetric dysregulation across adolescence, the valproic acid (VPA) model was used to induce ASD-like phenotypes in rats.</p><p><strong>Method: </strong>Regional volumes were obtained via magnetic resonance imaging at either postnatal day 28 or postnatal day 40 (P40), which correspond to early and late adolescence, respectively.</p><p><strong>Results: </strong>Consistent with prior research, VPA animals had reduced total brain volume compared to control animals. A novel outcome was that VPA animals had overgrown right hippocampi at P40. Differences in the pattern of development of the anterior cingulate cortex were also observed in VPA animals. Differences for the posterior cingulate were only observed in males, but not females.</p><p><strong>Conclusion: </strong>These results demonstrate differences in region-specific developmental trajectories between control and VPA animals and suggest that the VPA model may capture regional volume changes consistent with human ASD.</p><p><strong>Introduction: </strong>Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social and communication deficits, cognitive dysfunction, and stereotyped repetitive behaviors. Regional volume changes are commonly observed in individuals with ASD. To examine volumetric dysregulation across adolescence, the valproic acid (VPA) model was used to induce ASD-like phenotypes in rats.</p><p><strong>Method: </strong>Regional volumes were obtained via magnetic resonance imaging at either postnatal day 28 or postnatal day 40 (P40), which correspond to early and late adolescence, respectively.</p><p><strong>Results: </strong>Consistent with prior research, VPA animals had reduced total brain volume compared to control animals. A novel outcome was that VPA animals had overgrown right hippocampi at P40. Differences in the pattern of development of the anterior cingulate cortex were also observed in VPA animals. Differences for the posterior cingulate were only observed in males, but not females.</p><p><strong>Conclusion: </strong>These results demonstrate differences in region-specific developmental trajectories between control and VPA animals and suggest that the VPA model may capture regional volume changes consistent with human ASD.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"68-80"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11511791/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140858865","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><strong>Introduction: </strong>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>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-17"},"PeriodicalIF":2.3,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Scutellariae radix Ameliorates Prenatal Stress-Induced Anxiety-Like and Depression-Like Behavior in the Offspring via Reversing HPA Axis Hyperfunction and Ameliorating Neurodevelopmental Dysfunction.","authors":"Lixia Li, Wenying Zhang, Congying Sun, Zhiqiang Chai, Kaiyue Wang, Qian Zhou, Xiaoying Wang","doi":"10.1159/000543152","DOIUrl":"10.1159/000543152","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to explore the impact and mechanism of Scutellariae radix (SR), dried root of Scutellaria baicalensis Georgi of Labiatae, on prenatal stress (PS)-induced anxiety-like and depression-like behavior in the offspring in a mouse prenatal stress model.</p><p><strong>Methods: </strong>The open field test (OFT), tail suspension test (TST), and forced swimming test (FST) were utilized to assess the behavior of the offspring. Histological changes were evaluated using HE staining and Nissl staining. ELISA was employed to detect the levels of related factors in the serum and fetal brains of offspring mice. Immunohistochemistry was used to determine the expressions of doublecortin and neurotrophic factors in the hippocampus, and RT-PCR reflected the expression of factors in the hippocampus and placenta of offspring mice. These various techniques collectively provided insight into the neurodevelopmental status by detecting indicators related to neurodevelopmental status. LC-MS/MS and molecular docking were used to clarify the chemical constituents and the pharmacodynamic components in S. radix.</p><p><strong>Results: </strong>S. radix ameliorated prenatal stress-induced anxiety-like and depression-like behavior in the offspring. It also alleviated hippocampal neurogenesis impairment caused by prenatal stress and restored abnormal expression of hippocampal glutamate (Glu) and brain-derived neurotrophic factor in the offspring. Additionally, S. radix maintained normal 11β-HSD1 expression in the placenta of prenatal stress mice, ensuring a normal level of glucocorticoids (GCs) and glucocorticoid receptors (GRs) in the fetus. Furthermore, S. radix increased the mRNA expression of GR and 11β-HSD2 while decreasing the mRNA expression of 11β-HSD1, thereby normalizing levels of serum CRH, ACTH, and GC in the offspring. Finally, docking results indicated that baicalein, wogonin, wogonoside, and baicalin exhibited stronger binding ability with the target.</p><p><strong>Conclusion: </strong>The results of our study indicate that S. radix may have the potential to alleviate prenatal stress-induced anxiety-like and depression-like behaviors in offspring, at least partially through protecting placental barrier function, reversing HPA axis hyperfunction, and ameliorating neurodevelopmental dysfunction.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-19"},"PeriodicalIF":2.3,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866122","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":"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":"1-18"},"PeriodicalIF":2.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pubertal- and Stress-Dependent Changes in Cellular Activation and Expression of Excitatory Amino Acid Receptor Subunits in the Paraventricular Nucleus of the Hypothalamus in Male and Female Rats.","authors":"Catherine Parkin, Juliet Ortiz, Sofia Cruz, Kevin G Bath, Russell D Romeo","doi":"10.1159/000542277","DOIUrl":"10.1159/000542277","url":null,"abstract":"<p><strong>Introduction: </strong>Pubertal maturation is marked by significant changes in stress-induced hormonal responses mediated by the hypothalamic-pituitary-adrenal (HPA) axis, with prepubertal male and female rats often exhibiting greater HPA reactivity compared to adult males and females. Though the implications of these changes are unclear, elevated stress responsiveness might contribute to the stress-related vulnerabilities often associated with puberty.</p><p><strong>Methods: </strong>The current experiments sought to determine whether differences in cellular activation, as measured by FOS immunohistochemistry, or excitatory ionotropic glutamate receptor subunit expression, as measured by qRT-PCR, in the paraventricular nucleus (PVN) were associated with these noted pubertal shifts in stress reactivity in male and female rats. As the PVN is the key nucleus responsible for activating the hormonal stress response, we predicted greater cellular activation and higher expression levels of glutamate receptor subunits in the PVN of prepubertal males and females compared to their adult counterparts.</p><p><strong>Results: </strong>Our FOS data revealed that while prepubertal males showed greater stress-induced activation in the PVN than adult males, prepubertal females showed less activation than adult females. Moreover, many of the NMDA, AMPA, and kainate receptor subunits measured, including Grin1, Grin2b, Gria1, Gria2, Grik1, and Grik2, had higher expression levels in adults, particularly in males.</p><p><strong>Conclusions: </strong>Though not supporting our initial predictions, these data do indicate that age and stress influence the activation of the PVN and the expression of glutamate receptor subunits important in its function. These data also suggest that the effects of age and stress are different in males and females. Though still far from a clear understanding of what mechanism(s) mediate pubertal shift in stress reactivity, these data add to our growing understanding of how age, stress, and sex influence HPA function.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-11"},"PeriodicalIF":2.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142523526","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":"Dexmedetomidine Alleviates the Long-Term Neurodevelopmental Toxicity Induced by Sevoflurane in the Developing Brain.","authors":"Ting-Ting Yang, Ran Wei, Fei-Fei Jin, Wei Yu, Fang Zhang, Yu Peng, Shu-Jun Zhang, Si-Hua Qi, Jia-Ren Liu","doi":"10.1159/000542114","DOIUrl":"10.1159/000542114","url":null,"abstract":"<p><strong>Introduction: </strong>Sevoflurane is an extensively used anesthetic for pediatric patients; however, numerous studies showed that sevoflurane (SEVO) may cause long-term neurodevelopmental toxicity. Dexmedetomidine (DEX) has been shown to be protective against SEVO-induced neurotoxicity, but the mechanism remains unclear. The effects and mechanisms of different DEX administration routes on SEVO-induced neurotoxicity and long-term cognitive defects were determined and further investigated the role of sex in these processes.</p><p><strong>Methods: </strong>Male and female Sprague Dawley rats at postnatal day 7 (PND7) received an intraperitoneal injection of DEX (10 μg/kg) before or after exposure to 2.5% SEVO for 6 h, or before and after SEVO exposure. The respiratory and mortality rates of the pups were recorded during anesthesia. Neuroapoptosis was evaluated by TdT-mediated dUTP nick-end labeling staining. Immunohistochemistry and immunofluorescence were employed to detect the expression of caspase-3 in neuronal cells and neurons. The expression of GSK-3β and DISC1 was determined by Western blotting or RT-qPCR. Morris water maze (MWM) test was used to evaluate the learning and memory ability of rats until they were 3 weeks and 5 weeks old.</p><p><strong>Results: </strong>Compared with the control group, exposure to 2.5% SEVO resulted in increased neuroapoptosis and decreased the expression of DISC1 at levels of mRNA and protein and phosphorylated GSK-3β in the developing brain. SEVO exposure during critical neurodevelopmental periods could cause persistent cognitive defects in adolescent male and female rats and inhibited DISC1 and phosphorylated GSK-3β protein expression. The neurotoxic impacts of SEVO were lessened by the administration of DEX (10 μg/kg) before or after exposure.</p><p><strong>Conclusion: </strong>Our findings suggest that DEX (10 μg/kg) mitigates the neurotoxic effects of SEVO on the developing rat brain as well as postnatal cognitive defects by regulating the DISC1/GSK-3β signaling.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1"},"PeriodicalIF":4.6,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479780","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 Relationship between Early Exposure to General Anesthesia and Neurobehavioral Deficits.","authors":"Jinnan Xu, Fan Wang, Yi Gao, Chuanyu Qi, Tiannan Chen, Jia Yan","doi":"10.1159/000542005","DOIUrl":"10.1159/000542005","url":null,"abstract":"<p><strong>Background: </strong>In contemporary medical practice, general anesthesia plays an essential role in pediatric surgical procedures. While modern anesthetic protocols have demonstrated safety and efficacy across various pathological conditions, concerns persist regarding the potential neurotoxic effects associated with early exposure to general anesthesia.</p><p><strong>Summary: </strong>Current research primarily examines the neurocognitive developmental impacts, with limited focus on neurobehavioral developmental disorders. This review presents a comprehensive analysis of clinical trial results related to five critical neurobehavioral developmental disorders: fine motor disability, attention-deficit hyperactivity disorder, impulse control disorders, autism spectrum disorder, and developmental coordination disorder. Furthermore, this review synthesizes insights from basic research on the potential toxicological mechanisms of general anesthetic agents that could influence clinical neurobehavioral changes. These findings provide valuable guidance for the prudent and safe utilization of anesthetic agents in pediatric patients.</p><p><strong>Key messages: </strong>This review explores the potential connections between general anesthesia and five neurobehavioral disorders, highlighting the importance of cautious anesthetic use in children in light of current research findings.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-17"},"PeriodicalIF":2.3,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479781","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":"Ultrarare Variants in DNA Damage Repair Genes in Pediatric Acute-Onset Neuropsychiatric Syndrome or Acute Behavioral Regression in Neurodevelopmental Disorders.","authors":"Janet L Cunningham, Jennifer Frankovich, Robert A Dubin, Erika Pedrosa, Refia Nur Baykara, Noelle Cathleen Schlenk, Shahina B Maqbool, Hedwig Dolstra, Jacqueline Marino, Jacob Edinger, Julia M Shea, Gonzalo Laje, Sigrid M A Swagemakers, Siamala Sinnadurai, Zhengdong D Zhang, Jhih-Rong Lin, Peter J van der Spek, Herbert M Lachman","doi":"10.1159/000541908","DOIUrl":"10.1159/000541908","url":null,"abstract":"<p><strong>Introduction: </strong>Acute onset of severe psychiatric symptoms or regression may occur in children with premorbid neurodevelopmental disorders, although typically developing children can also be affected. Infections or other stressors are likely triggers. The underlying causes are unclear, but a current hypothesis suggests the convergence of genes that influence neuronal and immunological function. We previously identified 11 genes in pediatric acute-onset neuropsychiatric syndrome (PANS), in which two classes of genes related to either synaptic function or the immune system were found. Among the latter, three affect the DNA damage response (DDR): PPM1D, CHK2, and RAG1. We now report an additional 17 cases with mutations in PPM1D and other DDR genes in patients with acute onset of psychiatric symptoms and/or regression that their clinicians classified as PANS or another inflammatory brain condition.</p><p><strong>Methods: </strong>We analyzed genetic findings obtained from parents and carried out whole-exome sequencing on a total of 17 cases, which included 3 sibling pairs and a family with 4 affected children.</p><p><strong>Results: </strong>The DDR genes include clusters affecting p53 DNA repair (PPM1D, ATM, ATR, 53BP1, and RMRP), and the Fanconi Anemia Complex (FANCE, SLX4/FANCP, FANCA, FANCI, and FANCC). We hypothesize that defects in DNA repair genes, in the context of infection or other stressors, could contribute to decompensated states through an increase in genomic instability with a concomitant accumulation of cytosolic DNA in immune cells triggering DNA sensors, such as cGAS-STING and AIM2 inflammasomes, as well as central deficits on neuroplasticity. In addition, increased senescence and defective apoptosis affecting immunological responses could be playing a role.</p><p><strong>Conclusion: </strong>These compelling preliminary findings motivate further genetic and functional characterization as the downstream impact of DDR deficits may point to novel treatment strategies.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-20"},"PeriodicalIF":2.3,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479782","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}