Developmental Neuroscience最新文献

{"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":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p><p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p><p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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":2.3,"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":"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":"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":2.3,"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":"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":"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":"206-216"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12034827/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dendritic Morphology of Developing Hippocampal Neurons in Cyp11a1 Null Mice.","authors":"Hao-Hua Jiang, Tzu-Hsuan Wu, Li-Jen Lee, Jui-Chen Lee, Bon-Chu Chung, Feng-Ming Yang, Meng-Chun Hu","doi":"10.1159/000540106","DOIUrl":"10.1159/000540106","url":null,"abstract":"<p><strong>Introduction: </strong>Neurosteroids have a variety of neurological functions, such as neurite growth, neuroprotection, myelination, and neurogenesis. P450scc, encoded by CYP11A1 gene, is the cholesterol side chain cleavage enzyme that catalyzes the first and rate-limiting step in steroidogenesis. In this study, we examine the dendritic morphology in developing hippocampal neurons of Cyp11a1 null mice at P15, a critical period for synapse formation and maturation.</p><p><strong>Methods: </strong>Knockout mice were maintained until P15 with hormone administration. The Golgi-Cox method stained CA1 and CA3 pyramidal neurons in the hippocampus to reveal dendritic morphology.</p><p><strong>Results: </strong>We demonstrated that Cyp11a1 null mice usually die within 7 days after birth and thus collected brain samples at postnatal day 5 (P5) for examination. There was significant shrinkage of dendrite size and diminishment of dendritic branching in CA1 and CA3 pyramidal neurons in the hippocampus of Cyp11a1 null mice, suggesting a developmental delay. We wonder if this delay may catch up later in life. Since the age of P15 is a critical period for synapse formation and maturation, the Cyp11a1 null mice were rescued by receiving hormone administration until P15 that the dendritic morphology in the developing hippocampal neurons could be examined. The results indicated that the total dendritic length, the number of dendritic branches, as well as dendritic arborization in the CA1 and CA3 pyramidal neurons are significantly decreased in P15 knockout mice when compared to the wild type. The spine densities were also significantly decreased. In addition, the Western blot analysis revealed decreased PSD-95 expression levels in the knockout mice compared to the wild type at P15.</p><p><strong>Conclusion: </strong>These results suggested that Cyp11a1 deficiency impairs the dendritic structures in the developing hippocampal pyramidal neurons.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"157-171"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12140598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141494121","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":"Protective Effects of Early Neonatal Methylxanthine Treatment on Cognitive and Language Outcomes in Premature Infants with and without High-Risk Perinatal Factors.","authors":"Ruth M McLeod, Ted S Rosenkrantz, R Holly Fitch","doi":"10.1159/000540540","DOIUrl":"10.1159/000540540","url":null,"abstract":"<p><strong>Introduction: </strong>Caffeine and theophylline are methylxanthines and nonselective adenosine antagonists commonly used to treat apnea of prematurity. Both human and animal data suggest that xanthines also have clinically important long-term neuroprotective effects in the presence of inflammation in the perinatal period as seen following hypoxic-ischemic brain insults. Moreover, these protective effects appear to be more robust when administered shortly (<48 h) after preterm birth.</p><p><strong>Method: </strong>To evaluate the importance of the postdelivery therapeutic window, we collected and analyzed medical data from preterm infants meeting criteria (23-30 weeks' gestational age [GA]), born at the University of Connecticut Health Center (UCHC), and cared for at the UCHC/Connecticut Children's Medical Center (CCMC) NICU from 1991 to 2017 (n = 858). Eighteen-month follow-up data included cognitive and language scores from the Neonatal Neurodevelopmental Follow-Up Clinic records, with a retention of 81% of subjects (n = 696). Differences were analyzed via multivariate ANOVA and ANCOVA.</p><p><strong>Results: </strong>Analyses showed that infants who received xanthine treatment within the first 48 h after preterm birth showed significantly better 18-month behavioral outcomes than those treated later than 48 h, despite a lack of a priori differences in GA, birth, or length of stay. The positive effect of early xanthine therapy was particularly robust for infants exposed prenatally to the inflammatory conditions of chorioamnionitis and/or preeclampsia.</p><p><strong>Conclusions: </strong>Current findings are consistent with human and animal data, showing that caffeine exerts protective effects, at least in part via attenuation of inflammation. Results add to the evidence supporting routine immediate prophylactic neuroprotective xanthine therapy (i.e., caffeine) in preterm infants. Findings also add important new evidence of the augmented value of caffeine for infants with inflammatory exposure due to mothers with preeclampsia or chorioamnionitis.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"172-182"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12140599/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141762361","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":"Histone Lysine Crotonylation Associated Epigenetic Mechanism Dynamically Regulates Prenatal Stress Induced Anxiety-Related Behaviour in Adolescent Offspring.","authors":"Karunanithi Sivasangari, Koilmani Emmanuvel Rajan","doi":"10.1159/000543696","DOIUrl":"10.1159/000543696","url":null,"abstract":"<p><strong>Introduction: </strong>This study was designed to examine whether social/environmental experiences can induce the epigenetic modification, and influence the associated physiology and behaviour. To test this, we have used social stress (prenatal stress [PNS]) model and then housed at environmental enrichment (EE) condition to evaluate the interaction between specific epigenetic modification and its influence on behaviour.</p><p><strong>Methods: </strong>Pregnant rats were randomly divided into a control group, PNS group, and PNS+EE group. PNS and PNS+EE animals were subjected to social defeat stress during their gestational day (GD) 16-18. PNS animals and their offspring were always housed in standard laboratory condition, PNS+EE animal was housed in EE cage during GD-10 to the pup's age of postnatal day 30. Animals were tested for anxiety-like behaviour using open-field test (OFT) and memory was examined by passive avoidance test. Western blotting was used to detect the expression pattern of molecules associated with histone crotonylation.</p><p><strong>Result: </strong>We observed anxiety-like behaviour, memory deficit in the animals experienced PNS. Further, level of methyl-CpG binding protein-2 (MeCP2), repressor element-1 silencing transcription factor (REST), sirtuin 1(SIRT1), chromodomain Y-like and enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) and histone methylation (H3K27me3) was elevated. Whereas, the expression of p300, histone crotonylation (H3K18Cr), and neuropeptide VGF were suppressed. Notably, EE restores the normal expression pattern of MeCP2, REST, P300, SIRT1, CYDL, EZH2, H3K27me3, H3K18Cr, and VGF.</p><p><strong>Conclusion: </strong>EE reverses the PNS induced alterations, including suppression of histone crotonylation (H3K18Cr), which possibly involved in the regulation of expression of VGF and behaviour.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"217-228"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025455","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":"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":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;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?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;The weighted score was amenable to statistical manipulation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;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?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;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}