Ana Vázquez-Ágredos, Paula Rovira, Blanca Gutiérrez, Fernando Gámiz, Milagros Gallo
{"title":"Identification of differentially expressed miRNA in the rat hippocampus during adolescence through an epigenome-wide analysis.","authors":"Ana Vázquez-Ágredos, Paula Rovira, Blanca Gutiérrez, Fernando Gámiz, Milagros Gallo","doi":"10.1159/000538168","DOIUrl":"https://doi.org/10.1159/000538168","url":null,"abstract":"<p><strong>Introduction: </strong>Epigenetic mechanisms involving microRNAs (miRNAs) play a fundamental role in many biological processes, particularly during prenatal and early postnatal development. Their role in adolescent brain development, however, has been poorly described. The present study aims to explore miRNA expression in the hippocampus during adolescence compared to adulthood in rats.</p><p><strong>Method: </strong>The brains of female and male Wistar rats were extracted and the hippocampus was freshly dissected at postnatal day 41 (adolescence) and postnatal day 98 (adulthood). An epigenome-wide analysis was conducted to identify the miRNAs significantly expressed in adolescence compared to adulthood. Additionally, target genes of such miRNAs were considered to perform an exploratory gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis.</p><p><strong>Results: </strong>We identified 16 differentially expressed miRNAs in adolescent male rats compared with adult male rats, and 4 differentially expressed miRNAs in adolescent females compared with adult females. Enrichment analysis reinforced that the target genes found are related to neurodevelopmental processes such as cell proliferation, cell migration and nervous system development.</p><p><strong>Conclusion: </strong>Our findings suggest a complex pattern of miRNA expression during adolescence, which differs from that in adulthood. The differential expression of miRNA in the hippocampus during adolescence may be associated with the late developmental changes occurring in this brain region. Furthermore, the observed sex differences in miRNA expression patterns indicate potential sexual differentiation in hippocampal development. Further comprehensive investigations are needed to elucidate the roles of miRNA in normal brain development.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140029498","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":"Septotemporal variation of information processing in the hippocampus of Fmr1 KO rat.","authors":"Leonidas J Leontiadis, Panagiotis Felemegkas, George Trompoukis, Giota Tsotsokou, Athina Miliou, Evangelia Karagianni, Pavlos Rigas, Costas Papatheodoropoulos","doi":"10.1159/000537879","DOIUrl":"https://doi.org/10.1159/000537879","url":null,"abstract":"<p><p>Introduction Fragile X messenger ribonucleoprotein (FMRP) is a protein involved in many neuronal processes in the nervous system including the modulation of synaptic transmission. Loss of FMRP produces the fragile X syndrome (FXS), a neurodevelopmental disorder affecting synaptic and neuronal function and producing cognitive impairments. However, the effects of FXS on short-term processing of synaptic inputs and neuronal outputs in the hippocampus have not yet been sufficiently clarified. Furthermore, it is not known whether dorsal and ventral hippocampus are affected similarly or not in FXS. Method We used a Fmr1 knock-out (KO) rat model of FXS and recordings of evoked field potentials from the CA1 field of transverse slices from both the dorsal and the ventral hippocampus of adult rats. Results Following application of a frequency stimulation protocol consisting of a ten-pulse train and recordings of fEPSP, we found that the dorsal but not ventral KO hippocampus shows altered short-term synaptic plasticity. Furthermore, applying the frequency stimulation protocol and recordings of population spikes, both segments of the KO hippocampus display altered short-term neuronal dynamics. Conclusions These data suggest that short-term processing of synaptic inputs is affected in the dorsal, not ventral FXS hippocampus, while short-term processing of neuronal output is affected in both segments of the FXS hippocampus in a similar way. These FXS-associated changes may have significant impact on the functions of the dorsal and ventral hippocampus in individuals with FXS.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139900732","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}
Ane Goikolea-Vives, Cathy Fernandes, Michael S C Thomas, Claire Thornton, Helen B Stolp
{"title":"Sex-specific behavioural deficits in adulthood following acute activation of the GABAA receptor in the neonatal mouse.","authors":"Ane Goikolea-Vives, Cathy Fernandes, Michael S C Thomas, Claire Thornton, Helen B Stolp","doi":"10.1159/000536641","DOIUrl":"10.1159/000536641","url":null,"abstract":"<p><strong>Introduction: </strong>Sex differences exist in the prevalence of neurodevelopmental disorders (NDDs). Part of the aetiology of NDDs has been proposed to be alterations in the balance between excitatory and inhibitory neurotransmission, leading to the question of whether males and females respond differently to altered neurotransmitter balance. We investigated whether pharmacological alteration of GABAA signalling in early development results in sex-dependent changes in adult behaviours associated with NDDs.</p><p><strong>Methods: </strong>Male and female C57BL/6J mice received intraperitoneal injections of 0.5mg/kg muscimol or saline on postnatal days (P) 3-5 and were subjected to behavioural testing, specifically open field, light dark box, marble burying, sucralose preference, social interaction and olfactory habituation/dishabituation tests between P60-90.</p><p><strong>Results: </strong>Early postnatal administration of muscimol resulted in reduced anxiety in the light dark box test in both male and female adult mice. Muscimol reduced sucralose preference in males, but not females, whereas female mice showed reduced social behaviours. Regional alterations in cortical thickness were observed in the weeks following GABAA receptor activation, pointing to an evolving structural difference in the brain underlying adult behaviour.</p><p><strong>Conclusions: </strong>We conclude that activation of the GABAA receptor in the first week of life resulted in long-lasting changes in a range of behaviours in adulthood following altered neurodevelopment. Sex of the individual affected the nature and severity of these abnormalities, explaining part of the varied pathophysiology and neurodevelopmental diagnosis that derive from excitatory/inhibitory imbalance.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139703904","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}
Kelsey Christoffel, Josepheen De Asis-Cruz, Rathinaswamy B Govindan, Jung Hoon Kim, Kevin Michael Cook, Kushal Kapse, Nickie Andescavage, Sudeepta Basu, Emma Spoehr, Catherine Limperopoulos, Adre Du Plessis
{"title":"Central Autonomic Network and heart rate variability in premature neonates.","authors":"Kelsey Christoffel, Josepheen De Asis-Cruz, Rathinaswamy B Govindan, Jung Hoon Kim, Kevin Michael Cook, Kushal Kapse, Nickie Andescavage, Sudeepta Basu, Emma Spoehr, Catherine Limperopoulos, Adre Du Plessis","doi":"10.1159/000536513","DOIUrl":"10.1159/000536513","url":null,"abstract":"<p><strong>Introduction: </strong>The Central Autonomic Network (CAN) is a hierarchy of brain structures that collectively influence cardiac autonomic input, mediating the majority of brain-heart interactions, but has never been studied in premature neonates. In this study, we use heart rate variability (HRV), which has been described as the \"primary output\" of the CAN, and resting state functional MRI to characterize brain-heart relationships in premature neonates.</p><p><strong>Methods: </strong>We studied premature neonates who underwent resting state functional MRI (rsfMRI) at term, (37-weeks postmenstrual age [PMA] or above) and had HRV data recorded during the same week of their MRI. HRV was derived from continuous electrocardiogram data during the week of the rsfMRI scan. For rsfMRI, a seed-based approach was used to define regions of interest (ROI) pertinent to the CAN, and blood oxygen level-dependent signal was correlated between each ROI as a measure of functional connectivity. HRV was correlated with CAN connectivity (CANconn) for each region, and sub-group analysis was performed based on sex and clinical comorbidities.</p><p><strong>Results: </strong>Forty-seven premature neonates were included in this study, with a mean gestational age at birth of 28.1 +/- 2.6 weeks. Term CANconn was found to be significantly correlated with HRV in approximately one-fifth of CAN connections. Two distinct patterns emerged among these HRV-CANconn relationships. In the first, increased HRV was associated with stronger CANconn of limbic regions. In the second pattern, stronger CANconn at the precuneus was associated with impaired HRV maturation. These patterns were especially pronounced in male premature neonates.</p><p><strong>Conclusion: </strong>We report for the first time evidence of brain-heart relationships in premature neonates and an emerging CAN, most striking in male neonates, suggesting that the brain-heart axis may be more vulnerable in male premature neonates. Signatures in the heart rate may eventually become an important non-invasive tool to identify premature males at highest risk for neurodevelopmental impairment.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11300706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139698817","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":"Early Gray Matter Structural Covariance Predicts Longitudinal Gain in Arithmetic Ability in Children.","authors":"Tian Ren, Zheng Li, Chunjie Wang, Bao-Ming Li","doi":"10.1159/000531419","DOIUrl":"10.1159/000531419","url":null,"abstract":"<p><p>Previous neuroimaging studies on arithmetic development have mainly focused on functional activation or functional connectivity between brain regions. It remains largely unknown how brain structures support arithmetic development. The present study investigated whether early gray matter structural covariance contributes to later gain in arithmetic ability in children. We used a public longitudinal sample comprising 63 typically developing children. The participants received structural magnetic resonance imaging scanning when they were 11 years old and were tested with a multiplication task at 11 years old (time 1) and 13 years old (time 2), respectively. Mean gray matter volumes were extracted from eight brain regions of interest to anchor salience network (SN), frontal-parietal network (FPN), motor network (MN), and default mode network (DMN) at time 1. We found that longitudinal gain in arithmetic ability was associated with stronger structural covariance of the SN seed with frontal and parietal regions and stronger structural covariance of the FPN seed with insula, but weaker structural covariance of the FPN seed with motor and temporal regions, weaker structural covariance of the MN seed with frontal and motor regions, and weaker structural covariance of the DMN seed with temporal region. However, we did not detect correlation between longitudinal gain in arithmetic ability and behavioral measure or regional gray matter volume at time 1. Our study provides novel evidence for a specific contribution of gray matter structural covariance to longitudinal gain in arithmetic ability in childhood.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"119-135"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9583143","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":"MYC Promotes Aggressive Growth and Metastasis of a WNT-Medulloblastoma Mouse Model.","authors":"Rachel Hartley, Timothy N Phoenix","doi":"10.1159/000533270","DOIUrl":"10.1159/000533270","url":null,"abstract":"<p><p>Medulloblastoma (MB), the most common malignant pediatric brain tumor, comprises four molecularly and clinically distinct subgroups (termed WNT, SHH, group 3, and group 4). Prognosis varies based on genetic and pathological features associated with each molecular subgroup. WNT-MB, considered low-risk, is rarely metastatic and contains activating mutations in CTNNB1; group 3-MB (GRP3-MB), commonly classified as high-risk, is frequently metastatic and can contain genomic alterations, resulting in elevated MYC expression. Here, we compare model systems of low-risk WNT-MB and high-risk GRP3-MB to identify tumor and microenvironment interactions that could contribute to features associated with prognosis. Compared to GRP3-MB, we find that WNT-MB is enriched in gene sets related to extracellular matrix (ECM) regulation and cellular adhesion. Exogenous expression of MycT58A in a murine WNT-MB model significantly accelerates growth and results in metastatic disease. In addition to decreased ECM regulation and cell adhesion pathways, we also identified immune system interactions among the top downregulated signaling pathways following MycT58A expression. Taken together, our data provide evidence that increased Myc signaling can promote the growth and metastasis in a murine model of WNT-MB.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"167-178"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9949091","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":"Expression Analyses of C-Terminal-Binding Protein 1 (CtBP1) during Mouse Brain Development.","authors":"Nanako Hamada, Tohru Matsuki, Ikuko Iwamoto, Takuma Nishijo, Mariko Noda, Hidenori Tabata, Atsuo Nakayama, Koh-Ichi Nagata","doi":"10.1159/000534886","DOIUrl":"10.1159/000534886","url":null,"abstract":"<p><strong>Introduction: </strong>C-terminal-binding protein 1 (CtBP1) is a multi-functional protein with well-established roles as a transcriptional co-repressor in the nucleus and a regulator of membrane fission in the cytoplasm. Although CtBP1 gene abnormalities have been reported to cause neurodevelopmental disorders, the physiological role and expression profile of CtBP1 remains to be elucidated.</p><p><strong>Methods: </strong>In this study, we used biochemical, immunohistochemical, and immunofluorescence methods to analyze the expression of CtBP1 during mouse brain development.</p><p><strong>Results: </strong>Western blotting analyses revealed that CtBP1 appeared to be expressed mainly in the central nervous system throughout the developmental process. In immunohistochemical analyses, region-specific nuclear as well as weak cytoplasmic distribution of CtBP1 was observed in telencephalon at embryonic day (E)15 and E17. It is of note that CtBP1 was barely detected in axons but observed in the nucleus of oligodendrocytes in the white matter at E17. As to the cerebellum at postnatal day 30, CtBP1 appeared to be expressed in the nucleus and cytoplasm of Purkinje cells, the nucleus of granule cells and cells in the molecular layer (ML), and the ML per se, where granule cell axons and Purkinje cell dendrites are enriched. In addition, CtBP1 was detected in the cerebellar nuclei.</p><p><strong>Conclusion: </strong>The obtained results suggest involvement of CtBP1 in brain function.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"262-272"},"PeriodicalIF":2.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71428703","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":"My Life with Verne.","authors":"Richard S Nowakowski","doi":"10.1159/000531759","DOIUrl":"10.1159/000531759","url":null,"abstract":"","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"153-157"},"PeriodicalIF":2.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9748025","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":"Fetal Origins of Health Disparities: Transgenerational Consequences of Racism.","authors":"Nana Matoba, James W Collins, Maria L V Dizon","doi":"10.1159/000531462","DOIUrl":"10.1159/000531462","url":null,"abstract":"<p><p>Despite advances in perinatal medicine, racial disparity in birth outcomes remains a public health problem in the USA. The underlying mechanisms for this long-standing racial disparity are incompletely understood. This review presents transgenerational risk factors for racial disparities in preterm birth, exploring the impact of interpersonal and structural racism, theoretical models of stress, and biological markers of racial disparities.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"112-118"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9598918","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}
Alexandra Hochstetler, George Price, Amy Baohan, Melissa Li, Frances Rodriguez Lara, Josephine Lok, Beth Costine-Bartell
{"title":"Developmental Regulation of Matrix Metalloproteinases in Response to Multifactorial, Severe Traumatic Brain Injuries during Immaturity.","authors":"Alexandra Hochstetler, George Price, Amy Baohan, Melissa Li, Frances Rodriguez Lara, Josephine Lok, Beth Costine-Bartell","doi":"10.1159/000536054","DOIUrl":"10.1159/000536054","url":null,"abstract":"<p><strong>Introduction: </strong>A striking pattern in young children after severe TBI is when the entire cortical ribbon displays tissue damage: hemispheric hypodensity (HH). HH is often a result of abusive head trauma (AHT). We previously reported a model of HH in a gyrencephalic species where a combination of injuries consisting of (1) cortical impact, (2) midline shift, (3) subdural hematoma/subarachnoid hemorrhage, (4) traumatic seizures, and (5) brief apnea and hypoventilation resulted in extensive, hypoxic-ischemic-type injury. Importantly, this mechanism closely resembles that seen in children, with relative sparing of the contralateral cortex, thus ruling out a pure asphyxia mechanism. In this model, piglets of similar developmental stage to human toddlers (postnatal day 30, PND30) have extensive hypoxic-ischemic damage to the cortical ribbon with sparing of the contralateral hemisphere and deep gray matter areas. However, piglets of similar developmental stage to human infants (postnatal day 7, PND7) have less hypoxic-ischemic damage that is notably bilateral and patchy. We therefore sought to discover whether the extensive tissue damage observed in PND30 was due to a greater upregulation of matrix metalloproteinases (MMPs).</p><p><strong>Materials and methods: </strong>In PND7 or PND30 piglets receiving AHT injuries (cortical impact, midline shift, subdural hematoma/subarachnoid hemorrhage, traumatic seizures, and brief apnea and hypoventilation) or a sham injury, the pattern of albumin extravasation and MMP-9 upregulation throughout the brain was determined via immunohistochemistry, brain tissue adjacent to the cortical impact where the tissue damage spreads was collected for Western blots, and the gelatinase activity was determined over time in peripheral plasma. EEG was recorded, and piglets survived up to 24 h after injury administration.</p><p><strong>Results: </strong>The pattern of albumin extravasation, indicating vasogenic edema, as well as increase in MMP-9, were both present at the same areas of hypoxic-ischemic tissue damage. Evidence from immunohistochemistry, Western blot, and zymogens demonstrate that MMP-2, -3, or -9 are constitutively expressed during immaturity and are not different between developmental stages; however, active forms are upregulated in PND30 but not PND7 after in response to AHT model injuries. Furthermore, peripheral active MMP-9 was downregulated after model injuries in PND7.</p><p><strong>Conclusions: </strong>This differential response to AHT model injuries might confer protection to the PND7 brain. Additionally, we find that immature gyrencephalic species have a greater baseline and array of MMPs than previously demonstrated in rodent species. Treatment with an oral or intravenous broad-spectrum matrix metalloproteinase inhibitor might reduce the extensive spread of injury in PND30, but the exposure to metalloproteinase inhibitors must be acute as to not interfere with the homeostatic role of ma","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"319-332"},"PeriodicalIF":2.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11228128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139405092","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}