Exogenous Neonatal Erythropoietin Mitigates Brain Damage After a Combination of Prenatal Hypoxic-Ischemia and Lipopolysaccharide Inflammation in Rats

2008 ◽  
Vol 1 (4) ◽  
pp. A353
Author(s):  
Shenandoah Robinson ◽  
Qing Li
Keyword(s):  
Brain Damage ◽  
Intracellular Signaling ◽  
System Development ◽  
Intrauterine Infection ◽  
Artery Occlusion ◽  
Nervous System Development ◽  
Human Infants ◽  
Hypoxic Ischemia ◽  
Show Evidence ◽  
The Impact

Introduction Many infants born very preterm who suffer brain damage most likely experienced a combined insult from intrauterine infection and placental insufficiency. Damage is thought to be synergistic rather than additive but the mechanisms of combined injury remain elusive. A combination of lipopolysaccharide-induced inflammation and hypoxia-ischemia has been used in rats to model the dual insult that occurs in human infants prenatally. Erythropoietin, a pleiotrophic cytokine that is essential for central nervous system development, ameliorates brain injury after isolated hypoxic-ischemic or inflammatory insults through different intracellular signaling pathways. We hypothesized that exogenous neonatal EPO administration would lessen the damage of a combined prenatal insult in rats. Methods On embryonic Day 18 fetal rats experienced 60 minutes of transient uterine artery occlusion with or without intracervical LPS administration with sham controls receiving surgery but no occlusion and saline for LPS. Survival was recorded and histological biochemical and functional assays were performed. Means were compared with ANOVA with Tukey HSD post hoc analysis. Results After a combined insult of HI and 0.15-mg/kg LPS on E18 the survival of pups by postnatal Day 1 (P1) decreased from 77% with HI alone to 22% for LPS plus HI. When exogenous systemic EPO was administered P1–P3 survival to P9 improved markedly from 40% (2 of 5) for saline-treated insult pups to 100% (6 of 6) for EPO-treated. Initial histological analyses show EPO decreases the number of brain activated caspase 3 and activated microglia by P9. Additional analyses will be presented. Conclusion As at least 60% of placentas from infants born pre-term show evidence of chorioamnionitis, assessment of the impact of exogenous EPO on a model of a combination injury is essential prior to proceeding with a clinical trial. Initial results indicate neonatal exogenous EPO mitigates damage from the combined insult.

scholarly journals Neurotrophins as Key Regulators of Cell Metabolism: Implications for Cholesterol Homeostasis

2021 ◽  
Vol 22 (11) ◽  
pp. 5692
Author(s):  
Mayra Colardo ◽  
Noemi Martella ◽  
Daniele Pensabene ◽  
Silvia Siteni ◽  
Sabrina Di Bartolomeo ◽  
...  
Keyword(s):  
Growth Factors ◽  
Cholesterol Metabolism ◽  
System Development ◽  
Cell Metabolism ◽  
Redox Balance ◽  
Nervous System Development ◽  
Cholesterol Homeostasis ◽  
Signaling Cascades ◽  
Target Cells ◽  
The Impact

Neurotrophins constitute a family of growth factors initially characterized as predominant mediators of nervous system development, neuronal survival, regeneration and plasticity. Their biological activity is promoted by the binding of two different types of receptors, leading to the generation of multiple and variegated signaling cascades in the target cells. Increasing evidence indicates that neurotrophins are also emerging as crucial regulators of metabolic processes in both neuronal and non-neuronal cells. In this context, it has been reported that neurotrophins affect redox balance, autophagy, glucose homeostasis and energy expenditure. Additionally, the trophic support provided by these secreted factors may involve the regulation of cholesterol metabolism. In this review, we examine the neurotrophins’ signaling pathways and their effects on metabolism by critically discussing the most up-to-date information. In particular, we gather experimental evidence demonstrating the impact of these growth factors on cholesterol metabolism.

scholarly journals Role of Nuclear Receptors in Central Nervous System Development and Associated Diseases

2015 ◽  
Vol 9s2 ◽  
pp. JEN.S25480 ◽  
Author(s):  
Ana Ana Maria ◽  
Moreno-Ramos Oscar Andréas ◽  
Neena B. Haider
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Nuclear Receptors ◽  
System Development ◽  
Nuclear Hormone Receptor ◽  
Nervous System Development ◽  
Wide Range ◽  
And Function ◽  
The Impact

The nuclear hormone receptor (NHR) superfamily is composed of a wide range of receptors involved in a myriad of important biological processes, including development, growth, metabolism, and maintenance. Regulation of such wide variety of functions requires a complex system of gene regulation that includes interaction with transcription factors, chromatin-modifying complex, and the proper recognition of ligands. NHRs are able to coordinate the expression of genes in numerous pathways simultaneously. This review focuses on the role of nuclear receptors in the central nervous system and, in particular, their role in regulating the proper development and function of the brain and the eye. In addition, the review highlights the impact of mutations in NHRs on a spectrum of human diseases from autism to retinal degeneration.

scholarly journals Pre- and peri-implantation Zika virus infection impairs fetal development by targeting trophectoderm cells

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Lei Tan ◽  
Lauretta A. Lacko ◽  
Ting Zhou ◽  
Delia Tomoiaga ◽  
Romulo Hurtado ◽  
...  
Keyword(s):  
Zika Virus ◽  
System Development ◽  
Neural Progenitor Cell ◽  
Nervous System Development ◽  
Zikv Infection ◽  
Neural Lineage ◽  
Trophectoderm Cells ◽  
Increased Risk ◽  
Underlying Mechanisms ◽  
The Impact

Abstract Zika virus (ZIKV) infection results in an increased risk of spontaneous abortion and poor intrauterine growth although the underlying mechanisms remain undetermined. Little is known about the impact of ZIKV infection during the earliest stages of pregnancy, at pre- and peri-implantation, because most current ZIKV pregnancy studies have focused on post-implantation stages. Here, we demonstrate that trophectoderm cells of pre-implantation human and mouse embryos can be infected with ZIKV, and propagate virus causing neural progenitor cell death. These findings are corroborated by the dose-dependent nature of ZIKV susceptibility of hESC-derived trophectoderm cells. Single blastocyst RNA-seq reveals key transcriptional changes upon ZIKV infection, including nervous system development, prior to commitment to the neural lineage. The pregnancy rate of mice is >50% lower in pre-implantation infection than infection at E4.5, demonstrating that pre-implantation ZIKV infection leads to miscarriage. Cumulatively, these data elucidate a previously unappreciated association of pre- and peri-implantation ZIKV infection and microcephaly.

scholarly journals Coexpression Network Analysis of miRNA-142 Overexpression in Neuronal Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Ishwor Thapa ◽  
Howard S. Fox ◽  
Dhundy Bastola
Keyword(s):  
Posttranscriptional Regulation ◽  
Noncoding Rna ◽  
System Development ◽  
Neuronal Cells ◽  
Nervous System Development ◽  
Differential Analysis ◽  
Multiple Sources ◽  
Small Noncoding Rna ◽  
Meaningful Relationships ◽  
The Impact

MicroRNAs are small noncoding RNA molecules, which are differentially expressed in diverse biological processes and are also involved in the regulation of multiple genes. A number of sites in the 3′ untranslated regions (UTRs) of different mRNAs allow complimentary binding for a microRNA, leading to their posttranscriptional regulation. The miRNA-142 is one of the microRNAs overexpressed in neurons that is found to regulateSIRT1andMAOAgenes. Differential analysis of gene expression data, which is focused on identifying up- or downregulated genes, ignores many relationships between genes affected by miRNA-142 overexpression in a cell. Thus, we applied a correlation network model to identify the coexpressed genes and to study the impact of miRNA-142 overexpression on this network. Combining multiple sources of knowledge is useful to infer meaningful relationships in systems biology. We applied coexpression model on the data obtained from wild type and miR-142 overexpression neuronal cells and integrated miRNA seed sequence mapping information to identify genes greatly affected by this overexpression. Larger differences in the enriched networks revealed that the nervous system development related genes such asTEAD2, PLEKHA6, andPOGLUT1were greatly impacted due to miRNA-142 overexpression.

scholarly journals Ten-eleven translocation 1 mediated-DNA hydroxymethylation is required for myelination and remyelination in the mouse brain

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ming Zhang ◽  
Jian Wang ◽  
Kaixiang Zhang ◽  
Guozhen Lu ◽  
Yuming Liu ◽  
...  
Keyword(s):  
Mouse Brain ◽  
Intracellular Signaling ◽  
System Development ◽  
Nervous System Development ◽  
Oligodendrocyte Progenitor Cells ◽  
Calcium Activity ◽  
Dna Hydroxymethylation ◽  
Tet Proteins ◽  
A Genome

AbstractTen-eleven translocation (TET) proteins, the dioxygenase for DNA hydroxymethylation, are important players in nervous system development and diseases. However, their role in myelination and remyelination after injury remains elusive. Here, we identify a genome-wide and locus-specific DNA hydroxymethylation landscape shift during differentiation of oligodendrocyte-progenitor cells (OPC). Ablation of Tet1 results in stage-dependent defects in oligodendrocyte (OL) development and myelination in the mouse brain. The mice lacking Tet1 in the oligodendrocyte lineage develop behavioral deficiency. We also show that TET1 is required for remyelination in adulthood. Transcriptomic, genomic occupancy, and 5-hydroxymethylcytosine (5hmC) profiling reveal a critical TET1-regulated epigenetic program for oligodendrocyte differentiation that includes genes associated with myelination, cell division, and calcium transport. Tet1-deficient OPCs exhibit reduced calcium activity, increasing calcium activity rescues the differentiation defects in vitro. Deletion of a TET1-5hmC target gene, Itpr2, impairs the onset of OPC differentiation. Together, our results suggest that stage-specific TET1-mediated epigenetic programming and intracellular signaling are important for proper myelination and remyelination in mice.

scholarly journals A detailed observational study of maternal and neonatal variables affecting the thyroid-stimulating hormone levels in neonates

2021 ◽  
Vol 69 (1) ◽  
Author(s):  
N. R. Verma ◽  
G. Naik ◽  
S. Patel ◽  
P. Padhi ◽  
T. Naik ◽  
...  
Keyword(s):  
Birth Weight ◽  
Negative Correlation ◽  
Screening Program ◽  
System Development ◽  
Perinatal Period ◽  
Maternal Blood ◽  
Thyroid Stimulating Hormone ◽  
Nervous System Development ◽  
The Impact ◽  
Stimulating Hormone

Abstract Background Thyroid hormones are essential for fetal growth and the central nervous system development. Thyroid-stimulating hormone (TSH) is the key regulatory hormone. Their levels are quite dynamic in the perinatal period and are influenced by multiple factors. These factors should be taken into consideration during newborn screening. This study aimed to observe the impact of maternal and neonatal factors on neonatal TSH status. Results Neonatal TSH (nTSH) depicted a positive correlation with parity (p = 0.066) while negative correlation recorded with maternal blood haemoglobin (p = 0.007) among maternal factors. New-born length (p = 0.027) and birth weight (p < 0.001) exhibited a negative correlation with nTSH among neonatal factors. Conclusions This study concludes that among all the maternal and neonatal factors, birth weight shows the most influence on nTSH. However, the effect may be compounded by other factors. As these risk elements rarely occur singly, it is often difficult to find the exposure which confer the risk on children. These factors should be considered while interpreting the result of the screening program.

scholarly journals Retinoic acid-induced SoX3 gene expression in NT2/D1 cells is RXR homodimer-independent

2009 ◽  
Vol 61 (4) ◽  
pp. 631-638
Author(s):  
Tijana Savic ◽  
Milena Stevanovic ◽  
Gordana Nikcevic
Keyword(s):  
Gene Expression ◽  
Retinoic Acid ◽  
System Development ◽  
Neural Induction ◽  
Nervous System Development ◽  
Retinoid Receptors ◽  
Pathological Development ◽  
Gene Expression Studies ◽  
The Impact ◽  
Sox3 Gene

The Sox3/SOX3 gene is implicated in the control of nervous system development. We previously demon?strated modulation of human SOX3 gene expression during neural induction of NT2/D1 cells by retinoic acid (RA). Also, we accurately verified RXR retinoid receptors as major mediators of the effect of RA on SOX3 expression, and excluded RARs as its heterodimeric partners in RA-SOX3 signaling. Here we present evidence that activation of the SOX3 gene by RA is not RXR homodimer-dependent. The described line of SOX3 gene expression studies is valuable for future investigation of the impact that this gene has multiple aspects of normal and pathological development.

scholarly journals Long-term impact of intensive postgraduate laboratory training at the Cold Spring Harbor Neurobiology of Drosophila summer course

2018 ◽  
Author(s):  
Sarah Ly ◽  
Karla Kaun ◽  
Chi-Hon Lee ◽  
David Stewart ◽  
Stefan R. Pulver ◽  
...  
Keyword(s):  
System Development ◽  
Model Organism ◽  
Nervous System Development ◽  
Cold Spring Harbor ◽  
Development Activity ◽  
Cold Spring ◽  
Long Term Impact ◽  
High Level ◽  
The Impact ◽  
Positive Impacts

AbstractIntensive postgraduate courses provide an opportunity for junior and senior level scientists to learn concepts and techniques that will advance their training and research programs. It is commonly assumed that short intensive courses have positive impacts within fields of research; however, these assumptions are rarely tested. Here we describe the framework of a long running postgraduate summer course at Cold Spring Harbor and attempt to quantify the impact made over its history. For over three decades, the Drosophila Neurobiology: Genes, Circuits & Behavior Summer Course at Cold Spring Harbor Laboratories (CSHL) has provided participants with intense instruction on a wide variety of topics and techniques in integrative neuroscience using Drosophila as a model organism. Students are introduced to the latest approaches for studying nervous system development, activity and connectivity, as well as complex behaviors and diseases. The course has a long history of successful alumni, many of whom describe participation in the course as foundational to their training. Student surveys of recent participants indicate a high level of satisfaction, improved career outcomes, and direct impact on publications. Analysis of student success reveals that over 64% of participants obtain independent faculty positions. Further, we describe ongoing efforts to enhance diversity and encourage access to scientific research at undergraduate-focused institutions. Together, our findings suggest that laboratory-intensive postgraduate courses provide a highly effective mechanism for scientific training that has lasting positive impacts on trainees.

scholarly journals MicroExonator enables systematic discovery and quantification of microexons across mouse embryonic development

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Guillermo E. Parada ◽  
Roberto Munita ◽  
Ilias Georgakopoulos-Soares ◽  
Hugo J. R. Fernandes ◽  
Veronika R. Kedlian ◽  
...  
Keyword(s):  
Single Cell ◽  
Synapse Formation ◽  
De Novo ◽  
System Development ◽  
Axon Growth ◽  
Nervous System Development ◽  
Rna Seq ◽  
Mouse Development ◽  
Mouse Tissues ◽  
The Impact

Abstract Background Microexons, exons that are ≤ 30 nucleotides, are a highly conserved and dynamically regulated set of cassette exons. They have key roles in nervous system development and function, as evidenced by recent results demonstrating the impact of microexons on behaviour and cognition. However, microexons are often overlooked due to the difficulty of detecting them using standard RNA-seq aligners. Results Here, we present MicroExonator, a novel pipeline for reproducible de novo discovery and quantification of microexons. We process 289 RNA-seq datasets from eighteen mouse tissues corresponding to nine embryonic and postnatal stages, providing the most comprehensive survey of microexons available for mice. We detect 2984 microexons, 332 of which are differentially spliced throughout mouse embryonic brain development, including 29 that are not present in mouse transcript annotation databases. Unsupervised clustering of microexons based on their inclusion patterns segregates brain tissues by developmental time, and further analysis suggests a key function for microexons in axon growth and synapse formation. Finally, we analyse single-cell RNA-seq data from the mouse visual cortex, and for the first time, we report differential inclusion between neuronal subpopulations, suggesting that some microexons could be cell type-specific. Conclusions MicroExonator facilitates the investigation of microexons in transcriptome studies, particularly when analysing large volumes of data. As a proof of principle, we use MicroExonator to analyse a large collection of both mouse bulk and single-cell RNA-seq datasets. The analyses enabled the discovery of previously uncharacterized microexons, and our study provides a comprehensive microexon inclusion catalogue during mouse development.

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