scholarly journals Neonatal Salivary Analysis Reveals Global Developmental Gene Expression Changes in the Premature Infant

2010 ◽  
Vol 56 (3) ◽  
pp. 409-416 ◽  
Author(s):  
Jill L Maron ◽  
Kirby L Johnson ◽  
David M Rocke ◽  
Michael G Cohen ◽  
Albert J Liley ◽  
...  
Keyword(s):  
Gene Expression ◽  
System Development ◽  
Newborn Care ◽  
Genomic Analysis ◽  
Nervous System Development ◽  
Comparative Genomic ◽  
Tissue Development ◽  
Bioinformatics Analyses ◽  
Noninvasive Technique ◽  
And Function

Abstract Background: There is an important need to develop noninvasive biomarkers to detect disease in premature neonates. Our objective was to determine if salivary genomic analysis provides novel information about neonatal expression of developmental genes. Methods: Saliva (50–200 μL) was prospectively collected from 5 premature infants at 5 time points: before, starting, and advancing enteral nutrition; at the introduction of oral feeds; and at advanced oral feeds. Salivary RNA was extracted, amplified, and hybridized onto whole-genomic microarrays. Results: Bioinformatics analyses identified 9286 gene transcripts with statistically significant gene expression changes across individuals over time. Of these genes, 3522 (37.9%) were downregulated, and 5764 (62.1%) were upregulated. Gene expression changes were highly associated with developmental pathways. Significantly downregulated expression was seen in embryonic development, connective tissue development and function, hematologic system development and function, and survival of the organism (10−14 < P < 10−3). Conversely, genes associated with behavior, nervous system development, tissue development, organ development, and digestive system development were significantly upregulated (10−11 < P < 10−2). Conclusions: Comparative genomic salivary analyses provide robust, comprehensive, real-time information regarding nearly all organs and tissues in the developing preterm infant. This innovative and noninvasive technique represents a new approach for monitoring health, disease, and development in this vulnerable patient population. By comparing these data in healthy infants with data from infants who develop medical complications, we expect to identify new biomarkers that will ultimately improve newborn care.

scholarly journals Dynamics of neurotransmitter and extracellular vesicle-derived microRNA landscapes during heroin and methamphetamine withdrawal

2021 ◽  
Author(s):  
Juehua Yu ◽  
Fengrong Chen ◽  
Yu Xu ◽  
Kai Shi ◽  
Zunyue Zhang ◽  
...  
Keyword(s):  
Neuronal Development ◽  
System Development ◽  
Extracellular Vesicle ◽  
Neuronal Model ◽  
Nervous System Development ◽  
Bioinformatics Analyses ◽  
Cross Sectional ◽  
And Function ◽  
Substance Withdrawal

AbstractCirculating miRNAs in small vesicles known as exosomes within blood have been emerging as a new research hotspot in the field of psychiatric disorders. The aim of this work was to characterize the changes in exosomal microRNA profiles, both short-term and long-term, during substance withdrawal using a cross-sectional study design. Using weighted gene co-expression network analysis, a series of known, conserved, and novel exosomal microRNAs were identified as being associated with withdrawal stage and key neurotransmitters GABA, choline, and serotonin. Bioinformatics analyses established that the differences in the miRNA profile target signaling pathways are associated with developmental and intellectual abnormalities. Notably, a set of dysregulated microRNA signatures including hsa-mia-451a and hsa-mir-21a resulted in an AUC of 0.966 and 0.861, respectively, for predicting patients with substance use disorders. Furthermore, hsa-miR-744a-5p was positively correlated with serotonin, and its important role in maintaining neuronal development and function was revealed using an in vitro human induced pluripotent stem cells derived neuronal model. Taken together, these data suggest that the microRNA content of circulating exosomes represent a biomolecular “fingerprint” of the progression of substance withdrawal and may uncover the putative mechanism of how these exosomal microRNAs contribute to central nervous system development and function.

Transcriptional profiling of iPSC-derived neurons with reciprocal monogenic CNV in 3p26.3 region

2020 ◽  
pp. 10-11
Author(s):  
М.Е. Лопаткина ◽  
В.С. Фишман ◽  
М.М. Гридина ◽  
Н.А. Скрябин ◽  
Т.В. Никитина ◽  
...  
Keyword(s):  
Gene Expression ◽  
Copy Number ◽  
System Development ◽  
Transcriptional Profiling ◽  
Global Gene Expression ◽  
Nervous System Development ◽  
Number Variation ◽  
The Central Nervous System ◽  
Cntn6 Gene ◽  
Copy Number Changes

Проведен анализ генной экспрессии в нейронах, дифференцированных из индуцированных плюрипотентных стволовых клеток пациентов с идиопатическими интеллектуальными нарушениями и реципрокными хромосомными мутациями в регионе 3p26.3, затрагивающими единственный ген CNTN6. Для нейронов с различным типом хромосомных аберраций была показана глобальная дисрегуляция генной экспрессии. В нейронах с вариациями числа копий гена CNTN6 была снижена экспрессия генов, продукты которых вовлечены в процессы развития центральной нервной системы. The gene expression analysis of iPSC-derived neurons, obtained from patients with idiopathic intellectual disability and reciprocal microdeletion and microduplication in 3p26.3 region affecting the single CNTN6 gene was performed. The global gene expression dysregulation was demonstrated for cells with CNTN6 copy number variation. Gene expression in neurons with CNTN6 copy number changes was downregulated for genes, whose products are involved in the central nervous system development.

scholarly journals Neurons interact with the microbiome: an evolutionary-informed perspective

Neuroforum ◽  
2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Christoph Giez ◽  
Alexander Klimovich ◽  
Thomas C. G. Bosch
Keyword(s):  
Nervous System ◽  
Neural Circuits ◽  
Current Knowledge ◽  
System Development ◽  
Nervous System Development ◽  
Comprehensive Understanding ◽  
Strategic Model ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
And Function

Abstract Animals have evolved within the framework of microbes and are constantly exposed to diverse microbiota. Microbes colonize most, if not all, animal epithelia and influence the activity of many organs, including the nervous system. Therefore, any consideration on nervous system development and function in the absence of the recognition of microbes will be incomplete. Here, we review the current knowledge on the nervous systems of Hydra and its role in the host–microbiome communication. We show that recent advances in molecular and imaging methods are allowing a comprehensive understanding of the capacity of such a seemingly simple nervous system in the context of the metaorganism. We propose that the development, function and evolution of neural circuits must be considered in the context of host–microbe interactions and present Hydra as a strategic model system with great basic and translational relevance for neuroscience.

Endocannabinoid signals in the developmental programming of delayed-onset neuropsychiatric and metabolic illnesses

2013 ◽  
Vol 41 (6) ◽  
pp. 1569-1576 ◽  
Author(s):  
Erik Keimpema ◽  
Daniela Calvigioni ◽  
Tibor Harkany
Keyword(s):  
Prescription Drugs ◽  
Maternal Nutrition ◽  
System Development ◽  
Nervous System Development ◽  
Molecular Evidence ◽  
Critical Periods ◽  
Affected Offspring ◽  
Neuropsychiatric Diseases ◽  
Maternal Programming ◽  
And Function

It is increasingly recognized that maternal exposure to metabolic (nutritional) stimuli, infections, illicit or prescription drugs and environmental stressors during pregnancy can predispose affected offspring to developing devastating postnatal illnesses. If detrimental maternal stimuli coincide with critical periods of tissue production and organogenesis then they can permanently derail key cellular differentiation programs. Maternal programming can thus either provoke developmental failure directly (‘direct hit’) or introduce latent developmental errors that enable otherwise sub-threshold secondary stressors to manifest as disease (‘double hit’) postnatally. Accumulating evidence suggests that nervous system development is tightly controlled by maternal metabolic stimuli, and whose synaptic wiring and integrative capacity are adversely affected by dietary and hormonal challenges, infections or episodes of illicit drug use. Endocannabinoids, a family of signal lipids derived from polyunsaturated fatty acids, have been implicated in neuronal fate determination, the control of axonal growth, synaptogenesis and synaptic neurotransmission. Therefore the continuum and interdependence of endocannabinoid actions during the formation and function of synapses together with dynamic changes in focal and circulating endocannabinoid levels upon maternal nutritional imbalance suggest that endocannabinoids can execute the ‘reprogramming’ of specific neuronal networks. In the present paper, we review molecular evidence suggesting that maternal nutrition and metabolism during pregnancy can affect the formation and function of the hippocampus and hypothalamus by altering endocannabinoid signalling such that neuropsychiatric diseases and obesity respectively ensue in affected offspring. Moreover, we propose that the placenta, fetal adipose and nervous tissues interact via endocannabinoid signals. Thus endocannabinoids are hypothesized to act as a molecular substrate of maternal programming.

scholarly journals Cell-to-Cell Communication in Learning and Memory: From Neuro- and Glio-Transmission to Information Exchange Mediated by Extracellular Vesicles

2019 ◽  
Vol 21 (1) ◽  
pp. 266 ◽  
Author(s):  
Gabriella Schiera ◽  
Carlo Maria Di Liegro ◽  
Italia Di Liegro
Keyword(s):  
Learning And Memory ◽  
Extracellular Vesicles ◽  
Glial Cells ◽  
Information Exchange ◽  
System Development ◽  
Cell Communication ◽  
Nervous System Development ◽  
The Body ◽  
Pathological Conditions ◽  
And Function

Most aspects of nervous system development and function rely on the continuous crosstalk between neurons and the variegated universe of non-neuronal cells surrounding them. The most extraordinary property of this cellular community is its ability to undergo adaptive modifications in response to environmental cues originating from inside or outside the body. Such ability, known as neuronal plasticity, allows long-lasting modifications of the strength, composition and efficacy of the connections between neurons, which constitutes the biochemical base for learning and memory. Nerve cells communicate with each other through both wiring (synaptic) and volume transmission of signals. It is by now clear that glial cells, and in particular astrocytes, also play critical roles in both modes by releasing different kinds of molecules (e.g., D-serine secreted by astrocytes). On the other hand, neurons produce factors that can regulate the activity of glial cells, including their ability to release regulatory molecules. In the last fifteen years it has been demonstrated that both neurons and glial cells release extracellular vesicles (EVs) of different kinds, both in physiologic and pathological conditions. Here we discuss the possible involvement of EVs in the events underlying learning and memory, in both physiologic and pathological conditions.

Serotonergic gene variation: implications for personality traits and psychopathology

1999 ◽  
Vol 11 (2) ◽  
pp. 57-59
Author(s):  
K.P. Lesch
Keyword(s):  
Complex Traits ◽  
System Development ◽  
Brain Regions ◽  
Nervous System Development ◽  
Gene Variation ◽  
Serotonergic Activity ◽  
Neural Communication ◽  
Important Regulator ◽  
And Function ◽  
Master Control

Serotonin 5-hydroxytryptamine (5-HT) is an important regulator of morphogenetic activities during early central nervous system development, including cell proliferation, migration, and differentiation as well as synapto-genesis. Serotonergic raphe neurons diffusely project to a variety of brain regions (e.g. cortex, amygdala, hippocampus) and play known roles in integrating emotion, cognition, motor function as well as in food intake, sleep, pain, and sexual activity. The diversity of physiologic functions is due to the fact that 5-HT acts as a master control neurotransmitter within a highly complex system of neural communication mediated by multiple pre- and postsynaptic 5-HT receptors, thus orchestrating the activity and interaction of several other neurotransmitter systems. Since proteins involved in the regulation of central serotonergic activity (e.g. enzymes, receptors, transporter) play pivotal role in brain 5-HT homeostasis, polymorphisms in the regulatory regions of their genes resulting in variation of expression and function are likely to influence complex traits, such as temperament/personality and psychopathology.

scholarly journals A loss-of-function homozygous mutation in DDX59 implicates a conserved DEAD-box RNA helicase in nervous system development and function

2017 ◽  
Vol 39 (2) ◽  
pp. 187-192 ◽  
Author(s):  
Vincenzo Salpietro ◽  
Stephanie Efthymiou ◽  
Andreea Manole ◽  
Bhawana Maurya ◽  
Sarah Wiethoff ◽  
...  
Keyword(s):  
Nervous System ◽  
System Development ◽  
Rna Helicase ◽  
Nervous System Development ◽  
Homozygous Mutation ◽  
Loss Of Function ◽  
Dead Box ◽  
And Function

scholarly journals Testing algorithm for identification of patients with TRK fusion cancer

2019 ◽  
Vol 72 (7) ◽  
pp. 460-467 ◽  
Author(s):  
Frédérique Penault-Llorca ◽  
Erin R Rudzinski ◽  
Antonia R Sepulveda
Keyword(s):  
Kinase Inhibitors ◽  
System Development ◽  
In Situ Hybridisation ◽  
Nervous System Development ◽  
Diagnostic Process ◽  
Fluorescence In Situ Hybridisation ◽  
Gene Fusions ◽  
Paediatric Tumours ◽  
Testing Algorithm ◽  
And Function

The neurotrophic tyrosine receptor kinase (NTRK) gene family encodes three tropomyosin receptor kinases (TRKA, TRKB, TRKC) that contribute to central and peripheral nervous system development and function. NTRK gene fusions are oncogenic drivers of various adult and paediatric tumours. Several methods have been used to detect NTRK gene fusions including immunohistochemistry, fluorescence in situ hybridisation, reverse transcriptase polymerase chain reaction, and DNA- or RNA-based next-generation sequencing. For patients with TRK fusion cancer, TRK inhibition is an important therapeutic target. Following the FDA approval of the selective TRK inhibitor, larotrectinib, as well as the ongoing development of multi-kinase inhibitors with activity in TRK fusion cancer, testing for NTRK gene fusions should become part of the standard diagnostic process. In this review we discuss the biology of NTRK gene fusions, and we present a testing algorithm to aid detection of these gene fusions in clinical practice and guide treatment decisions.

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