Non-coding RNAs in Nervous System Development and Disease

There is a growing appreciation of the role of non-coding RNAs in the regulation of gene and protein expression. Long non-coding RNAs can modulate splicing by hybridizing with precursor messenger RNAs (pre-mRNAs) and influence RNA editing, mRNA stability, translation activation and microRNA-mRNA interactions by binding to mature mRNAs. LncRNAs are highly abundant in the brain and have been implicated in neurodevelopmental disorders. Long intergenic non-coding RNAs are the largest subclass of lncRNAs and play a crucial role in gene regulation. We used RNA sequencing and bioinformatic analyses to identify lincRNAs and their predicted mRNA targets associated with fear extinction that was induced by intra-hippocampally administered D-cycloserine in an animal model investigating the core phenotypes of PTSD. We identified 43 differentially expressed fear extinction related lincRNAs and 190 differentially expressed fear extinction related mRNAs. Eight of these lincRNAs were predicted to interact with and regulate 108 of these mRNAs and seven lincRNAs were predicted to interact with 22 of their pre-mRNA transcripts. On the basis of the functions of their target RNAs, we inferred that these lincRNAs bind to nucleotides, ribonucleotides and proteins and subsequently influence nervous system development, and morphology, immune system functioning, and are associated with nervous system and mental health disorders. Quantitative trait loci that overlapped with fear extinction related lincRNAs, included serum corticosterone level, neuroinflammation, anxiety, stress and despair related responses. This is the first study to identify lincRNAs and their RNA targets with a putative role in transcriptional regulation during fear extinction.

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Identification and functional analysis of long non-coding RNAs in autism spectrum disorders

10.1101/2020.03.15.986497 ◽

2020 ◽

Author(s):

Zhan Tong ◽

Yuan Zhou ◽

Juan Wang

Keyword(s):

Nervous System ◽

Transcriptional Regulation ◽

Copy Number ◽

System Development ◽

Copy Number Variant ◽

Brain Regions ◽

Autism Spectrum ◽

Nervous System Development ◽

Biological Pathways ◽

Non Coding Rnas

ABSTRACTBackgroundGenetic and environmental factors, alone or in combination, contribute to the pathogenesis of autism spectrum disorder (ASD). Although many protein-coding genes have now been identified as disease risk genes for ASD, a detailed illustration of long non-coding RNAs (lncRNAs) associated with ASD remains elusive. In this study, our aim was to identify ASD-related lncRNAs and explore their functions and associated biological pathways in autism.MethodsASD-related lncRNAs were identified based on genomic variant data of individuals with ASD from a twin study, and further validated using an independent copy number variant (CNV) dataset. The functions and associated biological pathways of ASD-related lncRNAs were explored by enrichment analysis of three different types of functional neighbor genes (i.e. genomic neighbors, competing endogenous RNA (ceRNA) neighbors and gene co-expression neighbors in the cortex). The differential functions of ASD-related lncRNAs in distinct brain regions were demonstrated by using gene co-expression network analysis based on tissue-specific gene expression profiles. Moreover, a functional network analysis were conducted for highly reliable functional neighbor genes of ASD-related lncRNAs. Finally, several potential drugs were predicted based on the enrichment of drug-induced pathway sets in ASD-altered biological pathway list.ResultsIn total, 532 ASD-related lncRNAs were identified, and 86.7% of these ASD-related lncRNAs were further validated by a copy number variant (CNV) dataset. Most of functional neighbor genes of ASD-related lncRNAs were enriched in several functions and biological pathways, including nervous system development, inflammatory response and transcriptional regulation. As a set, ASD-related lncRNAs were mainly associated with nervous system development and dopaminergic synapse in the cortex, but associated with transcriptional regulation in the cerebellum. Moreover, all highly reliable functional neighbor genes were connected in a single functional network. Finally, several potential drugs were predicted and partly supported by the previous reports.ConclusionsWe concluded that ASD-related lncRNAs participate in the pathogenesis of ASD through various known biological pathways, which may be differential in distinct brain regions. And detailed investigation of ASD-related lncRNAs also provided clues for developing potential ASD diagnosis biomarker and therapy.

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Faculty Opinions recommendation of Genome-wide activity-dependent MeCP2 phosphorylation regulates nervous system development and function.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.13371088.14741249 ◽

2011 ◽

Author(s):

David Sweatt ◽

Faraz Sultan

Keyword(s):

Nervous System ◽

System Development ◽

Nervous System Development ◽

Genome Wide ◽

And Function ◽

Activity Dependent

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Antenatal Glucocorticoids Supplementation and Central Nervous System Development

Current Drug Metabolism ◽

10.2174/1389200211314020002 ◽

2013 ◽

Vol 14 (2) ◽

pp. 160-166

Author(s):

Diego Gazzolo ◽

Laura D. Serpero ◽

Alessandro Frigiola ◽

Raul Abella ◽

Alessandro Giamberti ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

System Development ◽

Nervous System Development ◽

Central Nervous System Development

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Incorporation of 5-Bromo-2′-deoxyuridine into DNA and Proliferative Behavior of Cerebellar Neuroblasts: All That Glitters Is Not Gold

Cells ◽

10.3390/cells10061453 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1453

Author(s):

Joaquín Martí-Clúa

Keyword(s):

Central Nervous System ◽

Nervous System ◽

System Development ◽

Nervous System Development ◽

Current Data ◽

Cellular Mechanisms ◽

Dividing Cells ◽

The Central Nervous System ◽

Repeated Doses ◽

Pyrimidine Analog

The synthetic halogenated pyrimidine analog, 5-bromo-2′-deoxyuridine (BrdU), is a marker of DNA synthesis. This exogenous nucleoside has generated important insights into the cellular mechanisms of the central nervous system development in a variety of animals including insects, birds, and mammals. Despite this, the detrimental effects of the incorporation of BrdU into DNA on proliferation and viability of different types of cells has been frequently neglected. This review will summarize and present the effects of a pulse of BrdU, at doses ranging from 25 to 300 µg/g, or repeated injections. The latter, following the method of the progressively delayed labeling comprehensive procedure. The prenatal and perinatal development of the cerebellum are studied. These current data have implications for the interpretation of the results obtained by this marker as an index of the generation, migration, and settled pattern of neurons in the developing central nervous system. Caution should be exercised when interpreting the results obtained using BrdU. This is particularly important when high or repeated doses of this agent are injected. I hope that this review sheds light on the effects of this toxic maker. It may be used as a reference for toxicologists and neurobiologists given the broad use of 5-bromo-2′-deoxyuridine to label dividing cells.

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