Variability in Cerebrospinal Fluid MicroRNAs Through Life
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ORIGINAL ARTICLE
Variability in Cerebrospinal Fluid MicroRNAs Through Life Endika Prieto-Fernández 1 & Elixabet Lopez-Lopez 1,2 & Idoia Martin-Guerrero 1,2 & Laura Bárcena 3 & Monika Gonzalez-Lopez 3 & Ana María Aransay 3,4 & Juan José Lozano 5 & Javier Benito 6,7 & Juan Manuel Falcón-Pérez 4,8,9 & Africa Garcia-Orad 1,2 Received: 16 May 2020 / Accepted: 1 July 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract The development of the human brain starts in the first weeks of embryo differentiation. However, there are many relevant neurodevelopmental processes that take place after birth and during lifespan. Such a fine and changing scenario requires the coordinated expression of thousands of genes to achieve the proper specialization and interconnectivity. In this context, microRNAs (miRNAs), which can modulate mRNA stability and translation, are gaining recognition for their involvement in both brain development and neurodevelopmental disorders. Therefore, cerebrospinal fluid (CSF) miRNAs should be perfectly differentiated in relevant age periods. In this study, we aimed to highlight the biological variability of miRNA expression in the CSF throughout life, which is also crucial for biomarker discovery in CNS pathologies, especially in children, where they are desperately needed. We analyzed the CSF microRNAome of 14 healthy children (aged 0–7.4 years) by smallRNA-Seq and compared it with previously published data in adults (N = 7) and elders (N = 11). miR-423-5p and miR-22-3p were overexpressed in the < 1 and > 3 years groups, respectively. Additionally, we detected 18 miRNAs that reached their highest peak of expression at different time-points during the lifespan and sets of miRNAs that were exclusively expressed in a specific age group. On the contrary, miR-191-5p showed stable expression in CSF from the first year of life. Our results remark the complex differential miRNA expression profile that can be observed through life, which underlines the need for including appropriate age-matched controls when the expression of CSF miRNAs is analyzed in different pathological contexts.
Keywords Cerebrospinal fluid . MicroRNAs . Children . Biomarkers . Biological variability Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12035-020-02011-3) contains supplementary material, which is available to authorized users. * Endika Prieto-Fernández [email protected] * Elixabet Lopez-Lopez [email protected] * Idoia Martin-Guerrero [email protected] 1
Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Medicine and Nursing, University of The Basque Country (UPV/EHU), 48940 Leioa, Bizkaia, Spain
2
BioCruces Bizkaia Health Research Institute, 48903 Barakaldo, Bizkaia, Spain
3
Genome Analysis Platform, CIC bioGUNE, 48160 Derio, Bizkaia, Spain
4
Centro de Investigación Biomédica en Red de enfermedades hepáticas y digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain
5
Bioinformatic Platf
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