Variability in Cerebrospinal Fluid MicroRNAs Through Life.

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 inter-connectivity. 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  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. Graphical abstract.