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Open AccessArticle

Age-Associated mRNA and miRNA Expression Changes in the Blood-Brain Barrier

1
Sheffield Institute for Translational Neuroscience, 385a Glossop Road, University of Sheffield, Sheffield S10 2HQ, UK
2
School of Life Science, Health and Chemical Sciences, Faculty of Science, Technology Engineering and Mathematics, The Open University, Walton Hall, Milton Keynes MK7 6AA, UK
*
Author to whom correspondence should be addressed.
Joint first authors.
Joint senior authors.
Int. J. Mol. Sci. 2019, 20(12), 3097; https://doi.org/10.3390/ijms20123097
Received: 6 June 2019 / Revised: 21 June 2019 / Accepted: 22 June 2019 / Published: 25 June 2019
Functional and structural age-associated changes in the blood-brain barrier (BBB) may affect the neurovascular unit and contribute to the onset and progression of age-associated neurodegenerative pathologies, including Alzheimer’s disease. The current study interrogated the RNA profile of the BBB in an ageing human autopsy brain cohort and an ageing mouse model using combined laser capture microdissection and expression profiling. Only 12 overlapping genes were altered in the same direction in the BBB of both ageing human and mouse cohorts. These included genes with roles in regulating vascular tone, tight junction protein expression and cell adhesion, all processes prone to dysregulation with advancing age. Integrated mRNA and miRNA network and pathway enrichment analysis of the datasets identified 15 overlapping miRNAs that showed altered expression. In addition to targeting genes related to DNA binding and/or autophagy, many of the miRNAs identified play a role in age-relevant processes, including BBB dysfunction and regulating the neuroinflammatory response. Future studies have the potential to develop targeted therapeutic approaches against these candidates to prevent vascular dysfunction in the ageing brain. View Full-Text
Keywords: ageing; blood brain barrier; gene expression; miRNA ageing; blood brain barrier; gene expression; miRNA
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Goodall, E.F.; Leach, V.; Wang, C.; Cooper-Knock, J.; Heath, P.R.; Baker, D.; Drew, D.R.; Saffrey, M.J.; Simpson, J.E.; Romero, I.A.; Wharton, S.B. Age-Associated mRNA and miRNA Expression Changes in the Blood-Brain Barrier. Int. J. Mol. Sci. 2019, 20, 3097.

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