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MicroRNA expression within neuronal-derived small extracellular vesicles in frontotemporal degeneration

MicroRNAs (miRNAs) are small non-coding RNA that are powerful regulators of gene expression and can affect the expression of hundreds of genes. miRNAs can be packed in small extracellular vesicles (SEV) and released into the extracellular space by neurons and microglia to act locally as well as pass...

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Autores principales: Pounders, Jonathan, Hill, Emily J., Hooper, Destiny, Zhang, Xiang, Biesiada, Jacek, Kuhnell, Damaris, Greenland, Hannah L., Esfandiari, Leyla, Timmerman, Emerlee, Foster, Forrest, Wang, Chenran, Walsh, Kyle B., Shatz, Rhonna, Woo, Daniel, Medvedovic, Mario, Langevin, Scott, Sawyer, Russell P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9542922/
https://www.ncbi.nlm.nih.gov/pubmed/36221381
http://dx.doi.org/10.1097/MD.0000000000030854
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author Pounders, Jonathan
Hill, Emily J.
Hooper, Destiny
Zhang, Xiang
Biesiada, Jacek
Kuhnell, Damaris
Greenland, Hannah L.
Esfandiari, Leyla
Timmerman, Emerlee
Foster, Forrest
Wang, Chenran
Walsh, Kyle B.
Shatz, Rhonna
Woo, Daniel
Medvedovic, Mario
Langevin, Scott
Sawyer, Russell P.
author_facet Pounders, Jonathan
Hill, Emily J.
Hooper, Destiny
Zhang, Xiang
Biesiada, Jacek
Kuhnell, Damaris
Greenland, Hannah L.
Esfandiari, Leyla
Timmerman, Emerlee
Foster, Forrest
Wang, Chenran
Walsh, Kyle B.
Shatz, Rhonna
Woo, Daniel
Medvedovic, Mario
Langevin, Scott
Sawyer, Russell P.
author_sort Pounders, Jonathan
collection PubMed
description MicroRNAs (miRNAs) are small non-coding RNA that are powerful regulators of gene expression and can affect the expression of hundreds of genes. miRNAs can be packed in small extracellular vesicles (SEV) and released into the extracellular space by neurons and microglia to act locally as well as pass through the blood-brain barrier and act systemically. We sought to understand the differences in neuronal SEV miRNA expression between frontotemporal dementia (FTD), Alzheimer’s disease (AD), and healthy aging. Plasma was obtained from FTD, AD, and healthy aging participants that were matched based on age, sex, and race/ethnicity. Additionally, a subset of participants also provided paired cerebrospinal fluid samples to compare neuronal SEV miRNAs in plasma and cerebrospinal fluid. Neuronal SEV were isolated using differential ultracentrifugation and antibody conjugated Dynabeads® for the neuronal surface marker, L1CAM. RNA sequencing was performed. 12 FTD, 11 with AD, and 10 healthy aging participants were enrolled in the study. In FTD, SEV miRNA-181c was downregulated compared to healthy controls. In AD, miRNA-122 and miRNA-3591 were downregulated compared to those in healthy controls and FTD. Using an FDR <0.2, only miRNA-21-5p was found to have increased expression in the cerebrospinal fluid compared to plasma in a group of AD and FTD participants. SEV miRNA-181c is significantly downregulated in FTD compared to healthy controls and may mediate its effects through microglial-directed neuroinflammation and interaction with TAR DNA-binding protein 43 (TDP-43) based on pathway analysis. Additionally, the FOXO and Hippo pathways may be important mediators of FTD, based on pathway analysis. Lastly, because only one SEV miRNA was differentially expressed between the plasma and cerebrospinal fluid in paired samples, plasma represents an appropriate biofluid for studying neuronal SEV miRNA.
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spelling pubmed-95429222022-10-11 MicroRNA expression within neuronal-derived small extracellular vesicles in frontotemporal degeneration Pounders, Jonathan Hill, Emily J. Hooper, Destiny Zhang, Xiang Biesiada, Jacek Kuhnell, Damaris Greenland, Hannah L. Esfandiari, Leyla Timmerman, Emerlee Foster, Forrest Wang, Chenran Walsh, Kyle B. Shatz, Rhonna Woo, Daniel Medvedovic, Mario Langevin, Scott Sawyer, Russell P. Medicine (Baltimore) Research Article MicroRNAs (miRNAs) are small non-coding RNA that are powerful regulators of gene expression and can affect the expression of hundreds of genes. miRNAs can be packed in small extracellular vesicles (SEV) and released into the extracellular space by neurons and microglia to act locally as well as pass through the blood-brain barrier and act systemically. We sought to understand the differences in neuronal SEV miRNA expression between frontotemporal dementia (FTD), Alzheimer’s disease (AD), and healthy aging. Plasma was obtained from FTD, AD, and healthy aging participants that were matched based on age, sex, and race/ethnicity. Additionally, a subset of participants also provided paired cerebrospinal fluid samples to compare neuronal SEV miRNAs in plasma and cerebrospinal fluid. Neuronal SEV were isolated using differential ultracentrifugation and antibody conjugated Dynabeads® for the neuronal surface marker, L1CAM. RNA sequencing was performed. 12 FTD, 11 with AD, and 10 healthy aging participants were enrolled in the study. In FTD, SEV miRNA-181c was downregulated compared to healthy controls. In AD, miRNA-122 and miRNA-3591 were downregulated compared to those in healthy controls and FTD. Using an FDR <0.2, only miRNA-21-5p was found to have increased expression in the cerebrospinal fluid compared to plasma in a group of AD and FTD participants. SEV miRNA-181c is significantly downregulated in FTD compared to healthy controls and may mediate its effects through microglial-directed neuroinflammation and interaction with TAR DNA-binding protein 43 (TDP-43) based on pathway analysis. Additionally, the FOXO and Hippo pathways may be important mediators of FTD, based on pathway analysis. Lastly, because only one SEV miRNA was differentially expressed between the plasma and cerebrospinal fluid in paired samples, plasma represents an appropriate biofluid for studying neuronal SEV miRNA. Lippincott Williams & Wilkins 2022-10-07 /pmc/articles/PMC9542922/ /pubmed/36221381 http://dx.doi.org/10.1097/MD.0000000000030854 Text en Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY) (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Pounders, Jonathan
Hill, Emily J.
Hooper, Destiny
Zhang, Xiang
Biesiada, Jacek
Kuhnell, Damaris
Greenland, Hannah L.
Esfandiari, Leyla
Timmerman, Emerlee
Foster, Forrest
Wang, Chenran
Walsh, Kyle B.
Shatz, Rhonna
Woo, Daniel
Medvedovic, Mario
Langevin, Scott
Sawyer, Russell P.
MicroRNA expression within neuronal-derived small extracellular vesicles in frontotemporal degeneration
title MicroRNA expression within neuronal-derived small extracellular vesicles in frontotemporal degeneration
title_full MicroRNA expression within neuronal-derived small extracellular vesicles in frontotemporal degeneration
title_fullStr MicroRNA expression within neuronal-derived small extracellular vesicles in frontotemporal degeneration
title_full_unstemmed MicroRNA expression within neuronal-derived small extracellular vesicles in frontotemporal degeneration
title_short MicroRNA expression within neuronal-derived small extracellular vesicles in frontotemporal degeneration
title_sort microrna expression within neuronal-derived small extracellular vesicles in frontotemporal degeneration
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9542922/
https://www.ncbi.nlm.nih.gov/pubmed/36221381
http://dx.doi.org/10.1097/MD.0000000000030854
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