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MicroRNA miR-155 Activity in Mouse Choline Acetyltransferase-Positive Neurons Is Critical for the Rate of Early and Late Paraplegia After Transient Aortic Cross-Clamping

Aortic aneurism open repair surgery can cause spinal cord (SC) injury with 5–15% of patients developing paraparesis or paraplegia. Using a mouse model of transient aortic cross-clamping (ACC), we have previously found that the expression of proinflammatory microRNA miR-155 increases in motoneurons (...

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Autores principales: Kelani, Hesham, Nuovo, Gerard, Bratasz, Anna, Rajan, Jayanth, Efanov, Alexander A., Michaille, Jean-Jacques, Awad, Hamdy, Tili, Esmerina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8850917/
https://www.ncbi.nlm.nih.gov/pubmed/35185466
http://dx.doi.org/10.3389/fnmol.2022.788301
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author Kelani, Hesham
Nuovo, Gerard
Bratasz, Anna
Rajan, Jayanth
Efanov, Alexander A.
Michaille, Jean-Jacques
Awad, Hamdy
Tili, Esmerina
author_facet Kelani, Hesham
Nuovo, Gerard
Bratasz, Anna
Rajan, Jayanth
Efanov, Alexander A.
Michaille, Jean-Jacques
Awad, Hamdy
Tili, Esmerina
author_sort Kelani, Hesham
collection PubMed
description Aortic aneurism open repair surgery can cause spinal cord (SC) injury with 5–15% of patients developing paraparesis or paraplegia. Using a mouse model of transient aortic cross-clamping (ACC), we have previously found that the expression of proinflammatory microRNA miR-155 increases in motoneurons (MNs) and endothelial cells (ECs) of ischemic SCs, and that global miR-155 deletion decreases the percentage of paraplegia by 37.4% at 48-h post-ACC. Here, we investigated the cell-specific contribution of miR-155 in choline acetyltransferase-positive (ChAT(+)) neurons (that include all MNs of the SC) and ECs to SC injury after ACC. Mice lacking miR-155 in ChAT(+) neurons (MN-miR-155-KO mice) developed 24.6% less paraplegia than control mice at 48-h post-ACC. In contrast, mice lacking miR-155 in ECs (ECs-miR-155-KO mice) experienced the same percentage of paraplegia as control mice, despite presenting smaller central cord edema. Unexpectedly, mice overexpressing miR-155 in ChAT(+) neurons were less likely than control mice to develop early paraplegia during the first day post-ACC, however they reached the same percentage of paraplegia at 48-h. In addition, all mice overexpressing miR-155 in ECs (ECs-miR-155-KI mice) were paraplegic at 48-h post-ACC. Altogether, our results suggest that miR-155 activity in ChAT(+) neurons protects the SC against ischemic injury during the first day post-ACC before becoming deleterious during the second day, which indicates that early and late paraplegias arise from different molecular malfunctions. These results point to the need to develop specific protective therapeutics aimed at inhibiting both the early and late deleterious events after open repair surgery of aortic aneurisms.
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spelling pubmed-88509172022-02-18 MicroRNA miR-155 Activity in Mouse Choline Acetyltransferase-Positive Neurons Is Critical for the Rate of Early and Late Paraplegia After Transient Aortic Cross-Clamping Kelani, Hesham Nuovo, Gerard Bratasz, Anna Rajan, Jayanth Efanov, Alexander A. Michaille, Jean-Jacques Awad, Hamdy Tili, Esmerina Front Mol Neurosci Neuroscience Aortic aneurism open repair surgery can cause spinal cord (SC) injury with 5–15% of patients developing paraparesis or paraplegia. Using a mouse model of transient aortic cross-clamping (ACC), we have previously found that the expression of proinflammatory microRNA miR-155 increases in motoneurons (MNs) and endothelial cells (ECs) of ischemic SCs, and that global miR-155 deletion decreases the percentage of paraplegia by 37.4% at 48-h post-ACC. Here, we investigated the cell-specific contribution of miR-155 in choline acetyltransferase-positive (ChAT(+)) neurons (that include all MNs of the SC) and ECs to SC injury after ACC. Mice lacking miR-155 in ChAT(+) neurons (MN-miR-155-KO mice) developed 24.6% less paraplegia than control mice at 48-h post-ACC. In contrast, mice lacking miR-155 in ECs (ECs-miR-155-KO mice) experienced the same percentage of paraplegia as control mice, despite presenting smaller central cord edema. Unexpectedly, mice overexpressing miR-155 in ChAT(+) neurons were less likely than control mice to develop early paraplegia during the first day post-ACC, however they reached the same percentage of paraplegia at 48-h. In addition, all mice overexpressing miR-155 in ECs (ECs-miR-155-KI mice) were paraplegic at 48-h post-ACC. Altogether, our results suggest that miR-155 activity in ChAT(+) neurons protects the SC against ischemic injury during the first day post-ACC before becoming deleterious during the second day, which indicates that early and late paraplegias arise from different molecular malfunctions. These results point to the need to develop specific protective therapeutics aimed at inhibiting both the early and late deleterious events after open repair surgery of aortic aneurisms. Frontiers Media S.A. 2022-02-03 /pmc/articles/PMC8850917/ /pubmed/35185466 http://dx.doi.org/10.3389/fnmol.2022.788301 Text en Copyright © 2022 Kelani, Nuovo, Bratasz, Rajan, Efanov, Michaille, Awad and Tili. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Kelani, Hesham
Nuovo, Gerard
Bratasz, Anna
Rajan, Jayanth
Efanov, Alexander A.
Michaille, Jean-Jacques
Awad, Hamdy
Tili, Esmerina
MicroRNA miR-155 Activity in Mouse Choline Acetyltransferase-Positive Neurons Is Critical for the Rate of Early and Late Paraplegia After Transient Aortic Cross-Clamping
title MicroRNA miR-155 Activity in Mouse Choline Acetyltransferase-Positive Neurons Is Critical for the Rate of Early and Late Paraplegia After Transient Aortic Cross-Clamping
title_full MicroRNA miR-155 Activity in Mouse Choline Acetyltransferase-Positive Neurons Is Critical for the Rate of Early and Late Paraplegia After Transient Aortic Cross-Clamping
title_fullStr MicroRNA miR-155 Activity in Mouse Choline Acetyltransferase-Positive Neurons Is Critical for the Rate of Early and Late Paraplegia After Transient Aortic Cross-Clamping
title_full_unstemmed MicroRNA miR-155 Activity in Mouse Choline Acetyltransferase-Positive Neurons Is Critical for the Rate of Early and Late Paraplegia After Transient Aortic Cross-Clamping
title_short MicroRNA miR-155 Activity in Mouse Choline Acetyltransferase-Positive Neurons Is Critical for the Rate of Early and Late Paraplegia After Transient Aortic Cross-Clamping
title_sort microrna mir-155 activity in mouse choline acetyltransferase-positive neurons is critical for the rate of early and late paraplegia after transient aortic cross-clamping
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8850917/
https://www.ncbi.nlm.nih.gov/pubmed/35185466
http://dx.doi.org/10.3389/fnmol.2022.788301
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