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An Examination of the Role of MicroR...

Laliberte, Alex Michael.

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An Examination of the Role of MicroRNA-21 in the Pathobiology of Degenerative Cervical Myelopathy Using Human and Animal Data.

Record Type:	Electronic resources : Monograph/item
Title/Author:	An Examination of the Role of MicroRNA-21 in the Pathobiology of Degenerative Cervical Myelopathy Using Human and Animal Data./
Author:	Laliberte, Alex Michael.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2018,
Description:	221 p.
Notes:	Source: Dissertations Abstracts International, Volume: 80-06, Section: B.
Contained By:	Dissertations Abstracts International80-06B.
Subject:	Molecular biology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10831454
ISBN:	9780438682474

An Examination of the Role of MicroRNA-21 in the Pathobiology of Degenerative Cervical Myelopathy Using Human and Animal Data.
Laliberte, Alex Michael.

An Examination of the Role of MicroRNA-21 in the Pathobiology of Degenerative Cervical Myelopathy Using Human and Animal Data. - Ann Arbor : ProQuest Dissertations & Theses, 2018 - 221 p.

Source: Dissertations Abstracts International, Volume: 80-06, Section: B.

Thesis (Ph.D.)--University of Toronto (Canada), 2018.

This item must not be sold to any third party vendors.

MicroRNA-21 (miR-21) is upregulated in multiple models of traumatic and neuroinflammatory CNS injury. Here, we sought to evaluate the role of miR-21 in the most common form of adult spinal cord dysfunction, degenerative cervical myelopathy (DCM). Using a mouse model of DCM where the spinal cord is progressively compressed over multiple weeks, we found elevated expression of miR-21 in both spinal cord and plasma at 6 weeks and 12 weeks after onset. Deletion of miR-21 in a null mutant mouse strain significantly preserved locomotor function on the rotarod and forced swim tests, but at the cost of increased neuropathic pain. Preservation of motor function was attributed to reduced inflammation, denoted by the approximately 50% reduction in stereological counts of Iba1-positive activated microglia in miR-21 knockout spinal cord sections. In vitro experiments using primary microglia found that miR-21 is induced under pro- or anti-inflammatory conditions, but that miR-21 deletion did not affect the cells natural reaction to these stimuli. Target prediction algorithms identified the IL-6/STAT3 pathway as a potential downstream target of miR-21, and subsequent in vitro testing found that components of the IL-6 receptor complex, IL-6ra, and IL-6st were significantly higher in miR-21 knockout microglia. Finally, to determine whether miR-21 and other microRNAs related to human DCM could be used as biomarkers, we examined plasma microRNA expression in a human DCM cohort. Expression of miR-21 and other microRNAs were found to be correlated to current patient symptoms. In the surgical cohort, baseline levels of miR-132-3p and miR-34a were found to predict surgical outcome, while miR-21 approached a statistically significant correlation with post-operative lower motor function (p=0.05). In aggregate, we find that miR-21 may have a pro-inflammatory role in the DCM microglial response, and that miR-21 expression may be related to the manifestation of motor deficits.

ISBN: 9780438682474Subjects--Topical Terms:

517296
Molecular biology.

An Examination of the Role of MicroRNA-21 in the Pathobiology of Degenerative Cervical Myelopathy Using Human and Animal Data.
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520 $a MicroRNA-21 (miR-21) is upregulated in multiple models of traumatic and neuroinflammatory CNS injury. Here, we sought to evaluate the role of miR-21 in the most common form of adult spinal cord dysfunction, degenerative cervical myelopathy (DCM). Using a mouse model of DCM where the spinal cord is progressively compressed over multiple weeks, we found elevated expression of miR-21 in both spinal cord and plasma at 6 weeks and 12 weeks after onset. Deletion of miR-21 in a null mutant mouse strain significantly preserved locomotor function on the rotarod and forced swim tests, but at the cost of increased neuropathic pain. Preservation of motor function was attributed to reduced inflammation, denoted by the approximately 50% reduction in stereological counts of Iba1-positive activated microglia in miR-21 knockout spinal cord sections. In vitro experiments using primary microglia found that miR-21 is induced under pro- or anti-inflammatory conditions, but that miR-21 deletion did not affect the cells natural reaction to these stimuli. Target prediction algorithms identified the IL-6/STAT3 pathway as a potential downstream target of miR-21, and subsequent in vitro testing found that components of the IL-6 receptor complex, IL-6ra, and IL-6st were significantly higher in miR-21 knockout microglia. Finally, to determine whether miR-21 and other microRNAs related to human DCM could be used as biomarkers, we examined plasma microRNA expression in a human DCM cohort. Expression of miR-21 and other microRNAs were found to be correlated to current patient symptoms. In the surgical cohort, baseline levels of miR-132-3p and miR-34a were found to predict surgical outcome, while miR-21 approached a statistically significant correlation with post-operative lower motor function (p=0.05). In aggregate, we find that miR-21 may have a pro-inflammatory role in the DCM microglial response, and that miR-21 expression may be related to the manifestation of motor deficits.
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