Details der Publikation - Suppression of Microglial ERO1a Alleviates Inflammation and Enhances the Efficacy of Rehabilitative Training After Ischemic Stroke

Suppression of Microglial ERO1a Alleviates Inflammation and Enhances the Efficacy of Rehabilitative Training After Ischemic Stroke

Abstract Microglia mediated inflammation plays a crucial role in cellular events and functional recovery post ischemic stroke. In the current study, we profiled the proteome changes of microglia treated with oxygen and glucose deprivation (OGD). Bioinformatics analysis identified that differentially expressed proteins (DEPs) were enriched in pathways associated with oxidate phosphorylation and mitochondrial respiratory chain at both 6h and 24h post OGD. We next focused on one validated target named endoplasmic reticulum oxidoreductase 1 alpha (ERO1a) to study its role in stroke pathophysiology. We showed that over-expression of microglial ERO1a exacerbated inflammation, cell apoptosis and behavioral outcomes post middle cerebral artery occlusion (MCAO). In contrast, suppression of microglial ERO1a significantly reduced activation of both microglia and astrocyte, along with cell apoptosis. Furthermore, knocking down microglial ERO1a improved the efficacy of rehabilitative training and enhanced the mTOR activity in spared corticospinal neurons. Our study provided novel insights into the identification of therapeutic targets and the design of rehabilitative protocols to treat ischemic stroke and other traumatic CNS injuries..

Medienart:	E-Artikel

Erscheinungsjahr:	2023
Erschienen:	2023

Enthalten in:	Zur Gesamtaufnahme - volume:60
Enthalten in:	Molecular neurobiology - 60(2023), 8 vom: 27. Apr., Seite 4429-4441

Sprache:	Englisch

Beteiligte Personen:	Ren, Jing [VerfasserIn] Lv, Yuan [VerfasserIn] Tian, Qiuyan [VerfasserIn] Sun, Li [VerfasserIn] Miao, Po [VerfasserIn] Yang, Xiaofeng [VerfasserIn] Xu, Li-Xiao [VerfasserIn] Feng, Chen-Xi [VerfasserIn] Li, Mei [VerfasserIn] Gu, Qin [VerfasserIn] Feng, Xing [VerfasserIn] Ding, Xin [VerfasserIn]

Links:	Volltext [lizenzpflichtig]

BKL:	44.90$jNeurologie
Themen:	Corticospinal neurons ERO1a Functional recovery Ischemic stroke MTOR Microglia Rehabilitative training

Anmerkungen:	© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

doi:	10.1007/s12035-023-03333-8

funding:
Förderinstitution / Projekttitel:

PPN (Katalog-ID):	OLC2144143641

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520			\|a Abstract Microglia mediated inflammation plays a crucial role in cellular events and functional recovery post ischemic stroke. In the current study, we profiled the proteome changes of microglia treated with oxygen and glucose deprivation (OGD). Bioinformatics analysis identified that differentially expressed proteins (DEPs) were enriched in pathways associated with oxidate phosphorylation and mitochondrial respiratory chain at both 6h and 24h post OGD. We next focused on one validated target named endoplasmic reticulum oxidoreductase 1 alpha (ERO1a) to study its role in stroke pathophysiology. We showed that over-expression of microglial ERO1a exacerbated inflammation, cell apoptosis and behavioral outcomes post middle cerebral artery occlusion (MCAO). In contrast, suppression of microglial ERO1a significantly reduced activation of both microglia and astrocyte, along with cell apoptosis. Furthermore, knocking down microglial ERO1a improved the efficacy of rehabilitative training and enhanced the mTOR activity in spared corticospinal neurons. Our study provided novel insights into the identification of therapeutic targets and the design of rehabilitative protocols to treat ischemic stroke and other traumatic CNS injuries.
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650		4	\|a Corticospinal neurons
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650		4	\|a mTOR
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Suppression of Microglial ERO1a Alleviates Inflammation and Enhances the Efficacy of Rehabilitative Training After Ischemic Stroke

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