TXNIP/NLRP3 aggravates global cerebral ischemia-reperfusion injury-induced cognitive decline in mice

Chengjie Yang; Jing Mo; Qingmei Liu; Wei Li; Ye Chen; Jianguo Feng; Jing Jia; Li Liu; Yiping Bai; Jun Zhou

Heliyon (Mar 2024)

TXNIP/NLRP3 aggravates global cerebral ischemia-reperfusion injury-induced cognitive decline in mice

Chengjie Yang,
Jing Mo,
Qingmei Liu,
Wei Li,
Ye Chen,
Jianguo Feng,
Jing Jia,
Li Liu,
Yiping Bai,
Jun Zhou

Affiliations

Chengjie Yang: Department of Anesthesiology, The Affiliated Hospital, Southwest Medical University, Luzhou, China; Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, Southwest Medical University, Luzhou, Sichuan Province, China
Jing Mo: Department of Anesthesiology, The Affiliated Hospital, Southwest Medical University, Luzhou, China; Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, Southwest Medical University, Luzhou, Sichuan Province, China
Qingmei Liu: Department of Anesthesiology, The Affiliated Hospital, Southwest Medical University, Luzhou, China; Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, Southwest Medical University, Luzhou, Sichuan Province, China
Wei Li: Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, Southwest Medical University, Luzhou, Sichuan Province, China; Department of Anesthesiology, He Jiang People's Hospital, Luzhou, China
Ye Chen: Department of Traditional Chinese Medicine, The Affiliated Hospital, Southwest Medical University, Luzhou, China; Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, Southwest Medical University, Luzhou, Sichuan Province, China
Jianguo Feng: Department of Anesthesiology, The Affiliated Hospital, Southwest Medical University, Luzhou, China; Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, Southwest Medical University, Luzhou, Sichuan Province, China
Jing Jia: Department of Anesthesiology, The Affiliated Hospital, Southwest Medical University, Luzhou, China; Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, Southwest Medical University, Luzhou, Sichuan Province, China
Li Liu: Department of Anesthesiology, The Affiliated Hospital, Southwest Medical University, Luzhou, China; Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, Southwest Medical University, Luzhou, Sichuan Province, China
Yiping Bai: Department of Anesthesiology, The Affiliated Hospital, Southwest Medical University, Luzhou, China; Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, Southwest Medical University, Luzhou, Sichuan Province, China
Jun Zhou: Department of Anesthesiology, The Affiliated Hospital, Southwest Medical University, Luzhou, China; Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, Southwest Medical University, Luzhou, Sichuan Province, China; Corresponding author. Department of Anesthesiology, The Affiliated Hospital, Southwest Medical University, No.25 Taiping Street, Luzhou, Sichuan Province, 646000, China.

Journal volume & issue: Vol. 10, no. 6
p. e27423

Abstract

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Global cerebral ischemia/reperfusion (GCI/R) injury poses a risk for cognitive decline, with neuroinflammation considered pivotal in this process. This study aimed to unravel the molecular mechanisms underlying GCI/R injury and propose a potential therapeutic strategy for associated cognitive deficits. Utilizing bioinformatics analysis of a public microarray profile (GSE30655 and GSE80681) in cerebral ischemic mice, it was observed that neuroinflammation emerged as a significant gene ontology item, with an increase in the expression of thioredoxin-interacting protein (TXNIP) and NLRP3 genes. Experimental models involving bilateral occlusion of the common carotid arteries in mice revealed that GCI/R induced cognitive impairment, along with a time-dependent increase in TXNIP and NLRP3 levels. Notably, TXNIP knockdown alleviated cognitive dysfunction in mice. Furthermore, the introduction of adeno-associated virus injection with TXNIP knockdown reduced the number of activated microglia, apoptosis neurons, and levels of oxidative stress and inflammatory cytokines in the hippocampus. Collectively, these findings underscore the significance of TXNIP/NLRP3 in the hippocampus in exacerbating cognitive decline due to GCI/R injury, suggesting that TXNIP knockdown holds promise as a therapeutic strategy.

Published in Heliyon

ISSN: 2405-8440 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Science: Science (General); Social Sciences: Social sciences (General)
Website: https://www.cell.com/heliyon/home

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