DNA2 Knockout Aggravates Cerebral Ischemia/reperfusion Injury by Reducing Postsynaptic Homer1a

Overview

Journal Zool Res

Publisher Science Press

Date 2025 Jan 23

PMID 39846189

Authors

Ting Ma

Yu-Meng Li

Peng-Yu Ren

Shi-Quan Wang

Xiang-Long Liu

Wen-Bo Lv

Wu-Gang Hou

Wen-Qiang Zuo

Wei-Qiang Lin

Jian Sima

An-Qi Geng

Affiliations

Soon will be listed here.

Abstract

DNA2, a multifunctional enzyme with structure-specific nuclease, 5 -to-3 helicase, and DNA-dependent ATPase activities, plays a pivotal role in the cellular response to DNA damage. However, its involvement in cerebral ischemia/reperfusion (I/R) injury remains to be elucidated. This study investigated the involvement of DNA2 in cerebral I/R injury using conditional knockout (cKO) mice ( -Cre) subjected to middle cerebral artery occlusion (MCAO), an established model of cerebral I/R. Results demonstrated a gradual up-regulation of DNA2 expression, peaking at 72 h post-MCAO. Notably, cKO mice exhibited more pronounced brain injury, neurological deficits, and neuronal apoptosis within the penumbra following MCAO. Additionally, DNA2 expression was elevated in an oxygen-glucose deprivation/reoxygenation (OGD/R) cell culture model, and knockdown (KD) exacerbated neuronal apoptosis and oxidative stress. Transcriptome analysis of ischemic penumbra tissues via RNA sequencing revealed significant down-regulation of in cKO mice. Furthermore, experiments demonstrated that overexpression of ameliorated KD-induced neuronal apoptosis. Collectively, these findings demonstrate that deficiency exacerbates cerebral I/R injury through the down-regulation of , highlighting a novel regulatory axis in ischemic neuroprotection.

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