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Silencing of long non-coding RNA CRNDE promotes autophagy and alleviates neonatal hypoxic-ischemic brain damage in rats

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Abstract

Hypoxic-ischemic (HI) brain damage (HIBD) leads to high neonatal mortality and severe neurologic morbidity. Autophagy is involved in the pathogenesis of HIBD. This study aims to investigate the effect of long non-coding RNA colorectal neoplasia differentially expressed (CRNDE) on HIBD and to validate whether autophagy is involved in this process. A HIBD model in rat pups and a HI model in rat primary cerebrocortical neurons were established. Autophagy was evaluated by western blot. The HIBD in rats was evaluated by hematoxylin and eosin staining, TUNEL staining, triphenyl tetrazolium chloride staining, and morris water maze test. The HI injury in vitro was evaluated by determining cell viability and apoptosis. The results showed that CRNDE expression was time-dependently increased in the brain after HIBD. Administration with CRNDE shRNA-expressing lentiviruses alleviated pathological injury and apoptosis in rat hippocampus, decreased infarct volume, and improved behavior performance of rats subjected to HIBD. Furthermore, CRNDE silencing promoted cell viability and inhibited cell apoptosis in neurons exposed to HI. Moreover, CRNDE silencing promoted autophagy and the autophagy inhibitor 3-methyladenine counteracted the neuroprotective effect of CRNDE silencing on HI-induced neuronal injury both in vivo and in vitro. Collectively, CRNDE silencing alleviates HIBD, at least partially, through promoting autophagy.

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Authors and Affiliations

  1. Department of Neonatology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, China

    Chun-Hua Fu, Sai Chen, Cai-Xia Yan, Bing-Hong Zhang & Cheng-Zhi Fang

  2. Department of Pediatric, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, China

    Fang-Fang Lai

  3. Department of Psychiatry, Renmin Hospital of Wuhan University, No.99 Zhangzhidong Road, Wuchang District, Wuhan, 430060, Hubei, China

    Gao-Hua Wang

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  1. Chun-Hua Fu
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Fu, CH., Lai, FF., Chen, S. et al. Silencing of long non-coding RNA CRNDE promotes autophagy and alleviates neonatal hypoxic-ischemic brain damage in rats. Mol Cell Biochem 472, 1–8 (2020). https://doi.org/10.1007/s11010-020-03754-2

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  • DOI: https://doi.org/10.1007/s11010-020-03754-2

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