Open AccessSilencing of long non‑coding antisense RNA brain‑derived neurotrophic factor attenuates hypoxia/ischemia‑induced neonatal brain injury
Author(s) -
Lixing Qiao,
Ran Zhao,
Mingfu Wu,
Lihua Zhu,
Zhengkun Xia
Publication year - 2020
Publication title -
international journal of molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.048
H-Index - 90
eISSN - 1791-244X
pISSN - 1107-3756
DOI - 10.3892/ijmm.2020.4625
Subject(s) - neurotrophic factors , gene silencing , brain derived neurotrophic factor , tropomyosin receptor kinase b , biology , brain damage , hippocampal formation , glial cell line derived neurotrophic factor , neuroscience , receptor , gene , biochemistry
Hypoxic/ischemic (HI) brain damage (HIBD) is a major cause of acute neonatal brain injury, leading to high mortality and serious neurological deficits. The antisense RNA of brain‑derived neurotrophic factor (BDNF‑AS) is transcribed from the opposite strand of the BDNF gene. The aim of the present study was to investigate the role of BDNF‑AS in HI‑induced neuronal cell injury in vivo and in vitro. Reverse transcription‑quantitative PCR (RT‑qPCR) assays indicated that BDNF‑AS expression was significantly upregulated in HI‑injured neonatal brains and hippocampal neurons. However, BDNF expression was downregulated in HI‑injured neonatal brains and hippocampal neurons. Cell Counting Kit‑8 assays, Hoechst staining, calcein‑AM/PI staining, immunostaining, water maze tests and rotarod tests demonstrated that BDNF‑AS silencing protected against hypoxia‑induced primary hippocampal neuron injury in vitro and HI‑induced brain injury in vivo. Mechanistically, RT‑qPCR assays and western blotting indicated that BDNF‑AS silencing led to increased expression of BDNF and activated the BDNF‑mediated signaling pathway, as demonstrated by increased expression levels of BDNF, phosphorylated‑Akt and phosphorylated‑tropomyosin receptor kinase B. Collectively, the present study provides important insights into the pathogenesis of HIBD, and it was indicated that BDNF‑AS silencing may be a promising approach for the treatment of neonatal HIBD.