Inhibition of long non-coding RNA IGF2AS protects apoptosis and neuronal loss in anesthetic-damaged mouse neural stem cell derived neurons.

Chengwei Song, Chengjun Song, Kui Chen, Xiangdong Zhang

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 2017 Jan

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In vitro culture of neural stem cell-derived neurons serves as an excellent model to study anesthetic-induced neurotoxicity. In our study, we examined the functional role of long non-coding RNA, IGF2AS, in regulating ketamine-induced neurotoxicity in murine neural stem cells. Murine E18.5 brain-derived neural stem cells were cultured in vitro. During neural differentiation stage, ketamine-induced gene expression changes of IGF2 and IGF2AS were recorded by qRT-PCR. Neural stem cell culture was then infected by IGF2AS siRNA. The protective effect of IGF2AS inhibition on ketamine-induced apoptosis and neurite loss was assessed by TUNEL and neurite growth assays. BDNF and Akt, two candidates of downstream signaling pathways associated with IGF2AS inhibition, were further examined by western blot in neural stem cell culture. In neural stem cell culture, IGF2 was downregulated, but IGF2AS upregulated by in vitro treatment of ketamine in dose-dependent manner. Transfection of IGF2AS-specific siRNA effectively downregulated endogenous IGF2AS expression in neural stem cells. In addition, IGF2AS inhibition significantly alleviated ketamine-induced neuronal apoptosis and neurite loss in neural stem cell-derived neurons. Western blot study revealed that IGF2AS inhibition upregulated downstream pro-neuronal signaling pathway proteins BDNF and Akt. Inhibiting endogenous IGF2AS can protect anesthetic-induced neurotoxicity in neural stem cells, possibly through complimentary IGF2 upregulation and its associated downstream signaling pathways. Copyright © 2016. Published by Elsevier Masson SAS.

Citation

Chengwei Song, Chengjun Song, Kui Chen, Xiangdong Zhang. Inhibition of long non-coding RNA IGF2AS protects apoptosis and neuronal loss in anesthetic-damaged mouse neural stem cell derived neurons. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2017 Jan;85:218-224