Abstract
Postoperative cognitive dysfunction in elderly patients has been related to neurodegenerative disorders and mortality. Sevoflurane anesthesia has been implicated in both postoperative cognitive dysfunction and neurotoxicity. Given the advantages of using inhaled anesthetics like sevoflurane, it is important to understand how their usage results in neurotoxicity and subsequently devise ways to circumvent or attenuate the anesthetic-mediated induction in neurotoxicity. Long noncoding RNAs (LncRNAs) are a group of > 200 bp long RNAs and show specific spatiotemporal expression profiles. Several recent reports suggest that lncRNAs are involved in responses of the central nervous system (CNS) following acute injuries. However, their role in sevoflurane anesthesia-mediated cognitive dysfunction has not been studied. RNA immunoprecipitation (RIP) combined with qRT-PCR detection of six different lncRNAs showed that the HOTAIR lncRNAs were significantly more bound to both Sin3A and coREST, both corepressors of the RE-1 silencing transcription factor, within rat hippocampus following sevoflurane anesthesia compared with sham. Sevoflurane inhalation resulted in significant inhibition of brain-derived neurotrophic factor (BDNF) and cognitive impairment. Treatment with a combination of siRNAs targeting HOTAIR rescued BDNF expression and improved cognitive responses. Taken together, our results suggest that sevoflurane-mediated brain function impairment is at least in part mediated by the HOTAIR lncRNA.
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Wang, Jy., Feng, Y., Fu, Yh. et al. Effect of Sevoflurane Anesthesia on Brain Is Mediated by lncRNA HOTAIR. J Mol Neurosci 64, 346–351 (2018). https://doi.org/10.1007/s12031-018-1029-y
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DOI: https://doi.org/10.1007/s12031-018-1029-y