LncRNA MALAT1 is involved in sevoflurane‐induced neurotoxicity in developing rats

Abstract

Objective The purpose of this study is to uncover the effects of long chain noncoding RNA (lncRNA) metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) on sevoflurane‐induced neurotoxicity in developing rats. Methods Sevoflurane neurotoxicity model was established by sevoflurane treatment in 7‐day‐old Sprague‐Dawley rats. The rats were treated with Sevo or MALAT1 small interfering RNA to detect the MALAT1 expression, pathological change, ultrastructure, neuronal apoptosis, expression of apoptosis‐related proteins, expression of neurotrophic factors BDNF and NGF, spatial learning and memory function change, as well as neuron cell density of hippocampal tissues. Results MALAT1 was highly expressed in hippocampus tissues of rats. Downregulation of MALAT1 alleviated the pathological change, improved the ultrastructure, inhibited apoptosis of neuronal cells, declined caspase 3 and Bax while elevated Bcl‐2, BDNF and NGF, improved capability of spatial learning and memory, and increased density of hippocampal neurons in hippocampal tissues of sevoflurane‐induced rats. Conclusion Suppression of MALAT1 can reduce the apoptosis of hippocampal neurons induced by sevoflurane anesthesia, improve the capability of spatial learning, and memory function and alleviate the loss of hippocampal nerve cells in developing rats. To a certain extent, it plays the role of protecting brain nerve cells.

Long non-coding RNA Peg13 attenuates the sevoflurane toxicity against neural stem cells by sponging microRNA-128-3p to preserve Sox13 expression

“…Hence, our findings may provide new insights into the pathogenesis of sevoflurane-related neurotoxicity. Our findings, together with facts that sevoflurane exposure significantly up-regulated lncRNA Gadd45a expression and lncRNA HOTAIR in rat hippocampus [25,36], but down-regulated LncRNA Malat1 expression in infant rats [37], suggest that different lncRNAs may have varying functions and form a network in regulating the sevoflurane-related neurotoxicity against NSCs. This regulatory network will determine the self-renewal and differentiation of NSCs.…”

Sevoflurane inhibits progression of glioma via regulating the HMMR antisense RNA 1/microRNA-7/cyclin dependent kinase 4 axis

“…LncRNAs are involved in the pathology of brain tumors, including glioma [ 38 ]. Moreover, lncRNA-mediated networks are responsible for understanding the activity of Sev [ 10 ], such as lncRNA metastasis-associated lung adenocarcinoma transcript 1 and small nucleolar RNA host gene 1 [ 39 , 40 ]. Here we were the first to confirm HMMR-AS1 was decreased via Sev in glioma cells.…”

The Role of Epigenetic Modifications in Neurotoxicity Induced by Neonatal General Anesthesia

“…The lncRNAs are another class of ncRNAs, recent studies have identified many paradigms that illustrate how lncRNAs function, including targeting proteins to specific genomic location to affect transcription patterns, modulating the activity of protein-binding partners and serving as precursors for small RNAs ( Wilusz et al, 2009 ). A recent study in 2018 uncovered the effects of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) on sevoflurane-induced neurotoxicity in developing rats ( Hu et al, 2019 ). It demonstrated that rats anesthetized with sevoflurane show the high expression of MALAT1, the downregulation of BDNF and NGF mRNA and protein levels, the increase of neuron apoptosis and pathological structural changes in hippocampus and the impairment of spatial learning and memory ability.…”