lncRNA Xist regulates sevoflurane-induced social and emotional impairment by modulating miR-98-5p/EDEM1 signaling axis in neonatal mice

Abstract

Long non-coding RNA (lncRNA) X-inactive specific transcript (Xist) is involved in apoptosis and inflammatory injury. This study aimed to assess the role of lncRNA Xist in sevoflurane-induced social and emotional impairment and neuronal apoptosis in neonatal mice and hippocampal neuronal cells. The performance in social and emotional tests and the expression levels of lncRNA Xist and microRNA (miR)-98-5p after sevoflurane exposure were measured. Moreover, the effects of suppression of lncRNA Xist on neuronal apoptosis and endoplasmic reticulum (ER) stress were determined. Subsequently, the association among lncRNA Xist, miR-98-5p, and ER degradation-enhancing α-mannosidase-like 1 protein (EDEM1) was explored. Our results showed that lncRNA Xist increased, miR-98-5p decreased, and social and emotional impairment appeared after sevoflurane exposure. Furthermore, suppression of lncRNA Xist improved sevoflurane-induced social and emotional impairment and reduced sevoflurane-induced neuronal apoptosis and ER stress in vivo and in vitro . Moreover, lncRNA Xist negatively regulated miR-98-5p expression, and it contributed to sevoflurane-induced neuronal apoptosis and ER stress by sponging miR-98-5p. Additionally, EDEM1 was identified as a target of miR-98-5p. Our findings revealed that the knockdown of lncRNA Xist ameliorates sevoflurane-induced social and emotional impairment through inhibiting neuronal apoptosis and ER stress by targeting the miR-98-5p/EDEM1 axis.

The effect of sevoflurane exposure on cell‐type‐specific changes in the prefrontal cortex in young mice

“…The snRNA‐seq strip plot highlighted a large number of special cell‐type genes highly responsive to sevoflurane in the PFC, including several down‐regulated gene expressions ( Itm2b in the glutamatergic neurons, Eif2s3y in the GABAergic neurons, Apoe in the astrocytes, and Ptgds in the oligodendrocytes) and up‐regulated expression of Snhg11 in the microglia, which may represent potential molecular targets for sevoflurane neurotoxicity (Figure 3b). Interestingly, Xist was over‐expressed in almost all cell types, which may lead to sevoflurane‐induced social and emotional impairment (Xu et al., 2021).…”

Integrated ribosome and proteome analyses reveal insights into sevoflurane-induced long-term social behavior and cognitive dysfunctions through ADNP inhibition in neonatal mice

“…Sevoflurane (Sev) is one of the most commonly used general anesthetics in pediatric anesthesia due to its advantages of rapid induction, low respiratory irritation, and rapid recovery ( Patel & Goa, 1996 ). Various animal studies have confirmed that repeated exposure to general anesthetics during development can result in long-term cognitive impairment, fine motor injury, and social impairment in mice ( Tang et al, 2021 ; Wu et al, 2020 ; Xu et al, 2021 ; Zhang et al, 2022b ; Zhang et al, 2023 ) and non-human primates ( Neudecker et al, 2021 ). However, many questions regarding the long-term effects of general anesthesia on brain development remain unanswered.…”

Effects of lncRNA HOXA11-AS on Sevoflurane-Induced Neuronal Apoptosis and Inflammatory Responses by Regulating miR-98-5p/EphA4

“…Sun et al [ 10 ] showed that miR-98-5p could ameliorate neuronal damage induced by oxygen glucose deprivation/reoxygenation (OGD/R). Upregulation of miR-98-5p alleviated sevoflurane-induced social and emotional disorders in neonatal mice [ 12 ]. EphA4 receptors regulate neurogenesis and border formation in the developing brain [ 13 ], and the absence of EphA4 improves neuroinflammation and tissue damage induced by traumatic brain injury [ 14 ].…”