Shen Chan, Guo Yanghongyun, Zheng Jun, Wang Jiayu, Zhang Liangcheng
Department of Anesthesiology, Fujian Medical University Union Hospital, No. 29, Xinquan Road, Gulou District, Fuzhou, Fujian, 350001, P. R. China.
Department of Anesthesiology, Maternal and Child Health Hospital of Hubei Province, Wuhan, P. R. China.
Neurochem Res. 2025 May 30;50(3):178. doi: 10.1007/s11064-025-04420-z.
Sevoflurane is an inhalation anesthetic in pediatric anesthesia which may cause cognitive dysfunction. Our study explores the mechanisms of fat mass and obesity-associated protein (FTO) in sevoflurane-induced cognitive impairment in neonatal rats. A neonatal rat model was established by 3% sevoflurane exposure. After FTO or miR-188-5p overexpression in rats, the motor and cognitive function and hippocampal tissue were tested. A cell model was established by 3% sevoflurane exposure in hippocampal neuronal cells. After FTO overexpression, cell viability, apoptosis, and lactate dehydrogenase levels were detected. The enrichment of m6A on the pri-miR-188 was analyzed. The binding of miR-188-5p to the SRY-box transcription factor 4 (SOX4) 3'UTR sequence was detected. Sevoflurane exposure triggered cognitive impairment in neonatal rats and decreased FTO expression in hippocampus. FTO upregulation reduced cognitive impairment in neonatal rats and hippocampal neuronal cell damage in vitro. In hippocampus and cell models, FTO inhibited miR-188-5p expression by removing m6A modification on pri-miR-188. miR-188-5p inhibited SOX4 expression. miR-188-5p overexpression or SOX4 inhibition partially reversed the protective effects of FTO overexpression on hippocampal neuronal cell damage. Overexpression of miR-188-5p partially reversed the alleviative effects of FTO overexpression on cognitive impairment. In conclusion, FTO attenuates cognitive impairment in neonatal rats through the miR-188-5p/SOX4 axis via m6A modification.
七氟醚是一种用于小儿麻醉的吸入性麻醉剂，可能导致认知功能障碍。我们的研究探讨了脂肪量和肥胖相关蛋白（FTO）在七氟醚诱导新生大鼠认知损伤中的作用机制。通过暴露于3%七氟醚建立新生大鼠模型。在大鼠中过表达FTO或miR-188-5p后，检测其运动和认知功能以及海马组织。通过在海马神经元细胞中暴露于3%七氟醚建立细胞模型。过表达FTO后，检测细胞活力、凋亡和乳酸脱氢酶水平。分析了初级微小RNA-188（pri-miR-188）上N6-甲基腺苷（m6A）的富集情况。检测了miR-188-5p与SRY盒转录因子4（SOX4）3'非翻译区序列的结合情况。七氟醚暴露引发新生大鼠认知损伤，并降低海马中FTO的表达。FTO上调可减轻新生大鼠的认知损伤以及体外海马神经元细胞损伤。在海马和细胞模型中，FTO通过去除pri-miR-188上的m6A修饰来抑制miR-188-5p的表达。miR-188-5p抑制SOX4的表达。miR-188-5p过表达或SOX4抑制可部分逆转FTO过表达对海马神经元细胞损伤的保护作用。miR-188-5p过表达可部分逆转FTO过表达对认知损伤的缓解作用。综上所述，FTO通过m6A修饰经由miR-188-5p/SOX4轴减轻新生大鼠的认知损伤。
