Qin Fei, Li Fan, Zhao Wenxiao, Zhang Suqin, Shen Jiang, Yang Xinyu
Department of Neurosurgery, Tianjin Medical University General Hospital, 300052 Tianjin, China.
Department of Neurosurgery, Heji Hospital Affiliated to Changzhi Medical College, 046011 Changzhi, Shanxi, China.
Front Biosci (Landmark Ed). 2025 Apr 24;30(4):31304. doi: 10.31083/FBL31304.
Traumatic brain injury (TBI) is a disease caused by external forces that damage brain structure and function. After TBI, iron accumulation and reactive oxygen species (ROS) increase lipid peroxidation, promoting ferroptosis. Methyltransferase-like 3 () inhibits ferroptosis by modulating related signaling pathways. This study investigates the effects of on neuronal ferroptosis in TBI, offering new insights and potential therapies.
TBI mouse and neuron cell models were established and treated with overexpression. The Morris Water Maze (MWM) test evaluated cognitive function. Histological staining of brain tissues was conducted to assess brain injury, nuclear pyknosis, and iron accumulation. The activation of neurons, microglia, and astrocytes were detected using immunofluorescence staining. Neuron cell proliferation was measured using the Cell Counting Kit 8 (CCK-8). Quantitative PCR (qPCR) and western blot detected the mRNA and protein expression. Ferroptosis was assessed by measuring the accumulation of iron, malondialdehyde (MDA), superoxide dismutase (SOD), and ROS. The quantification of the N6-methyladenosine (m6A) RNA methylation levels in cells was quantified using the m6A-ELISA assay. Methylated RNA immunoprecipitation (MeRIP) assays were conducted to analyze the m6A modification on mRNA. The interaction between and mRNA was measured using RNA pulldown and RNA immunoprecipitation (RIP) assays.
expression was downregulated in TBI-injured brain tissues. Overexpression of improved cognitive function and brain recovery while simultaneously reducing ferroptosis and neuroinflammation. overexpression upregulated expression both and . Further studies indicated that m6A reader protein binds to mRNA, consequently mediating the -regulated m6A enrichment and RNA stability of . Knockdown of and treatment with ferroptosis inducer abolished the protective effects of on neurons.
exhibits anti-ferroptosis properties and promotes brain injury recovery after TBI by regulating the m6A modification and RNA stability of .
创伤性脑损伤（TBI）是一种由外力导致脑结构和功能受损的疾病。TBI后，铁蓄积和活性氧（ROS）增加会引发脂质过氧化，促进铁死亡。甲基转移酶样3（）通过调节相关信号通路抑制铁死亡。本研究探讨了对TBI中神经元铁死亡的影响，为新的见解和潜在治疗方法提供依据。
建立TBI小鼠和神经元细胞模型并用过表达进行处理。采用莫里斯水迷宫（MWM）试验评估认知功能。对脑组织进行组织学染色以评估脑损伤、核固缩和铁蓄积情况。使用免疫荧光染色检测神经元、小胶质细胞和星形胶质细胞的激活情况。使用细胞计数试剂盒8（CCK-8）测量神经元细胞增殖。定量聚合酶链反应（qPCR）和蛋白质免疫印迹法检测mRNA和蛋白质表达。通过测量铁、丙二醛（MDA）、超氧化物歧化酶（SOD）和ROS的蓄积情况评估铁死亡。使用m6A酶联免疫吸附测定法（m6A-ELISA）对细胞中N6-甲基腺苷（m6A）RNA甲基化水平进行定量。进行甲基化RNA免疫沉淀（MeRIP）试验以分析mRNA上的m6A修饰情况。使用RNA下拉和RNA免疫沉淀（RIP）试验测量与mRNA之间的相互作用。
在TBI损伤的脑组织中表达下调。过表达改善了认知功能和脑恢复，同时减少了铁死亡和神经炎症。过表达上调了和的表达。进一步研究表明，m6A阅读蛋白与mRNA结合，从而介导对的m6A富集调控和RNA稳定性。敲低并使用铁死亡诱导剂处理消除了对神经元的保护作用。
通过调节的m6A修饰和RNA稳定性表现出抗铁死亡特性，并促进TBI后脑损伤的恢复。
