Unraveling the signaling network between dysregulated microRNA and mRNA expression in sevoflurane-induced developmental neurotoxicity in rat
Yuanyuan Wang,
Xin Men,
Xiaodong Huang,
Xiaoxiao Qiu,
Weilong Wang,
Jin Zhou,
Zhenfeng Zhou
Affiliations
Yuanyuan Wang
Department of Endocrinology, Xixi Hospital of Hangzhou (Affiliated Hangzhou Xixi Hospital of Zhejiang Chinese Medical University), Hangzhou, China
Xin Men
Department of Anesthesiology, Hangzhou Women's Hospital (Hangzhou Maternity and Child Health Care Hospital, Hangzhou First People's Hospital Qianjiang New City Campus, Zhejiang Chinese Medical University), Hangzhou, China
Xiaodong Huang
Department of Anesthesiology, Hangzhou Women's Hospital (Hangzhou Maternity and Child Health Care Hospital, Hangzhou First People's Hospital Qianjiang New City Campus, Zhejiang Chinese Medical University), Hangzhou, China
Xiaoxiao Qiu
Department of Anesthesiology, Hangzhou Women's Hospital (Hangzhou Maternity and Child Health Care Hospital, Hangzhou First People's Hospital Qianjiang New City Campus, Zhejiang Chinese Medical University), Hangzhou, China
Weilong Wang
Department of Anesthesiology, Hangzhou Women's Hospital (Hangzhou Maternity and Child Health Care Hospital, Hangzhou First People's Hospital Qianjiang New City Campus, Zhejiang Chinese Medical University), Hangzhou, China
Jin Zhou
Department of Anesthesiology, Hangzhou Women's Hospital (Hangzhou Maternity and Child Health Care Hospital, Hangzhou First People's Hospital Qianjiang New City Campus, Zhejiang Chinese Medical University), Hangzhou, China
Zhenfeng Zhou
Department of Anesthesiology, Hangzhou Women's Hospital (Hangzhou Maternity and Child Health Care Hospital, Hangzhou First People's Hospital Qianjiang New City Campus, Zhejiang Chinese Medical University), Hangzhou, China; Corresponding author. Hangzhou Women's Hospital, No.369 Kunpeng Road, Hangzhou, Zhejiang, 310018, China.
Research has indicated that general anesthesia may cause neuroapoptosis and long-term cognitive dysfunction in developing animals, however, the precise mechanisms orchestrating these outcomes remain inadequately elucidated within scholarly discourse. The purpose of this study was to investigate the impact of sevoflurane on the hippocampus of developing rats by analyzing the changes in microRNA and mRNA and their interactions. Rats were exposed to sevoflurane for 4 h on their seventh day after birth, and the hippocampus was collected for analysis of neuroapoptosis by Western blot and immunohistochemistry. High-throughput sequencing was conducted to analyze the variances in miRNA and mRNA expression levels, and the Morris water maze was employed to assess long-term memory in rats exposed to sevoflurane after 8 weeks. The results showed that sevoflurane exposure led to dysregulation of 5 miRNAs and 306 mRNAs in the hippocampus. Bioinformatic analysis revealed that these dysregulated miRNA-mRNA target pairs were associated with pathological neurodevelopment and developmental disorders, such as regulation of axonogenesis, regulation of neuron projection development, regulation of neuron differentiation, transmission of nerve impulse, and neuronal cell body. Further analysis showed that these miRNAs formed potential network interactions with 44 mRNAs, and two important nodes were identified, miR-130b-5p and miR-449c-5p. Overall, this study suggests that the dysregulation of the miRNA-mRNA signaling network induced by sevoflurane may contribute to neurodevelopmental toxicity in the hippocampus of rats and be associated with long-term cognitive dysfunction.
