• Yulim Lee, Jun Young Heo, Xianshu Ju, Jianchen Cui, Min Jeong Ryu, Min Joung Lee, Boohwi Hong, Sungho Yoo, Jeonghoon Ahn, Yoon Hee Kim, Youngkwon Ko, and Woosuk Chung.
• Department of Biochemistry, Chungnam National University School of Medicine, Daejeon, South Korea; Department of Medical Science, Chungnam National University School of Medicine, Daejeon, South Korea; Infection Control Convergence Research Center, Chungnam National University School of Medicine, Daejeon, South Korea.
• Neurotoxicology. 2021 Jan 1; 82: 1-8.

AbstractGeneral anesthesia induces changes in dendritic spine number and synaptic transmission in developing mice. These changes are rather disturbing, as similar changes are seen in animal models of neurodevelopmental disorders. We previously suggested that mTor-dependent upregulation of mitochondrial function may be involved in such changes. To further understand the significance of mitochondrial changes after general anesthesia during neurodevelopment, we exposed young mice to 2.5 % sevoflurane for 2 h followed by injection of rotenone, a mitochondrial complex I inhibitor. In postnatal day 17 (PND17) mice, intraperitoneal injection of rotenone not only blocked sevoflurane-induced increases in mitochondrial function, it also prevented sevoflurane-induced changes in excitatory synaptic transmission. Interestingly, similar changes were not observed in younger, neonatal mice (PND7). We next assessed whether the mitochondrial unfolded protein response (UPRmt) acted as a link between anesthetic exposure and mitochondrial function. Expression of UPRmt proteins, which help maintain protein-folding homeostasis and increase mitochondrial function, was increased 6 h after sevoflurane exposure. Our results show that a single, brief sevoflurane exposure induces age-dependent changes in mitochondrial function that constitute an important mechanism for the increase in excitatory synaptic transmission in late postnatal mice, and also suggest mitochondria and UPRmt as potential targets for preventing anesthesia toxicity.Copyright © 2020 Elsevier B.V. All rights reserved.

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