General anesthesia activates the mitochondrial unfolded protein response and induces age-dependent, long-lasting changes in mitochondrial function in the developing brain
| Autor: | Sungho Yoo, Yoon Hee Kim, Jianchen Cui, Boohwi Hong, Min Jeong Ryu, Jun Young Heo, Woosuk Chung, Yulim Lee, Xianshu Ju, Min Joung Lee, Jeonghoon Ahn, Youngkwon Ko |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
Patch-Clamp Techniques Dendritic spine Anesthesia General Biology Mitochondrion Neurotransmission Toxicology Sevoflurane Mice 03 medical and health sciences Oxygen Consumption 0302 clinical medicine Rotenone Mitochondrial unfolded protein response medicine Animals skin and connective tissue diseases 030304 developmental biology 0303 health sciences General Neuroscience Age Factors Neurotoxicity Brain medicine.disease Mitochondria Mice Inbred C57BL Anesthesia Anesthetics Inhalation Anesthetic Unfolded Protein Response Unfolded protein response sense organs 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | NeuroToxicology. 82:1-8 |
| ISSN: | 0161-813X |
| DOI: | 10.1016/j.neuro.2020.10.012 |
| Popis: | General 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect