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Proteomic analysis of gene expression in the prefrontal cortex in infant rhesus macaques after multiple sevoflurane
Lingling Shi1, Zhenyu Xue1, Haoli Mao1
1Department of Anesthesiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, People's Republic of China.
Insights
Repeated sevoflurane exposure in infant macaques increases mitochondrial proteins in the brain. This may contribute to neurotoxicity and neurocognitive deficits observed later in life.
Area of Science:
- Neuroscience
- Biochemistry
- Toxicology
Background:
- Infant exposure to anesthetics like sevoflurane is linked to neurotoxicity.
- Neurocognitive impairment can result from early-life anesthetic exposure.
Purpose of the Study:
- To investigate the impact of repeated sevoflurane exposure on protein expression in infant rhesus macaque prefrontal cortex.
- To identify specific protein changes associated with sevoflurane-induced neurotoxicity.
Main Methods:
- Infant rhesus macaques received three sevoflurane exposures on postnatal days 7, 21, and 35.
- Quantitative proteomics (LC-MS with TMT10plex), western blotting, and transmission electron microscopy (TEM) were employed.
- Protein expression and mitochondrial morphology were analyzed.
Main Results:
- Proteomics revealed differential protein expression primarily related to mitochondrial respiration.
- Increased levels of NDUFA8 and COX IV proteins were observed in the prefrontal cortex post-sevoflurane exposure.
- Transmission electron microscopy showed no significant alterations in mitochondrial morphology.
Conclusions:
- Multiple sevoflurane exposures elevate mitochondrial protein levels in infant rhesus macaques.
- These protein changes suggest a specific impact on mitochondrial function.
- Further research is needed to fully understand the long-term consequences of these alterations.
Purpose:
Repeated exposure of infant rhesus macaques to sevoflurane induces neurotoxicity and is associated with neurocognitive impairment in later life. We aimed to investigate the effect of repeated sevoflurane exposure on the expression of proteins in the prefrontal cortex of infant rhesus macaques by proteomics.
Methods:
Rhesus macaques were exposed to sevoflurane three times, on postnatal days 7, 21 and 35. Quantitative proteomics employing LC-MS with isobaric labeling (TMT10plex), western blotting, and transmission electron microscopy (TEM) were utilized in the studies.
Results:
The results of a proteomics investigation of the brain revealed that the proteins that were differentially expressed in rhesus macaques after sevoflurane exposures were associated mainly with mitochondrial respiration. Following multiple sevoflurane exposures, the prefrontal cortices of rhesus macaques exhibited increases in NDUFA8 and COX IV protein levels, while no alterations in mitochondrial morphology were observed through TEM.
Conclusion:
Multiple exposures to sevoflurane increased the mitochondrial protein levels in rhesus macaques.
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