The Mechanism Of Synaptic Homeostasis In Juvenile Mice Under The Intervention Of Sevoflurane

Anesthesia drugs and anesthesia techniques have been in clinical practice for more than a hundred years.With the rise of the field of anesthesia,a large number of surgical operations have been carried out.Countless patients can complete operations in a state of low responsiveness.Avoid unnecessary pain.However,with the increase in clinical practice,anesthetics itself,as a drug,has certain toxicity to organs including the brain,heart,liver,and blood vessels.Among them,the relationship between receiving anesthetics and neurotoxicity in infants and young children has received a lot of attention.Especially after a child receives general anesthesia for the first time,symptoms such as night terrors,anxiety,bedwetting,cognitive changes,and sleep-wake cycle changes may appear.This has further prompted the U.S.Food and Drug Administration to clearly state in its 2016 report: “The repeated or prolonged use of general anesthesia and sedative drugs for children under three years of age or pregnant women in the third trimester of surgery may affect children.The development of the brain.” Unfortunately,so far,there is still a lack of systematic research and elaboration on this neurotoxicity research.The vast majority of studies still focus on clinical reports.Scattered literature points out that multiple anesthesia in the young period of mice may cause behavioral changes in mice,such as anxiety,depression,mental retardation,and impulsive behavior.And a period of time after anesthesia,it can be observed that cell apoptosis in the prefrontal cortex,hippocampus and other areas increases,proliferation decreases,and the number of neuronal synapses decreases.There is a demand of more detailed research and experimental evidence for the three stages of awake-anesthesia-wake-up after anesthesia.This focuses on the changes in synaptic-related protein content and phosphorylation modification levels in the three stages of wakefulness-anesthesiaawakening after anesthesia and combined with the "Phosphorylation/Dephosphorylation cycle regulation" proposed by the sleep field in 2017 The new regulation theory of sleep molecules introduces this new sleep-wake mechanism into the three stages of wake-up,anesthesia,and wake-up after anesthesia.First,we combined the existing literature to establish a sevoflurane-mediated recovery model from anesthesia in juvenile mice.The synaptic components of this model were quickly extracted,and it was found that the phosphorylation level of total protein on the synapse increased significantly during anesthesia and recovered during the recovery process after anesthesia,but it was not completely reversible.Therefore,we use proteomics and phosphorylated proteomics to conduct a more in-depth analysis of this process.We found that approximately 457 proteins on synapses and864 phosphorylation sites fluctuate significantly.There is a strong correlation between changes in protein levels and circadian rhythms.After that,we used IGPS software to establish the mapping relationship between phosphorylation sites and differential kinases,and further discovered two genes inherited from the X chromosome,Cdkl5 and Cask.The relationship between the two and X-linked intellectual disability has been reported in large numbers.In summary,our research focuses on the frontiers of the field of anesthesia,introducing a new regulatory mechanism in the field of sleep,guiding us to solve the current clinical urgent need to clarify problems,and aiming to screen for neurotoxic factors related to juvenile anesthesia.