Uncovering the Role of FBXO22 in Anesthesia-induced Cognitive Dysfunction in Adult Mice

Published on November 8, 2022

Think of the brain like a complex cityscape and anesthesia as a gust of wind that rearranges the buildings. A recent study delves into the effects of propofol, a commonly used anesthetic, on the cognitive function and synaptic plasticity in adult mice. The researchers found that repeated exposure to propofol led to cognitive impairment in these rodents. To understand the underlying mechanisms, they investigated various aspects of neuronal activity, including changes in synaptic proteins, dendritic spine density, and synaptic transmission. In their exploration, they discovered a protein called FBXO22, which plays a critical role in this process. By silencing FBXO22, they were able to partially reverse the effects of propofol on neuronal function and cognitive abilities. These findings highlight the involvement of FBXO22 in regulating anesthesia-induced changes in cognitive function and synaptic plasticity. By further studying this protein, scientists may uncover potential therapeutic targets to mitigate anesthesia side effects and improve patient outcomes.

Recent observation demonstrated that prolonged anesthesia modifies brain synaptic architecture in all ages, including adult. Propofol is the most commonly utilized anesthetics at clinic. Whether repeated administration of propofol modulates cognitive impairment in adults and changes synaptic plasticity remains, however, to be explored. In this study, we first discovered that repeated and prolonged exposure to propofol-induced cognitive impairment in adult rodents. Then, we examined the property of hippocampal primary neurons and slices after propofol treatment in mice, including synaptic protein profile, dendritic spine density, as well as synaptic transmission. We found the distinctive change of the F-box only protein 22 (FBXO22), an F-box E3 ligase, during this process and further explored its role. Knockdown experiments showed the downregulation of FBXO22 restored the changes by propofol treatment on hippocampal primary neurons and attenuated propofol-induced hippocampal dependent cognitive dysfunction. Our results showed that FBXO22 is involved in the regulation of repeated propofol treatment induced changes of synaptic plasticity and cognitive dysfunction in adult mice. Repeated propofol treatment leads to cognitive dysfunction by regulating FBXO22 in adult rodents.

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