Background/Aims: Multiple exposures to anesthesia in children may increase the risk of developing cognitive impairment. Sevoflurane is an anesthetic that is commonly used in children during surgery. Cyclin-dependent kinase (CDK) 5 is involved in the regulation of sevoflurane-induced cognitive dysfunction, but the mechanistic details remain unclear. The present study evaluated the mechanism by which CDK5 mediates sevoflurane-induced cognitive dysfunction in mice. Methods: Hippocampal neurons were isolated from postnatal day 0 C57BL/6 mouse pups. Six-day-old wild-type mice were exposed to sevoflurane and then treated with the CDK5 inhibitor roscovitine. The effects on cognitive function were evaluated with the Morris water maze and neuronal damage in the hippocampus was assessed by immunohistochemical analysis. Results: CDK5 activation increased neuronal damage by inducing Tau/glycogen synthase kinase (GSK) 3 beta and suppressing extracellular signal-regulated kinase (ERK)/peroxisome proliferator-activated receptor (PPAR)gamma/cyclic AMP response element-binding protein (CREB) signaling following exposure to sevoflurane. CDK5 inhibition by roscovitine administration alleviated sevoflurane-induced neuronal damage and cognitive impairment. Conclusions: Inhibiting CDK5 with roscovitine has neuroprotective effects against neuronal injury and cognitive dysfunction caused by sevoflurane anesthesia that are exerted via modulation of Tau/GSK3 beta and ERK/PPAR gamma/CREB signaling. (C) 2017 The Author(s) Published by S. Karger AG, Basel
[1]Tongji Univ, Tongji Med Sch, Shanghai Tongji Hosp, Dept Anesthesiol, Shanghai, Peoples R China.
[2]Fudan Univ, Huadong Hosp, Dept Anesthesiol, Shanghai, Peoples R China.
[3]Tongji Univ, Shanghai Tongji Hosp, Tongji Med Sch, Dept Emergency Internal Med, Shanghai, Peoples R China.
[4]Tongji Univ, Shanghai Tongji Hosp, Tongji Med Sch, Dept Sci Res Management, Shanghai, Peoples R China.
[5]Tongji Univ, Shanghai Tongji Hosp, Tongji Med Sch, Dept Psychol, Shanghai, Peoples R China.
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