Jianhui Liu1, Junjun Yang1, Yinhua Xu2, Gang Guo3, Li Cai4, Heng Wu5, Yanhong Zhao1, Xiaoqing Zhang1. 1. Department of Anesthesiology, Shanghai Tongji Hospital, Tongji Medical School, Tongji University, Shanghai, China. 2. Department of Anesthesiology, Huadong Hospital Affiliated to Fudan University, Shanghai, China. 3. Department of Emergency Internal Medicine, Shanghai Tongji Hospital, Tongji Medical School, Tongji University, Shanghai, China. 4. Department of Scientific Research Management, Shanghai Tongji Hospital, Tongji Medical School, Tongji University, Shanghai, China. 5. Department of Psychology, Shanghai Tongji Hospital, Tongji Medical School, Tongji University, Shanghai, China.
Abstract
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) 3β and suppressing extracellular signal-regulated kinase (ERK)/peroxisome proliferator-activated receptor (PPAR)γ/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/GSK3β and ERK/PPARγ/CREB signaling.
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) 3β and suppressing extracellular signal-regulated kinase (ERK)/peroxisome proliferator-activated receptor (PPAR)γ/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/GSK3β and ERK/PPARγ/CREB signaling.
Authors: Simon C Johnson; Amanda Pan; Grace X Sun; Arielle Freed; Julia C Stokes; Rebecca Bornstein; Michael Witkowski; Li Li; Jeremy M Ford; Christopher R A Howard; Margaret M Sedensky; Philip G Morgan Journal: PLoS One Date: 2019-03-21 Impact factor: 3.240
Authors: Hamad Yadikar; Isabel Torres; Gabrielle Aiello; Milin Kurup; Zhihui Yang; Fan Lin; Firas Kobeissy; Richard Yost; Kevin K Wang Journal: PLoS One Date: 2020-07-21 Impact factor: 3.240