Format

Send to

Choose Destination
Brain Res. 2019 May 1;1710:188-198. doi: 10.1016/j.brainres.2018.12.010. Epub 2018 Dec 7.

Sevoflurane-induced learning deficits and spine loss via nectin-1/corticotrophin-releasing hormone receptor type 1 signaling.

Author information

1
Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin Research Institute of Anesthesiology, Tianjin 300052, China.
2
Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin Research Institute of Anesthesiology, Tianjin 300052, China. Electronic address: wangguolinemail@126.com.

Abstract

In recent years, the neurotoxicity of general anesthetics in the developing brain has been studied and raised great concern as a major health issue to the public and physicians. Sevoflurane inhalation may induce neurotoxicity expressed as memory and learning impairment in young animals. In the current study, we investigated the role of nectin-1 and corticotrophin-releasing hormone receptor type 1 (CRHR1) in sevoflurane-induced learning deficits and dendritic spines loss in neonatal mice. Neonatal mice (P7) were treated with 3% sevoflurane with 60% O2 or 60% O2 for 6 h. Cognitive function was evaluated by Y Maze, Object recognition test, and Morris Water Maze. Hippocampal nectin-1 and L-afadin expression assessed using western blot analysis. The dendritic spines morphology of the hippocampus was determined using Golgi impregnation on 7 d and 2 months old. Sevoflurane exposed to neonatal mice decreased hippocampal nectin-1 levels from 1 h to 2 months after sevoflurane inhalation and attenuated working and spatial memory and spinal number in adulthood, which could be reversed by nectin-1 overexpression and CRHR1 antagonist Antalarmin. Nectin-1 knockdown caused spatial learning deficits and dendritic spine loss and lower L-afadin protein expression. Sevoflurane-induced nectin-1 and L-afadin expression decrease was mediated by CRHR1 signaling in the hippocampus. This information can be used to develop targeted intervention aimed at decreasing the neurotoxicity of sevoflurane inhalation.

KEYWORDS:

Corticotrophin-releasing hormone receptor type 1 (CRHR1); Nectin-1; Neurotoxicity; Sevoflurane

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center