Ketamine destabilizes growth of dendritic spines in developing hippocampal neurons in vitro via a Rho‑dependent mechanism

Jiang,Sufang; Hao,Zimiao; Li,Xuze; Bo,Lijun; Zhang,Rui; Wang,Ying; Duan,Xiaofeng; Kang,Rongtian; Huang,Lining

doi:10.3892/mmr.2018.9531

Ketamine destabilizes growth of dendritic spines in developing hippocampal neurons in vitro via a Rho‑dependent mechanism

Authors:
- Sufang Jiang
- Zimiao Hao
- Xuze Li
- Lijun Bo
- Rui Zhang
- Ying Wang
- Xiaofeng Duan
- Rongtian Kang
- Lining Huang
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Affiliations: Department of Anesthesiology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China
Published online on: October 2, 2018 https://doi.org/10.3892/mmr.2018.9531
Pages: 5037-5043
Copyright: © Jiang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The safety of anesthetics on the developing brain has caused concern. Ketamine, an N‑methyl‑D‑aspartate receptor antagonist, is widely used as a general pediatric anesthetic. Recent studies suggested that ketamine alters the plasticity of dendritic spines in the developing brain and may be an important contributing factor to learning and cognitive impairment. However, the underlying molecular mechanism remains poorly understood. Therefore, the aim of the present study was to investigate the effect of ketamine on the plasticity of dendritic spines in cultured hippocampal neurons and the potential underlying mechanisms. After 5 days in vitro, rat hippocampal neurons were exposed to different concentrations (100, 300 and 500 µM) of ketamine for 6 h. Ketamine decreased the number and length of dendritic spines in a dose‑dependent manner. Ketamine at a concentration of 300 µM caused an upregulation of transforming protein RhoA (RhoA) and Rho‑associated kinase (ROCK) protein. These effects were inhibited by the ROCK inhibitor Y27632. These results suggested that ketamine induces loss and shortening of dendritic spines in hippocampal neurons via activation of the RhoA/ROCK signaling pathway.

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