Excessive corticosterone induces excitotoxicity of hippocampal neurons and sensitivity of potassium channels via insulin-signaling pathway
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Corticosterone (CORT) is a kind of corticosteroid produced by cortex of adrenal glands. Hypothalamic–pituitary–adrenal (HPA) axis hyperfunction leads to excessive CORT, which is associated with depression. Few studies have investigated the role of CORT in voltage-gated ion channels and its upstream signaling pathway in central nervous system. In this study, we investigated the mechanism of excessive CORT resulting in brain impairment on voltage-gated ion channels, and its upstream signaling effectors in hippocampal CA1 neurons. The action potential (AP) and voltage-gated potassium currents were determined by using whole-cell patch-clamp. Insulin and CORT improved the neuronal excitability. Independent effects existed in transient potassium channel (IA) and delay rectifier potassium channel (IK). The inhibition of potassium currents, IA in our experiment, could increase neuronal excitability. CORT led to the excitotoxicity of hippocampal neurons via phosphatidylinositol 3 kinase (PI3K)-mediated insulin-signaling pathway. Therefore, the stimulation of excessive CORT induces excitotoxicity of hippocampal neurons and sensitivity of potassium channels via PI3K-mediated insulin-signaling pathway, which indicates one possible way of depression treatment.
KeywordsCorticosterone Voltage-gated potassium channel Insulin-signaling pathway Hippocampal neurons
This study was supported by grants from the National Natural Science Foundation of China (81571804, 81771979).
Zhuo Yang, Qingqing Xia and Hui Wang conceived the study and designed the experiments. Qingqing Xia performed all experiments and data analysis, wrote the manuscript and generated the figures. Hongqiang Yin provided the guidance of technique and data analysis. All authors have read and approved the manuscript.
Compliance with ethical standards
All animal experiments were approved by the Animal Research Ethics Committee, School of Medicine, Nankai University and were performed in accordance with the Animal Management Rules of the Ministry of Health of the People’s Republic of China.
Conflict of interest
The authors declare that they have no conflict of interest.
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