期刊
NEUROPHARMACOLOGY
卷 118, 期 -, 页码 242-250出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2017.03.014
关键词
Hippocampus; Endothelin1; Anxiety; Neuron excitability
资金
- National Natural Science Foundation of China [81200119, 31600970]
- Fundamental Research Funds for the Central Universities [2042016kf0036]
- funds for Luojia Young Scholars of Wuhan University
- Natural Science Foundation of Hubei Province [2016CFB247]
Anxiety disorders contribute to the pathophysiology of psychiatric diseases, including major depression, substance abuse, and schizophrenia. The hippocampus is important for anxiety modulation. However, the mechanisms that control the neuronal activity of the hippocampus in anxiety are still not clear. We found that Endothelin-1 (ET1) mRNA in the hippocampus was down-regulated in high-anxiety mice. Neutralizing endogenous ET1 in the hippocampal CM enhanced anxiety-like behaviors. We next revealed that most expression of ET1 and its receptors in the CA1 takes place in pyramidal neurons, and the ET1 signaling pathway directly regulated the excitability of CM pyramidal neurons and glutamatergic synaptic neurotransmission. Finally, we proved that neutralizing endogenous CA1 ET1 produces anxiogenic effects on low-anxiety mice, whereas infusing exogenous ET1 into the CA1 alleviates the anxiety susceptibility of high-anxiety mice. Together, these results indicate that ET1 signaling is critical in maintaining the excitability of glutamatergic neurons in the hippocampus and, thus, in modulating anxiety-like behaviors. Because ET1 is a risk factor for ischemic stroke, our findings might also help to explain the potential mechanism of emotional abnormality in stroke. (C) 2017 Elsevier Ltd. All rights reserved.
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