DExH-box helicase 9 modulates hippocampal synapses and regulates neuropathic pain

Li Yang; Qiaoqiao Liu; Yaxuan Zhao; Ninghua Lin; Yue Huang; Qihui Wang; Kehui Yang; Runa Wei; Xiaotong Li; Ming Zhang; Lingyun Hao; Hongjun Wang; Zhiqiang Pan

doi:10.1016/j.isci.2024.109016

DExH-box helicase 9 modulates hippocampal synapses and regulates neuropathic pain

iScience. 2024 Jan 25;27(2):109016. doi: 10.1016/j.isci.2024.109016. eCollection 2024 Feb 16.

Authors

Li Yang^{1

2

3}, Qiaoqiao Liu^{1

2

3}, Yaxuan Zhao^{1

2

3}, Ninghua Lin⁴, Yue Huang^{1

2

3}, Qihui Wang^{1

2

3}, Kehui Yang^{1

2

3}, Runa Wei^{1

2

3}, Xiaotong Li^{1

2

3}, Ming Zhang^{1

2

3}, Lingyun Hao^{1

2

3}, Hongjun Wang^{1

2

3}, Zhiqiang Pan^{1

2

3}

Affiliations

¹ Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.
² Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.
³ NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou, Jiangsu 221004, China.
⁴ Department of Anesthesiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Zhongshan Road 321, Nanjing 210008, China.

Abstract

Experimental studies have shown that neuropathic pain impairs hippocampal synaptic plasticity. Here, we sought to determine the underlying mechanisms responsible for synaptic changes in neuropathic painful mouse hippocampal neurons. Beyond demonstrating proof-of-concept for the location of DExH-box helicase 9 (DHX9) in the nucleus, we found that it did exist in the cytoplasm and DHX9 depletion resulted in structural and functional changes at synapses in the hippocampus. A decrease of DHX9 was observed in the hippocampus after peripheral nerve injury; overexpression of DHX9 in the hippocampus significantly alleviated the nociceptive responses and improved anxiety behaviors. Mimicking DHX9 decrease evoked spontaneous pain behavioral symptoms and anxiety emotion in naïve mice. Mechanistically, we found that DHX9 bound to dendrin (Ddn) mRNA, which may have altered the level of synaptic- and dendritic-associated proteins. The data suggest that DHX9 contributes to synapses in hippocampal neurons and may modulate neuropathic pain and its comorbidity aversive emotion.

Keywords: Biological sciences; Natural sciences; Neuroscience; Pathophysiology; Physiology; Sensory neuroscience; Systems neuroscience.