Inhibiting neuronal AC1 for treating anxiety and headache in the animal model of migraine

Ren-Hao Liu; Mingjie Zhang; Man Xue; Tao Wang; Jing-Shan Lu; Xu-Hui Li; Yu-Xin Chen; Kexin Fan; Wantong Shi; Si-Bo Zhou; Qi-Yu Chen; Li Kang; Qian Song; Shengyuan Yu; Min Zhuo

doi:10.1016/j.isci.2023.106790

Inhibiting neuronal AC1 for treating anxiety and headache in the animal model of migraine

iScience. 2023 Apr 28;26(6):106790. doi: 10.1016/j.isci.2023.106790. eCollection 2023 Jun 16.

Authors

Ren-Hao Liu^{1

2

3}, Mingjie Zhang⁴, Man Xue^{1

2}, Tao Wang⁴, Jing-Shan Lu^{1

2}, Xu-Hui Li^{1

2}, Yu-Xin Chen^{1

2}, Kexin Fan^{1

2}, Wantong Shi^{1

2}, Si-Bo Zhou^{1

2}, Qi-Yu Chen^{1

2}, Li Kang⁴, Qian Song⁵, Shengyuan Yu⁴, Min Zhuo^{1

2}

Affiliations

¹ Institute of Brain Research, Qingdao International Academician Park, Qingdao 266000, China.
² Center for Neuron and Disease, Frontier Institutes of Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China.
³ School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.
⁴ Department of Neurology, the First Medical Centre, Chinese PLA General Hospital, Beijing 100853, China.
⁵ Neuroscience Research Center, Institute of Mitochondrial Biology and Medicine, Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Core Facilities Sharing Platform, Xi'an Jiaotong University, Xi'an 710049, China.

Abstract

Migraines are a common medical condition. From a basic science point of view, the central mechanism for migraine and headache is largely unknown. In the present study, we demonstrate that cortical excitatory transmission is significantly enhanced in the anterior cingulate cortex (ACC)-a brain region which is critical for pain perception. Biochemical studies found that the phosphorylation levels of both the NMDA receptor GluN2B and AMPA receptor GluA1 were enhanced in ACC of migraine rats. Both the presynaptic release of glutamate and postsynaptic responses of AMPA receptors and NMDA receptors were enhanced. Synaptic long-term potentiation (LTP) was occluded. Furthermore, behavioral anxiety and nociceptive responses were increased, which were reversed by application of AC1 inhibitor NB001 within ACC. Our results provide strong evidence that cortical LTPs contribute to migraine-related pain and anxiety. Drugs that inhibit cortical excitation such as NB001 may serve as potential medicines for treating migraine in the future.

Keywords: Molecular neuroscience; Pharmacology; Psychiatry.