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
Affiliations
Ren-Hao Liu
Institute of Brain Research, Qingdao International Academician Park, Qingdao 266000, China; Center for Neuron and Disease, Frontier Institutes of Science and Technology, Xi’an Jiaotong University, Xi’an 710049, China; School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China
Mingjie Zhang
Department of Neurology, the First Medical Centre, Chinese PLA General Hospital, Beijing 100853, China
Man Xue
Institute of Brain Research, Qingdao International Academician Park, Qingdao 266000, China; Center for Neuron and Disease, Frontier Institutes of Science and Technology, Xi’an Jiaotong University, Xi’an 710049, China
Tao Wang
Department of Neurology, the First Medical Centre, Chinese PLA General Hospital, Beijing 100853, China
Jing-Shan Lu
Institute of Brain Research, Qingdao International Academician Park, Qingdao 266000, China; Center for Neuron and Disease, Frontier Institutes of Science and Technology, Xi’an Jiaotong University, Xi’an 710049, China
Xu-Hui Li
Institute of Brain Research, Qingdao International Academician Park, Qingdao 266000, China; Center for Neuron and Disease, Frontier Institutes of Science and Technology, Xi’an Jiaotong University, Xi’an 710049, China
Yu-Xin Chen
Institute of Brain Research, Qingdao International Academician Park, Qingdao 266000, China; Center for Neuron and Disease, Frontier Institutes of Science and Technology, Xi’an Jiaotong University, Xi’an 710049, China
Kexin Fan
Institute of Brain Research, Qingdao International Academician Park, Qingdao 266000, China; Center for Neuron and Disease, Frontier Institutes of Science and Technology, Xi’an Jiaotong University, Xi’an 710049, China
Wantong Shi
Institute of Brain Research, Qingdao International Academician Park, Qingdao 266000, China; Center for Neuron and Disease, Frontier Institutes of Science and Technology, Xi’an Jiaotong University, Xi’an 710049, China
Si-Bo Zhou
Institute of Brain Research, Qingdao International Academician Park, Qingdao 266000, China; Center for Neuron and Disease, Frontier Institutes of Science and Technology, Xi’an Jiaotong University, Xi’an 710049, China
Qi-Yu Chen
Institute of Brain Research, Qingdao International Academician Park, Qingdao 266000, China; Center for Neuron and Disease, Frontier Institutes of Science and Technology, Xi’an Jiaotong University, Xi’an 710049, China
Li Kang
Department of Neurology, the First Medical Centre, Chinese PLA General Hospital, Beijing 100853, China
Qian Song
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
Shengyuan Yu
Department of Neurology, the First Medical Centre, Chinese PLA General Hospital, Beijing 100853, China; Corresponding author
Min Zhuo
Institute of Brain Research, Qingdao International Academician Park, Qingdao 266000, China; Center for Neuron and Disease, Frontier Institutes of Science and Technology, Xi’an Jiaotong University, Xi’an 710049, China; Corresponding author
Summary: 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.
