title: Activation of GABAB2 subunits alleviates chronic cerebral hypoperfusion-induced anxiety-like behaviours: A role for BDNF signalling and Kir3 channels.
abstract: Anxiety is an affective disorder that is commonly observed after irreversible brain damage induced by cerebral ischemia and can delay the physical and cognitive recovery, which affects the quality of life of both the patient and family members. However, anxiety after ischemia has received less attention, and mechanisms underlying anxiety-like behaviours induced by chronic cerebral ischemia are under-investigated. In the present study, the chronic cerebral hypoperfusion model was established by the permanent occlusion of the bilateral common carotid arteries (two-vessel occlusion, 2VO) in rats, and anxiety-related behaviours were evaluated. Results indicated that 2VO induced obvious anxiety-like behaviours; the surface expressions of GABAB2 subunits were down-regulated; Brain derived neurotrophic factor (BDNF), tyrosine kinase B (TrkB) and neural cell adhesion molecule (NCAM) were reduced; Meanwhile, the surface expressions of G protein-activated inwardly rectifying potassium (GIRK, Kir3) channels were up-regulated in hippocampal CA1 in 2VO rats. Baclofen, a GABAB receptor agonist, significantly ameliorated the anxiety-like behaviours. It also improved the down-regulation of GABAB2 surface expressions, restored the levels of BDNF, TrkB and NCAM, and reversed the increased surface expressions of Kir3 in hippocampal CA1 in 2VO rats. However, the effects of baclofen were absent in shRNA-GABAB2 infected 2VO rats. These results suggested that activation of GABAB2 subunits could improve BDNF signalling and reverse Kir3 channel surface expressions in hippocampal CA1, which may alleviate the anxiety-like behaviours in rats with chronic cerebral hypoperfusion.
authors: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors: Yun
authors: Y
authors: Lu
authors: Neurology Department, Tongji Medical College, Huazhong University of Science and Technology, The Central Hospital of Wuhan, Wuhan 430030, China.
authors: Chang-Jun
authors: CJ
authors: Li
authors: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors: Cheng
authors: C
authors: Chen
authors: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors: Pan
authors: P
authors: Luo
authors: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors: Mei
authors: M
authors: Zhou
authors: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors: Cai
authors: C
authors: Li
authors: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Institute of Brain Research, Huazhong University of Science and Technology, Wuhan 430030, China.
authors: Xu-Lin
authors: XL
authors: Xu
authors: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Institute of Brain Research, Huazhong University of Science and Technology, Wuhan 430030, China.
authors: Qing
authors: Q
authors: Lu
authors: Department of Neuropsychopharmacology, Medical School of China Three Gorges University, Yichang 443002, China. Electronic address: hezhi2003@126.com.cn.
authors: Zhi
authors: Z
authors: He
authors: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Institute of Brain Research, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: ljguo@hust.edu.cn.
authors: Lian-Jun
authors: LJ
authors: Guo
mesh_terms: D000818:Animals; D001007:Anxiety / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D001418:Baclofen / Q000494:pharmacology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism; D002340:Carotid Artery Diseases / Q000188:drug therapy / Q000378:metabolism* / Q000523:psychology; D017536:Carotid Artery, Common; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000378:metabolism; D058786:GABA-B Receptor Agonists / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism; D011619:Psychotropic Drugs / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000378:metabolism; D018080:Receptors, GABA-B / Q000235:genetics / Q000378:metabolism*; D062827:Zonula Occludens-2 Protein / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D058786:GABA-B Receptor Agonists; C116566:Gabbr2 protein, rat; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; D011619:Psychotropic Drugs; D018080:Receptors, GABA-B; C477690:Snx27 protein, rat; C000606525:Tjp2 protein, rat; D062827:Zonula Occludens-2 Protein; C000621230:Ntrk2 protein, rat; D020813:Receptor, trkB; D001418:Baclofen
keywords: Anxiety-like behaviour; BDNF/TrkB/NCAM; Chronic cerebral hypoperfusion; GABA(B2) subunit; Kir3 channels