title: Clonidine ameliorates cognitive impairment induced by chronic cerebral hypoperfusion via up-regulation of the GABABR1 and GAD67 in hippocampal CA1 in rats.
abstract: Chronic cerebral hypoperfusion may cause cognitive impairment, but the underlying neurobiological mechanism is poorly understood. In this study, we investigated whether clonidine, an α2-adrenergic receptor agonist, could play neuroprotective role against chronic ischemic brain injury and the potential mechanism. Rats were subjected to permanent bilateral occlusion of the common carotid arteries (two-vessel occlusion, 2VO). Three weeks later, rats were administrated with 0.05mg/kg clonidine (intraperitoneal injection, i.p.) for 7days. Cognitive function was evaluated by Morris water maze (MWM). Immunofluorescence and western blots were used to detect the protein levels. Our results showed that the cognitive function was partially impaired, and the expression of neuronal nuclei (NeuN), glutamic acid decarboxylase 67 (GAD67) and γ-aminobutyric acid-B receptor 1 (GABABR1) in hippocampal CA1 area was attenuated after 2VO, which were not observed in CA3 and dentate gyrus (DG). Administration of 0.05mg/kg clonidine (i.p.) for 7days could improve cognitive function and the expression of NeuN, GAD67 and GABABR1 in CA1, but did not affect the protein levels in CA3 and DG. These findings demonstrated that clonidine could ameliorate cognitive deficits and neuronal impairment induced by chronic cerebral hypoperfusion via up-regulation of GABABR1 and GAD67 in hippocampal CA1.
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: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors: Changjun
authors: C
authors: Li
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: 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: Pengcheng
authors: P
authors: Huang
authors: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors: Jiahong
authors: J
authors: Tan
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 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: Xulin
authors: X
authors: Xu
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: Lianjun
authors: L
authors: Guo
keywords: Clonidine; GABA(B)R1; GAD67; NeuN; Two-vessel occlusion