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学科主题: 临床医学
题名:
LONG-TERM INHIBITION OF RHO-KINASE RESTORES THE LTP IMPAIRED IN CHRONIC FOREBRAIN ISCHEMIA RATS BY REGULATING GABA(A) AND GABA(B) RECEPTORS
作者: Huang, L.1; Zhao, L. B.1; Yu, Z. Y.1; He, X. J.2; Ma, L. P.2; Li, N.2; Guo, L. J.3; Feng, W. Y.1
关键词: Rho-kinase ; hydroxyfasudil ; chronic forebrain ischemia ; LTP ; GABA(A) ; GABA(B)
刊名: NEUROSCIENCE
发表日期: 2014-09-26
DOI: 10.1016/j.neuroscience.2014.07.015
卷: 277, 页:383-391
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Neurosciences
研究领域[WOS]: Neurosciences & Neurology
关键词[WOS]: FOCAL CEREBRAL-ISCHEMIA ; NEURONAL DAMAGE ; ROCK INHIBITOR ; BLOOD-FLOW ; IN-VIVO ; FASUDIL ; MEMORY ; BRAIN ; POTENTIATION ; ACTIVATION
英文摘要:

We previously demonstrated that inactivation of Rho-kinase by hydroxyfasudil could impact N-methyl-Daspartate (NMDA) excitatory interneurons in the hippocampus and attenuate the spatial learning and memory dysfunction of rats caused by chronic forebrain hypoperfusion ischemia. Complementary interactions between the excitatory neurotransmitter glutamate and the inhibitory neurotransmitter GABA form the molecular basis of synaptic plasticity and cognitive performance. However, whether the GABAergic inhibitory interneurons are involved in the mechanisms underlying these processes remains unclear. Here, we further examined the role of GABAergic interneurons in the neuroprotective effect of the Rho-kinase inhibitor. Chronic forebrain ischemia was induced in Wistar rats by bilateral common carotid artery occlusion (BCAO). The general synaptic transmission and long-term potentiation (LTP) of hippocampal CA3 neurons were evaluated at 30 days after sham surgery or BCAO. Real-time PCR and Western blot analyses were conducted to determine the effect of the Rho-kinase inhibitor hydroxyfasudil on GABAergic inhibitory interneuron expression and function after ischemia. Hydroxyfasudil showed no significant effect on general synaptic transmission, but it could abolish the inhibition of LTP induced by chronic forebrain ischemia. Moreover, the mRNA and protein levels of GABA(A) and GABA(B) in three brain regions after ischemia were markedly decreased, and hydroxyfasudil could up-regulate all mRNA and protein expression levels in these areas except for GABA(A) mRNA in the cerebral cortex and striatum. Using phosphorylation antibodies against specific sites on the GABA(A) and GABA(B) receptors, we further demonstrated that hydroxyfasudil could inhibit GABAergic interneuron phosphorylation triggered by the theta burst stimulation. In summary, our results indicated that the inactivation of Rho-kinase could enhance GABA(A) and GABA(B) expressions by different mechanisms to guarantee the induction of hippocampal LTP, and it could decrease the phosphorylation level of GABAergic inhibitory interneurons to promote the LTP induction rate and magnitude, hence improving the cognitive deficit suffered after chronic forebrain ischemia. (C) 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

语种: 英语
所属项目编号: 81200887
项目资助者: National Natural Science Foundation of China
WOS记录号: WOS:000341488700036
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/65303
Appears in Collections:北京大学第二临床医学院_药剂科_期刊论文

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作者单位: 1.Peking Univ, Peoples Hosp, Dept Pharm, Beijing 100044, Peoples R China
2.Peking Univ, Peoples Hosp, Cent Lab, Beijing 100044, Peoples R China
3.Huazhong Univ Sci & Technol, Tongji Med Coll, Sch Basic Med Sci, Dept Pharmacol, Wuhan 430030, Peoples R China

Recommended Citation:
Huang, L.,Zhao, L. B.,Yu, Z. Y.,et al. LONG-TERM INHIBITION OF RHO-KINASE RESTORES THE LTP IMPAIRED IN CHRONIC FOREBRAIN ISCHEMIA RATS BY REGULATING GABA(A) AND GABA(B) RECEPTORS[J]. NEUROSCIENCE,2014,277:383-391.
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