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首页> 外文期刊>Neuroscience: An International Journal under the Editorial Direction of IBRO >LONG-TERM INHIBITION OF RHO-KINASE RESTORES THE LTP IMPAIRED IN CHRONIC FOREBRAIN ISCHEMIA RATS BY REGULATING GABA(A) AND GABA(B) RECEPTORS
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LONG-TERM INHIBITION OF RHO-KINASE RESTORES THE LTP IMPAIRED IN CHRONIC FOREBRAIN ISCHEMIA RATS BY REGULATING GABA(A) AND GABA(B) RECEPTORS

机译：通过调节GABA（A）和GABA（B）受体长期抑制Rho激酶恢复慢性前脑缺血大鼠LTP的恢复

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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.
机译：我们以前证明羟基法舒地尔灭活Rho激酶可能会影响海马体中的N-甲基-Daspartate（NMDA）兴奋性中间神经元，并减轻由慢性前脑灌注不足引起的大鼠的空间学习和记忆功能障碍。兴奋性神经递质谷氨酸和抑制性神经递质GABA之间的互补相互作用形成了突触可塑性和认知能力的分子基础。但是，尚不清楚GABA能抑制性中间神经元是否参与这些过程的基础机制。在这里，我们进一步检查了GABA能神经元在Rho激酶抑制剂的神经保护作用中的作用。 Wistar大鼠通过双侧颈总动脉闭塞（BCAO）诱发了慢性前脑缺血。在假手术或BCAO后30天评估海马CA3神经元的一般突触传递和长期增强（LTP）。进行实时PCR和蛋白质印迹分析，以确定Rho激酶抑制剂羟基法舒地尔对缺血后GABA能抑制性中间神经元表达和功能的影响。羟法舒地尔对一般突触传递没有显着影响，但可以消除对慢性前脑缺血诱导的LTP的抑制作用。此外，缺血后三个脑区的GABA（A）和GABA（B）的mRNA和蛋白水平显着降低，并且羟法舒地尔可以上调这些区域中除GABA（A）mRNA以外的所有mRNA和蛋白表达水平。大脑皮层和纹状体。使用针对GABA（A）和GABA（B）受体上特定位点的磷酸化抗体，我们进一步证明了羟基法舒地尔可以抑制theta爆破刺激触发的GABA能中神经元磷酸化。总之，我们的结果表明，Rho激酶的失活可以通过不同的机制增强GABA（A）和GABA（B）的表达，从而确保诱导海马LTP，并且可以降低GABA能抑制性中间神经元的磷酸化水平，从而促进海马LTP的磷酸化。 LTP诱导率和幅度，因此改善了慢性前脑缺血后遭受的认知缺陷。 （C）2014年IBRO。由Elsevier Ltd.出版。保留所有权利。

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