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瞬时受体电位香草酸亚型1(TRPV1)对癫痫大鼠脑海马突触可塑性的影响。

Effects of TRPV1 on the hippocampal synaptic plasticity in the epileptic rat brain.

作者信息

Saffarzadeh Fatemeh, Eslamizade Mohammad J, Ghadiri Tahereh, Modarres Mousavi Sayed Mostafa, Hadjighassem Mahmoudreza, Gorji Ali

机构信息

Department of Neuroscience, School of Medical Advanced Studies, Iran University of Medical Sciences, Tehran, Iran.

Shefa Neuroscience Research Center, Khatam-Al-Anbia Hospital, Tehran, Iran.

出版信息

Synapse. 2015 Jul;69(7):375-83. doi: 10.1002/syn.21825. Epub 2015 May 20.

Abstract

Temporal lobe epilepsy is often presented by medically intractable recurrent seizures due to dysfunction of temporal lobe structures, mostly the temporomesial structures. The role of transient receptor potential vaniloid 1 (TRPV1) activity on synaptic plasticity of the epileptic brain tissues was investigated. We studied hippocampal TRPV1 protein content and distribution in the hippocampus of epileptic rats. Furthermore, the effects of pharmacologic modulation of TRPV1 receptors on field excitatory postsynaptic potentials have been analyzed after induction of long term potentiation (LTP) in the hippocampal CA1 and CA3 areas after 1 day (acute phase) and 3 months (chronic phase) of pilocarpine-induced status epilepticus (SE). A higher expression of TRPV1 protein in the hippocampus as well as a higher distribution of this channel in CA1 and CA3 areas in both acute and chronic phases of pilocarpine-induced SE was observed. Activation of TRPV1 using capsaicin (1 µM) enhanced LTP induction in CA1 region in non-epileptic rats. Inhibition of TRPV1 by capsazepine (10 µM) did not affect LTP induction in non-epileptic rats. In acute phase of SE, activation of TRPV1 enhanced LTP in both CA1 and CA3 areas but TRPV1 inhibition did not affect LTP. In chronic phase of SE, application of TRPV1 antagonist enhanced LTP induction in CA1 and CA3 regions but TRPV1 activation had no effect on LTP. These findings indicate that a higher expression of TRPV1 in epileptic conditions is accompanied by a functional impact on the synaptic plasticity in the hippocampus. This suggests TRPV1 as a potential target in treatment of seizure attacks.

摘要

颞叶癫痫常因颞叶结构功能障碍,主要是颞叶内侧结构功能障碍,而出现药物难治性复发性癫痫发作。研究了瞬时受体电位香草酸受体1(TRPV1)活性对癫痫脑组织突触可塑性的作用。我们研究了癫痫大鼠海马中TRPV1蛋白的含量及分布。此外,在毛果芸香碱诱导的癫痫持续状态(SE)1天(急性期)和3个月(慢性期)后,在海马CA1和CA3区诱导长时程增强(LTP)后,分析了TRPV1受体的药理学调节对场兴奋性突触后电位的影响。观察到在毛果芸香碱诱导的SE急性期和慢性期,海马中TRPV1蛋白表达较高,且该通道在CA1和CA3区分布较多。使用辣椒素(1µM)激活TRPV1可增强非癫痫大鼠CA1区的LTP诱导。用辣椒素阻断剂(10µM)抑制TRPV1对非癫痫大鼠的LTP诱导无影响。在SE急性期,激活TRPV1可增强CA1和CA3区的LTP,但抑制TRPV1对LTP无影响。在SE慢性期,应用TRPV1拮抗剂可增强CA1和CA3区的LTP诱导,但激活TRPV1对LTP无影响。这些发现表明,癫痫状态下TRPV1的高表达伴随着对海马突触可塑性的功能影响。这表明TRPV1可能是治疗癫痫发作的潜在靶点。

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