rTMS Ameliorates PTSD Symptoms in Rats by Enhancing Glutamate Transmission and Synaptic Plasticity in the ACC via the PTEN/Akt Signalling Pathway
rTMS Ameliorates PTSD Symptoms in Rats by Enhancing Glutamate Transmission and Synaptic Plasticity in the ACC via the PTEN/Akt Signalling Pathway
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rTMS 通过 PTEN/Akt 信号通路增强 ACC 中的谷氨酸传输和突触可塑性，从而改善大鼠的 PTSD 症状
DOI：
10.1007/s12035-017-0602-7
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Qingrong Tan
中科院分区：
文献类型：
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作者：
Gaohua Liu;Dayun Feng;Jian Wang;Haifeng Zhang;Zhengwu Peng;Min Cai;Jing Yang;Ruiguo Zhang;Huaning Wang;Shengxi Wu;Qingrong Tan
重复经颅磁刺激(RTMS)是一种新型的生理学疗法，已被用于临床治疗精神障碍。我们先前的研究表明rTMS对创伤后应激障碍(PTSD)有潜在的治疗作用。然而，确切的分子机制尚不清楚。目前，我们采用单次延长应激(SPS)大鼠PTSD模型，观察SPS诱导后大鼠扣带回前部(ACC)谷氨酸能传递和神经可塑性的变化，探讨rTMS的保护作用及其机制。我们发现，高频rTMS(HrTMS，15赫兹)通过显著增加NMDAR和AMPAR的表达，显著缓解SPS治疗后ACC中受损的谷氨酸能受体。同时，HrTMS通过减少PTEN的表达和增加Akt的磷酸化抑制了SPS处理后ACC中10号染色体上的神经元性磷酸酶和张力蛋白同源物(PTEN)/Akt的信号转导，Akt磷酸化是影响记忆和突触可塑性的关键因素。应用PTEN抑制剂BPV、小干扰RNA和Akt抑制剂Wortmannin对SPS治疗后的ACC进行立体定位，以推进机制研究。免疫印迹、双重免疫荧光、高尔基染色和行为学分析表明，rTMS对SPS诱导的PTEN/Akt激活、谷氨酸受体表达、神经元突触可塑性和PTSD相关行为的影响可被PTEN抑制增强，而在ACC中被Akt抑制阻断。我们的研究为rTMS治疗PTSD的有效性提供了令人信服的证据，并提示其潜在的机制涉及通过PTEN/Akt信号通路重塑神经元突触可塑性。
Repetitive transcranial magnetic stimulation (rTMS) is a novel physiological therapy that has been adopted to clinically treat psychiatric disorders. Our previous study indicated the potential therapeutic effect of rTMS on posttraumatic stress disorder (PTSD). However, the exact molecular mechanism is elusive. Currently, using the single prolonged stress (SPS) rat model for PTSD, we investigated the glutamatergic transmission and neural plasticity changes in the anterior cingulate cortex (ACC) after SPS induction and explored the protective effects and mechanism of rTMS treatment. We found that high-frequency rTMS (HrTMS, 15 Hz) treatment significantly relieved the impaired glutamatergic receptors in the ACC after SPS treatment by significantly increasing NMDAR and AMPAR expression. Simultaneously, HrTMS blocked inhibited neuronal phosphatase and tensin homologue on chromosome 10 (PTEN)/Akt signalling in the ACC after SPS treatment by decreasing PTEN expression and increasing Akt phosphorylation, which is critically involved in the regulation of memory and synaptic plasticity. The PTEN inhibitors bpV and small interfering RNA and the Akt inhibitor wortmannin were stereotaxically administered to the ACC after SPS treatment to advance the mechanistic study. Analysis by Western blot, double immunofluorescence, Golgi staining and behavioural tests demonstrated that the effects of rTMS on PTEN/Akt activation, glutamatergic receptor expression, neuronal synaptic plasticity and PTSD-related behaviours induced by SPS treatment were enhanced by PTEN inhibition and blocked by Akt inhibition in the ACC. Our study provides convincing evidence for the effectiveness of rTMS treatment on PTSD and suggests that its potential mechanism involves remodelling neuronal synaptic plasticity via the PTEN/Akt signalling pathway.