Long-lasting hippocampal synaptic protein loss in a mouse model of posttraumatic stress disorder.
Long-lasting hippocampal synaptic protein loss in a mouse model of posttraumatic stress disorder.
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DOI：
10.1371/journal.pone.0042603
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Schmidt U
中科院分区：
文献类型：
--
作者：
Herrmann L;Ionescu IA;Henes K;Golub Y;Wang NX;Buell DR;Holsboer F;Wotjak CT;Schmidt U
尽管进行了大量的研究工作，但创伤后应激障碍（PTSD）的分子发病机制，特别是在大多数患有这种焦虑症的患者中发现的海马体积损失仍然是难以捉摸的。我们之前证明了创伤诱导的海马萎缩也可以在表现出PTSD样综合征的小鼠中观察到。为了破译这些跨物种的创伤后海马改变的分子相关性，我们比较了一组神经结构标志物蛋白的表达水平创伤和对照小鼠在不同的时间点后，他们受到电击或模拟治疗，然后在几个实验组的压力再曝光。据我们所知，这是第一个系统的在体研究分析长期的神经分子后遗症急性创伤应激与再暴露。我们在这里表明，PTSD样综合征的小鼠是伴随着一个持久的减少海马突触蛋白，有趣的是与强度的广义和条件性恐惧反应，但不与强度的过度觉醒症状。此外，我们证明了用5-羟色胺再摄取抑制剂（SSRI）氟西汀治疗能够抵消PTSD样综合征和创伤后突触蛋白丢失。总之，这项研究首次证明了海马突触蛋白的丢失与小鼠PTSD样综合征有关。进一步的研究将揭示这些发现是否可以转移到PTSD患者身上。
Despite intensive research efforts, the molecular pathogenesis of posttraumatic stress disorder (PTSD) and especially of the hippocampal volume loss found in the majority of patients suffering from this anxiety disease still remains elusive. We demonstrated before that trauma-induced hippocampal shrinkage can also be observed in mice exhibiting a PTSD-like syndrome. Aiming to decipher the molecular correlates of these trans-species posttraumatic hippocampal alterations, we compared the expression levels of a set of neurostructural marker proteins between traumatized and control mice at different time points after their subjection to either an electric footshock or mock treatment which was followed by stressful re-exposure in several experimental groups. To our knowledge, this is the first systematic in vivo study analyzing the long-term neuromolecular sequelae of acute traumatic stress combined with re-exposure. We show here that a PTSD-like syndrome in mice is accompanied by a long-lasting reduction of hippocampal synaptic proteins which interestingly correlates with the strength of the generalized and conditioned fear response but not with the intensity of hyperarousal symptoms. Furthermore, we demonstrate that treatment with the serotonin reuptake inhibitor (SSRI) fluoxetine is able to counteract both the PTSD-like syndrome and the posttraumatic synaptic protein loss. Taken together, this study demonstrates for the first time that a loss of hippocampal synaptic proteins is associated with a PTSD-like syndrome in mice. Further studies will have to reveal whether these findings are transferable to PTSD patients.
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