Fear extinction and BDNF: translating animal models of PTSD to the clinic.
Fear extinction and BDNF: translating animal models of PTSD to the clinic.
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DOI：
10.1111/j.1601-183x.2012.00801.x
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发表时间：
2012-07
期刊：
影响因子：
--
通讯作者：
Ressler KJ
中科院分区：
文献类型：
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作者：
Andero R;Ressler KJ
脑源性神经营养因子(BDNF)是研究最多的神经营养因子，参与长期学习和记忆所需的突触可塑性过程。具体地说，BDNF基因表达及其高亲和力TrkB受体的激活在杏仁核、海马体和前额叶皮质是形成包括恐惧记忆在内的情感记忆所必需的。在恐惧处理过程改变的精神障碍中，有创伤后应激障碍(PTSD)，其特征是无法消除恐惧记忆。由于BDNF似乎增强了恐惧的消退，通过BDNF信号针对PTSD等焦虑症患者受损的消退可能是提高治疗效果的一种重要而新颖的方法。这篇综述的目的是提供一个翻译观点，该观点源于BDNF对突触可塑性和恐惧消退的调节。此外，还有一些不同的系统似乎可以通过BDNF调节来改变恐惧的消退，比如内源性大麻系统和下丘脑-垂体肾上腺轴(HPA)。最近的工作还发现，脑源性神经营养因子激活的上游的垂体腺苷酸环化酶激活多肽(PACAP)和PAC1受体可能与创伤后应激障碍有关。尤其有趣的是，有数据表明，外源性恐惧消退增强剂，如抗抑郁剂、组蛋白去乙酰酶抑制剂(HDACi)和D-环丝氨酸(部分NMDA激动剂)，可能通过BDNF-TrkB系统起作用或与之协同作用。最后，我们回顾了重组BDNF和一种可能的TrkB激动剂7，8-DHF可以增强恐惧消退的研究。这些方法可能会导致新的制剂，改善动物模型的灭绝，并最终改善人类的灭绝。
Brain-derived neurotrophic factor (BDNF) is the most studied neurotrophin involved in synaptic plasticity processes that are required for long-term learning and memory. Specifically, BDNF gene expression and activation of its high-affinity TrkB receptor are necessary in the amygdala, hippocampus and prefrontal cortex for the formation of emotional memories, including fear memories. Among the psychiatric disorders with altered fear processing there is Post-traumatic Stress Disorder (PTSD) which is characterized by an inability to extinguish fear memories. Since BDNF appears to enhance extinction of fear, targeting impaired extinction in anxiety disorders such as PTSD via BDNF signalling may be an important and novel way to enhance treatment efficacy. The aim of this review is to provide a translational point of view that stems from findings in the BDNF regulation of synaptic plasticity and fear extinction. In addition, there are different systems that seem to alter fear extinction through BDNF modulation like the endocannabionoid system and the hypothalamic-pituitary adrenal axis (HPA). Recent work also finds that the pituitary adenylate cyclase-activating polypeptide (PACAP) and PAC1 receptor, which are upstream of BDNF activation, may be implicated in PTSD. Especially interesting are data that exogenous fear extinction enhancers such as antidepressants, histone deacetylases inhibitors (HDACi) and D-cycloserine, a partial NMDA agonist, may act through or in concert with the BDNF-TrkB system. Finally, we review studies where recombinant BDNF and a putative TrkB agonist, 7,8-DHF, may enhance extinction of fear. These approaches may lead to novel agents that improve extinction in animal models and eventually humans.