Kozlovsky Nitsan, Matar Michael A, Kaplan Zeev, Kotler Moshe, Zohar Joseph, Cohen Hagit
Ministry of Health Beer-Sheva Mental Health Center, Anxiety and Stress Research Unit, Faculty of Health Sciences, Ben-Gurion University of the Negev, Israel.
Int J Neuropsychopharmacol. 2007 Dec;10(6):741-58. doi: 10.1017/S1461145707007560. Epub 2007 Feb 12.
Brain-derived neurotrophic factor (BDNF) and its intracellular kinase-activating receptor TrkB, have been implicated in the neurobiological mechanisms underlying the clinical manifestations of PTSD, especially those related to synaptic efficacy and neural plasticity. BDNF interacts with components of the stress response such as corticosterone, and plays an important role in growth, maintenance and functioning of several neuronal systems. This study employed an animal model of PTSD to investigate the relationship between prevalence rates of distinct patterns of behavioural responses to predator stress, circulating levels of corticosterone and local levels of mRNA for BDNF, TrkB and two other neurotrophic factors in selected brain areas. Animals whose behaviour was extremely disrupted by exposure selectively displayed significant down-regulation of mRNA for BDNF and up-regulation of TrkB mRNA in the CA1 subregion of the hippocampus, compared to animals whose behaviour was minimally or partially affected and to unexposed controls. The response was consistent throughout the entire study only in CA1. The consistent long-term the BDNF down-regulation and TrkB up-regulation associated with extreme behavioural compromise may be associated with chronic stress-induced psychopathological processes, especially in the hippocampus. The corresponding changes in neural plasticity and synaptic functioning may mediate clinical manifestations of PTSD.
脑源性神经营养因子（BDNF）及其细胞内激酶激活受体TrkB，已被认为与创伤后应激障碍（PTSD）临床表现背后的神经生物学机制有关，尤其是那些与突触效能和神经可塑性相关的机制。BDNF与应激反应的成分如皮质酮相互作用，并在多个神经元系统的生长、维持和功能中发挥重要作用。本研究采用PTSD动物模型，以研究对捕食者应激的不同行为反应模式的发生率、循环皮质酮水平以及选定脑区中BDNF、TrkB和其他两种神经营养因子的局部mRNA水平之间的关系。与行为受到最小或部分影响的动物以及未暴露的对照组相比，行为因暴露而受到极大干扰的动物在海马体CA1亚区选择性地表现出BDNF mRNA的显著下调和TrkB mRNA的上调。整个研究过程中，只有在CA区域的反应是一致的。与极端行为受损相关的BDNF持续长期下调和TrkB上调可能与慢性应激诱导的精神病理过程有关，尤其是在海马体中。神经可塑性和突触功能的相应变化可能介导PTSD的临床表现。
