Establishing an agenda for translational research on PTSD
Establishing an agenda for translational research on PTSD
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DOI：
10.1196/annals.1364.023
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发表时间：
2006-01-01
期刊：
影响因子：
--
通讯作者：
McEwen, Bruce S.
中科院分区：
文献类型：
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作者：
Miller, Melinda M.;McEwen, Bruce S.
对与精神疾病有关的大脑机制进行动物研究是一项巨大的挑战，因为不可能在大鼠或小鼠身上精确地模拟人类疾病的症状。然而，只要认识到动物模型的局限性，动物模型还是有用处的。与创伤后应激障碍（PTSD）相关的动物研究指出，急性和慢性应激源，如约束或固定作为最相关的刺激来研究神经和内分泌系统如何受到即时和长期的影响。特别相关的是压力源对大脑中负责情绪记忆的区域，如杏仁核、前额叶皮层和海马体的影响的开始和持续时间。海马体在记忆和身体的营养功能中起作用。海马体接收来自杏仁核的输入，其空间记忆功能被杏仁核活动改变。大鼠反复应激抑制齿状回神经发生，导致海马和内侧前额皮质神经元树突萎缩。相反，它会导致基底外侧杏仁核神经元的树突复杂性增加，并产生新的突触。反复的压力也会增加恐惧和攻击性，减少空间记忆，改变情境恐惧条件反射。抗抑郁药和情绪稳定剂对这些过程有不同的影响。新的数据表明，单次应激事件可以导致基底外侧杏仁核突触形成的延迟改变，而不会改变树突的长度和分支。进一步的研究正在探讨单一创伤应激源导致的前额皮质和海马的结构变化，这可能反映了与杏仁核的功能相互作用。以及对作用的机械研究。肾上腺糖皮质激素和儿茶酚胺，这些结果可能告诉我们，大脑是如何被急性和反复的无法控制的压力塑造的，然后可以在人类焦虑症中进行研究。
Animal research on, brain mechanisms involved in psychiatric disorders' presents an enormous challenge because it is impossible to precisely, model symptoms of, a human disorder in a rat or mouse. Nevertheless, there are uses for animal models as long as the limitations are recognized. Animal research related to posttraumatic stress disorder (PTSD) points, to acute and chronic stressors, such as restraint or immobilization as being the most relevant stimuli to study how neural and endocrine systems-are affected, both immediately and long term. Of particular relevance are the onset,and duration of effects of stressors on brain areas subserving emotional memories, such as the amygdala, prefrontal cortex, and hippocampus The hippocampus, plays a role in memory and in vegetative functions of the body. The hippocampus receives input from the amygdala and its function in spatial memory is altered by amygdala activity. Repeated-stress in the rat suppresses dentate gyrus neurogenesis and causes dendrites, of hippocampal and medial prefrontal cortical neurons to shrink. Conversely, it causes basolateral amygdala neurons to increase in dendritic complexity and sprout new synapses. Repeated stress also increases fear and aggression, reduces spatial memory, and alters contextual fear conditioning. Antidepressants and mood stabilizers have diverse effects on these processes. New data indicate that a single stress episode can cause a delayed alteration in synapse formation in the basolateral amygdala without changing dendritic length and branching. Further studies are examining the structural changes in prefrontal cortex and hippocampus as a result of single traumatic stressors, which may reflect the functional interactions with the amygdala. Together with mechanistic studies of the role of. adrenal glucocorticoids and catecholamines, these results may tell,us how the brain is shaped,by acute and repeated uncontrollable stress in ways that then can be investigated in human anxiety disorders.