The prefrontal cortex as a key target of the maladaptive response to stress
The prefrontal cortex as a key target of the maladaptive response to stress
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DOI：
10.1523/jneurosci.4372-06.2007
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发表时间：
2007-03-14
影响因子：
5.3
通讯作者：
Sousa, Nuno
中科院分区：
文献类型：
--
作者：
Cerqueira, Joao J.;Mailliet, Francois;Sousa, Nuno
关于压力对大脑有害影响的研究主要集中在海马体上。由于前额叶皮质(PFC)功能障碍是许多应激相关疾病的特征，我们通过行为和电生理功能以及形态学评估，分析了慢性应激对大鼠海马-PFC通路完整性的影响。我们发现，慢性应激通过减少海马-PFC连接中LTP的诱导来损害突触的可塑性；此外，它还诱导PFC内的选择性萎缩，并严重破坏工作记忆和行为灵活性，这两个功能依赖于PFC的完整性。我们还证明，短时间的应激暴露在影响PFC依赖的任务之前会导致空间参考记忆障碍，从而表明海马到PFC连接中突触可塑性的损害与应激诱导的PFC功能障碍有关。这些发现证明了PFC在压力适应不良反应中的基本作用，并将该区域确定为干预应激相关障碍的目标。
Research on the detrimental effects of stress in the brain has mainly focused on the hippocampus. Because prefrontal cortex (PFC) dysfunction characterizes many stress-related disorders, we here analyzed the impact of chronic stress in rats on the integrity of the hippocampal - PFC pathway, monitored by behavioral and electrophysiological function and morphological assessment. We show that chronic stress impairs synaptic plasticity by reducing LTP induction in the hippocampal - PFC connection; in addition, it induces selective atrophy within the PFC and severely disrupts working memory and behavioral flexibility, two functions that depend on PFC integrity. We also demonstrate that short periods of stress exposure induce spatial reference memory deficits before affecting PFC-dependent tasks, thus suggesting that the impairment of synaptic plasticity within the hippocampus-to-PFC connection is of relevance to the stress-induced PFC dysfunction. These findings evidence a fundamental role of the PFC in maladaptive responses to stress and identify this area as a target for intervention in stress-related disorders.