Cerqueira João J, Mailliet François, Almeida Osborne F X, Jay Thérèse M, Sousa Nuno
Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal.
J Neurosci. 2007 Mar 14;27(11):2781-7. doi: 10.1523/JNEUROSCI.4372-06.2007.
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.
关于压力对大脑有害影响的研究主要集中在海马体。由于前额叶皮质（PFC）功能障碍是许多与压力相关疾病的特征，我们在此分析了慢性应激对大鼠海马体 - 前额叶皮质通路完整性的影响，并通过行为、电生理功能和形态学评估进行监测。我们发现，慢性应激通过降低海马体 - 前额叶皮质连接中的长时程增强（LTP）诱导来损害突触可塑性；此外，它会导致前额叶皮质内选择性萎缩，并严重破坏工作记忆和行为灵活性，这两种功能依赖于前额叶皮质的完整性。我们还证明，短期应激暴露在影响依赖前额叶皮质的任务之前会诱导空间参考记忆缺陷，因此表明海马体到前额叶皮质连接内的突触可塑性受损与应激诱导的前额叶皮质功能障碍有关。这些发现证明了前额叶皮质在对压力的适应不良反应中的重要作用，并确定该区域是应激相关疾病干预的靶点。
