Department of Physiology and Biophysics, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14214, USA.
Mol Psychiatry. 2011 Feb;16(2):156-70. doi: 10.1038/mp.2010.50. Epub 2010 May 11.
Corticosteroid stress hormones have a strong impact on the function of prefrontal cortex (PFC), a central region controlling cognition and emotion, though the underlying mechanisms are elusive. We found that behavioral stressor or short-term corticosterone treatment in vitro induces a delayed and sustained potentiation of the synaptic response and surface expression of N-methyl-D-aspartic acid receptors (NMDARs) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) in PFC pyramidal neurons through a mechanism depending on the induction of serum- and glucocorticoid-inducible kinase (SGK) and the activation of Rab4, which mediates receptor recycling between early endosomes and the plasma membrane. Working memory, a key function relying on glutamatergic transmission in PFC, is enhanced in acutely stressed animals through an SGK-dependent mechanism. These results suggest that acute stress, by activating glucocorticoid receptors, increases the trafficking and function of NMDARs and AMPARs through SGK/Rab4 signaling, which leads to the potentiated synaptic transmission, thereby facilitating cognitive processes mediated by the PFC.
皮质甾类应激激素对控制认知和情绪的前额叶皮层（PFC）的功能有很大的影响，但潜在的机制尚不清楚。我们发现，行为应激源或体外短期皮质酮处理通过一种依赖于血清和糖皮质激素诱导激酶（SGK）的诱导和 Rab4 的激活的机制，诱导 PFC 锥体神经元中 N-甲基-D-天冬氨酸受体（NMDAR）和 α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPAR）的突触反应和表面表达的延迟和持续增强，Rab4 介导了受体在早期内体和质膜之间的再循环。工作记忆是一种依赖于 PFC 中谷氨酸传递的关键功能，通过 SGK 依赖的机制在急性应激动物中增强。这些结果表明，急性应激通过激活糖皮质激素受体，通过 SGK/Rab4 信号增加 NMDAR 和 AMPAR 的转运和功能，从而增强突触传递，从而促进由 PFC 介导的认知过程。
