期刊
MOLECULAR PSYCHIATRY
卷 16, 期 2, 页码 156-170出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/mp.2010.50
关键词
acute stress; corticosterone; NMDA receptors; AMPA receptors; SGK; Rab4; working memory
资金
- NIH
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 alpha-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. Molecular Psychiatry (2011) 16, 156-170; doi:10.1038/mp.2010.50; published online 11 May 2010
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