Mailliet François, Qi Hongshi, Rocher Cyril, Spedding Michael, Svenningsson Per, Jay Thérèse M
INSERM, Physiopathologie des Maladies Psychiatriques, U894-7, Paris, France.
Exp Neurol. 2008 Jun;211(2):593-6. doi: 10.1016/j.expneurol.2008.02.030. Epub 2008 Mar 16.
We previously reported that exposure to acute and chronic stress impairs long-term potentiation (LTP) in the hippocampal-prefrontal cortex pathway and showed evidence for a fundamental role of the prefrontal cortex in maladaptive responses to stress. The goal of the current studies was to examine whether blockade of glucocorticosteroid receptors (GR), by mifepristone (a Type II glucocorticoid receptor antagonist), just after exposure to acute stress could prevent stress-induced impairment of prefrontal LTP. We further examine the effects of mifepristone on mitogen-activated protein/ERK kinase (MEK) signaling pathway in the prefrontal cortex. The data show that an acute injection of mifepristone after stress restored the stress-induced blockade of prefrontal LTP and reduction of phospho-Ser217/221-MEK. These findings have significance for the treatment of memory deficits in hypercortisolemic states, such as stress and depression.
我们之前报道过，暴露于急性和慢性应激会损害海马体-前额叶皮层通路中的长时程增强（LTP），并表明前额叶皮层在对应激的适应不良反应中起重要作用。当前研究的目的是检验在暴露于急性应激后，米非司酮（一种II型糖皮质激素受体拮抗剂）阻断糖皮质激素受体（GR）是否能预防应激诱导的前额叶LTP损伤。我们进一步研究了米非司酮对前额叶皮层中丝裂原活化蛋白/细胞外信号调节激酶（MEK）信号通路的影响。数据显示，应激后急性注射米非司酮可恢复应激诱导的前额叶LTP阻断以及磷酸化Ser217/221-MEK的减少。这些发现对于治疗高皮质醇血症状态下的记忆缺陷具有重要意义，如应激和抑郁症。
