title: Protection of stress-induced impairment of hippocampal/prefrontal LTP through blockade of glucocorticoid receptors: implication of MEK signaling.
abstract: 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.
authors.affiliation: INSERM, Physiopathologie des Maladies Psychiatriques, U894-7, Paris, France.
authors.forename: François
authors.initials: F
authors.lastname: Mailliet
authors.forename: Hongshi
authors.initials: H
authors.lastname: Qi
authors.forename: Cyril
authors.initials: C
authors.lastname: Rocher
authors.forename: Michael
authors.initials: M
authors.lastname: Spedding
authors.forename: Per
authors.initials: P
authors.lastname: Svenningsson
authors.forename: Thérèse M
authors.initials: TM
authors.lastname: Jay
mesh_terms: D000818:Animals; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D008297:Male; D015735:Mifepristone / Q000494:pharmacology / Q000627:therapeutic use; D020929:Mitogen-Activated Protein Kinase Kinases / Q000502:physiology*; D009434:Neural Pathways / Q000201:enzymology* / Q000503:physiopathology; D018384:Oxidative Stress / Q000187:drug effects*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors* / Q000502:physiology
chemical_list: D011965:Receptors, Glucocorticoid; D015735:Mifepristone; D020929:Mitogen-Activated Protein Kinase Kinases