Protection of stress-induced impairment of hippocampal/prefrontal LTP through blockade of glucocorticoid receptors: implication of MEK signaling.
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.
Mailliet
François
F
INSERM, Physiopathologie des Maladies Psychiatriques, U894-7, Paris, France.
Qi
Hongshi
H
Rocher
Cyril
C
Spedding
Michael
M
Svenningsson
Per
P
Jay
Thérèse M
TM
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
D011965:Receptors, Glucocorticoid; D015735:Mifepristone; D020929:Mitogen-Activated Protein Kinase Kinases