Protection conferred by Corticotropin-releasing hormone in rat primary cortical neurons against chemical ischemia involves opioid receptor activation.
Different studies have supported neuroprotective effects of Corticotropin-releasing hormone (CRH) against various excitotoxic and oxidative insults in vitro. However, the physiological mechanisms involved in this protection remain largely unknown. The present study was undertaken to determine the impact of CRH administration (at concentrations ranging from 200 fmol to 2 nmol) before and at delayed time intervals following potassium cyanide (KCN)-induced insult in rat primary cortical neurons. A second objective aimed to determine whether kappa and delta opioid receptor (KOR and DOR) blockade, using nor-binaltorphimine and naltrindole respectively (10 microM), could alter CRH-induced cellular protection. Our findings revealed that CRH treatments before or 3 and 8 h following KCN insult conferred significant protection against cortical injury, an effect blocked in cultures treated with alpha-helical CRH (9-41) prior to KCN administration. In addition, KOR and DOR blockade significantly reduced CRH-induced neuronal protection observed 3 but not 8 h post-KCN insult. Using western blotting, we demonstrated increased dynorphin, enkephalin, DOR and KOR protein expression in CRH-treated primary cortical neurons, and immunocytochemistry revealed the presence of opioid peptides and receptors in cortical neurons. These findings suggest protective effects of CRH against KCN-induced neuronal damage, and the contribution of the opioid system in modulating CRH actions.
Charron
Charlaine
C
School of Psychology, University of Ottawa, 11, Marie Curie, Vanier 204, Ottawa, ON, Canada.
Schock
Sarah C
SC
Proulx
Geneviève
G
Thompson
Charlie S
CS
Hakim
Antoine M
AM
Plamondon
Hélène
H
D000818:Animals; D002545:Brain Ischemia; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage*; D004399:Dynorphins / Q000187:drug effects / Q000378:metabolism; D004745:Enkephalins / Q000378:metabolism; D007211:Indoles / Q000378:metabolism; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D011190:Potassium Cyanide / Q000633:toxicity; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors / Q000378:metabolism
D004745:Enkephalins; D007211:Indoles; D009292:Narcotic Antagonists; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; C051844:norbinaltorphimine; C007293:DAPI; D009271:Naltrexone; D004399:Dynorphins; D003346:Corticotropin-Releasing Hormone; C055382:naltrindole; D011190:Potassium Cyanide