In vivo administration of corticotropin-releasing hormone at remote intervals following ischemia enhances CA1 neuronal survival and recovery of spatial memory impairments: a role for opioid receptors.
The contribution of corticotropin-releasing hormone (CRH) in the modulation of ischemia-induced cell death in vivo remains unclear. We characterized the impact of pre-ischemic administration of CRH (0, 0.1, 1, 5 microg, i.c.v., 15 min prior to vessel occlusion) on neuronal damage following global ischemia in rats. The injection of 5 microg CRH led to a 37% increase in CA1 neuronal survival compared to vehicle-treated ischemic animals, while pre-treatment with alpha-helical CRH (9-41) abolished this neuronal protection. A second objective aimed to determine whether CRH protection is maintained over weeks when the peptide is administered at remote time intervals following ischemia. Compared to vehicle-treated ischemic animals, administration of CRH 8h following global ischemia led to a 61% increase in CA1 neuronal survival observed 30 days post-ischemia. Neuronal protection translated into significant improvement of ischemia-induced spatial memory deficits in the radial maze. Finally, our findings demonstrated that selective blockade of kappa- and delta-opioid receptors (using nor-binaltorphimine and naltrindole, respectively) prior to CRH administration significantly reduced CA1 neuronal protection. These findings represent the first demonstration of enhanced neuronal survival following in vivo CRH administration in a global model of ischemia in rats. They also support the idea that CRH-induced neuroprotection involves opioid receptors activation.
Charron
Charlaine
C
University of Ottawa, School of Psychology, 11, Marie Curie, Vanier Building, Room 204, Ottawa, ON K1N 9A9, Canada.
Fréchette
Sabrina
S
Proulx
Geneviève
G
Plamondon
Hélène
H
D000704:Analysis of Variance; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D016923:Cell Death / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D007276:Injections, Intraventricular; D008297:Male; D018782:Maze Learning / Q000502:physiology; D009410:Nerve Degeneration / Q000378:metabolism / Q000517:prevention & control*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors / Q000378:metabolism; D013997:Time Factors
D018696:Neuroprotective Agents; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D003346:Corticotropin-Releasing Hormone