Capsaicin exhibits neuroprotective effects in a model of transient global cerebral ischemia in Mongolian gerbils.
1. Capsaicin, the irritant principle of hot peppers, is a vanilloid agonist known to activate the transient receptor potential channel vanilloid subfamily member 1 (VR1), recently reported to be involved in neurodegeneration. The present study investigated the role of VR1 in a model of global cerebral ischemia in gerbils. 2. Over the dose range tested, capsaicin (0.01, 0.025, 0.05, 0.2 and 0.6 mg kg(-1)), given 5 min after recirculation, dose-dependently antagonized the ischemia-induced electroencephalographic total spectral power decrease and restored relative frequency band distribution evaluated 7 days after ischemia. 3. Capsaicin, at all tested doses, fully prevented ischemia-induced hyperlocomotion evaluated 1 day after ischemia. 4. Capsaicin dose-dependently antagonized ischemia-induced memory impairment evaluated in a passive avoidance task, 3 days after ischemia. 5. Capsaicin showed a dose-dependent hypothermic effect evaluated for 2 h after recirculation. 6. At 7 days after ischemia, a progressive survival of pyramidal cells in the CA1 subfield in capsaicin-treated gerbils, with a maximum of 80%, at a dose of 0.2 mg kg(-1), was obtained. 7. The selective VR1 antagonist, capsazepine (0.01 mg kg(-1)), reversed capsaicin-induced protective effects, in a competitive manner. 8. These results suggest that the neuroprotective effect of capsaicin may be attributable, at least in part, to VR1 desensitization and provide a valuable target for development of interventional pharmacological strategies.
Pegorini
Simona
S
Department of Pharmacology, Chemotherapy and Medical Toxicology, University of Milan, Via Vanvitelli 32, 20129 Milan, Italy.
Braida
Daniela
D
Verzoni
Chiara
C
Guerini-Rocco
Chiara
C
Consalez
Gian Giacomo
GG
Croci
Laura
L
Sala
Mariaelvina
M
D000818:Animals; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004569:Electroencephalography; D005849:Gerbillinae; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000188:drug therapy*; D008297:Male; D008568:Memory / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000473:pathology; D011955:Receptors, Drug / Q000819:agonists / Q000037:antagonists & inhibitors
D018696:Neuroprotective Agents; D011955:Receptors, Drug; C071423:capsazepine; D002211:Capsaicin