title: Anticonvulsant effect of a ghrelin receptor agonist in 6Hz corneally kindled mice.
abstract: Ghrelin has anticonvulsant and neuroprotective effects in models of chemoconvulsant-induced seizures and status epilepticus. In this study we investigated whether deletion of the ghrelin receptor could alter the kindling process in the 6 Hz corneal kindling model and whether ghrelin receptor ligands possess anticonvulsant effects in fully kindled mice. Ghrelin receptor wild-type and knockout mice were electrically stimulated at a subconvulsive current twice daily via corneal electrodes until they reached the fully kindled state. Mice lacking the ghrelin receptor showed similar seizure severity during kindling acquisition as well as in the maintenance phase when compared to their wild-type littermates. Subsequently we proceeded by investigating possible anticonvulsant effects of the ghrelin receptor ligands in the acute 6 Hz seizure model and the fully 6 Hz kindled mice. The ghrelin receptor agonist JMV-1843 decreased the seizure severity score both in acutely 6 Hz stimulated mice and in fully kindled ghrelin receptor wild-type mice, but not in fully kindled ghrelin receptor knockout mice. No effect on seizure severity was observed following the ghrelin receptor antagonist JMV-2959 in both models. This finding indicates that JMV-1843 exerts an anticonvulsant effect in kindled mice via the ghrelin receptor.
authors.affiliation: Center for Neurosciences, VUB Free University Brussels, Brussels, Belgium.
authors.forename: Jessica
authors.initials: J
authors.lastname: Coppens
authors.affiliation: Center for Neurosciences, VUB Free University Brussels, Brussels, Belgium.
authors.forename: Najat
authors.initials: N
authors.lastname: Aourz
authors.affiliation: Center for Neurosciences, VUB Free University Brussels, Brussels, Belgium.
authors.forename: Laura
authors.initials: L
authors.lastname: Walrave
authors.affiliation: IBMM Institute of Biomolecules Max Mousseron, University of Montpellier, Montpellier, France.
authors.forename: Jean-Alain
authors.initials: JA
authors.lastname: Fehrentz
authors.affiliation: IBMM Institute of Biomolecules Max Mousseron, University of Montpellier, Montpellier, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Martinez
authors.affiliation: Center for Neurosciences, VUB Free University Brussels, Brussels, Belgium.
authors.forename: Dimitri
authors.initials: D
authors.lastname: De Bundel
authors.affiliation: Center for Neurosciences, VUB Free University Brussels, Brussels, Belgium.|Department of Neurology, UZ Gent, Ghent, Belgium.
authors.forename: Jeanelle
authors.initials: J
authors.lastname: Portelli
authors.affiliation: Center for Neurosciences, VUB Free University Brussels, Brussels, Belgium.
authors.forename: Ilse
authors.initials: I
authors.lastname: Smolders
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D003315:Cornea / Q000294:innervation*; D004195:Disease Models, Animal; D004558:Electric Stimulation / Q000009:adverse effects; D005998:Glycine / Q000031:analogs & derivatives / Q000627:therapeutic use; D007211:Indoles; D007696:Kindling, Neurologic / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009842:Oligopeptides / Q000627:therapeutic use; D054440:Receptors, Ghrelin / Q000819:agonists* / Q000172:deficiency / Q000235:genetics; D013226:Status Epilepticus / Q000188:drug therapy* / Q000235:genetics; D014230:Triazoles / Q000627:therapeutic use; D014364:Tryptophan / Q000031:analogs & derivatives
chemical_list: D000927:Anticonvulsants; D007211:Indoles; C569751:N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminoacetamide; D009842:Oligopeptides; D054440:Receptors, Ghrelin; D014230:Triazoles; C582727:macimorelin; D014364:Tryptophan; D005998:Glycine
keywords: 6 Hz kindling; Ghrelin; Ghrelin receptor; JMV-1843; JMV-2959