Neuropeptide Y delays hippocampal kindling in the rat.
Chronic intrahippocampal infusion of the neurotrophin brain-derived neurotrophic factor (BDNF) has been shown to delay kindling epileptogenesis in the rat and several lines of evidence suggest that neuropeptide Y could mediate these inhibitory effects. Chronic infusion of BDNF leads to a sustained overexpression of neuropeptide Y in the hippocampus, which follows a time course similar to that of the suppressive effects of BDNF on kindling. In vivo, acute applications of neuropeptide Y or agonists of its receptors exert anticonvulsant properties, especially on seizures of hippocampal origin. In this study, we examined how chronic infusion of this neuropeptide in the hippocampus affected kindling epileptogenesis. A 7-day continuous infusion of neuropeptide Y in the hippocampus delayed the progression of hippocampal kindling in the rat, whereas anti-neuropeptide Y immunoglobulins had an aggravating effect. These results show that neuropeptide Y exerts anti-epileptogenic properties on seizures originating within the hippocampus and lend support to the hypothesis that BDNF delays kindling at least in part through upregulation of this neuropeptide. They also suggest that the seizure-induced upregulation of neuropeptide Y constitutes an endogenous mechanism counteracting excessive hippocampal excitability.
Reibel
Sophie
S
INSERM U398, Faculté de Medecine, Strasbourg Cedex, France. Reibel@lyon.inserm.fr
Benmaamar
Ramla
R
Lê
Bich Thuy
BT
Larmet
Yves
Y
Kalra
Satya P
SP
Marescaux
Christian
C
Depaulis
Antoine
A
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D004195:Disease Models, Animal; D004827:Epilepsy / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D007696:Kindling, Neurologic / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009478:Neuropeptide Y / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D000906:Antibodies; D019208:Brain-Derived Neurotrophic Factor; D009478:Neuropeptide Y