Differential changes in messenger RNA expressions and binding sites of neuropeptide Y Y1, Y2 and Y5 receptors in the hippocampus of an epileptic mutant rat: Noda epileptic rat.
The anti-convulsive effects of neuropeptide Y have been suggested in several animal models of epilepsy. We have found the sustained increase of neuropeptide Y contents and the seizure-induced elevation of hippocampal messenger RNA in a novel spontaneous epileptic mutant rat: Noda epileptic rat. In the present study, we investigated the change of neuropeptide Y Y1 and Y2 receptor messenger RNA expressions and binding sites in the hippocampus following a spontaneous generalized tonic-clonic seizure of Noda epileptic rat. Furthermore, the binding sites of a more recently isolated receptor subtype, neuropeptide Y Y5 receptors, were also evaluated by receptor autoradiography. A marked elevation of neuropeptide Y immunoreactivity in the mossy fiber, and Y2-receptor up-regulation in the dentate gyrus were observed in the hippocampus of Noda epileptic rat, which coincided with the previous results of the other epileptic models. In contrast, Y1-receptor down-regulation was not found after a spontaneous seizure of Noda epileptic rat while this occurs in kindling and after kainic acid-induced seizures. [125I][Leu31, Pro34]peptide YY/BIBP 3226-insensitive (Y5 receptor) binding sites in CA1 stratum radiatum were significantly decreased following a spontaneous seizure of Noda epileptic rat. The present results suggest that a spontaneous seizure of Noda epileptic rat induces significant changes in neuropeptide Y-mediated transmission in the hippocampus via Y2 and Y5 receptors, but not Y1 receptors. Therefore, specific subset of neuropeptide Y receptor subtypes might be involved in the epileptogenesis of Noda epileptic rat.
Jinde
S
S
Department of Neuropsychiatry, Graduate School of Medicine, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113-8655, Tokyo, Japan. jind-tky@umin.ac.jp
Masui
A
A
Morinobu
S
S
Noda
A
A
Kato
N
N
D000818:Animals; D018891:Dentate Gyrus / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D004827:Epilepsy / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism* / Q000503:physiopathology; D007150:Immunohistochemistry; D007457:Iodine Radioisotopes; D008297:Male; D019599:Mossy Fibers, Hippocampal / Q000378:metabolism / Q000503:physiopathology / Q000648:ultrastructure; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009478:Neuropeptide Y / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D017966:Pyramidal Cells / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011922:Rats, Mutant Strains; D017476:Receptors, Neuropeptide Y / Q000235:genetics*
D007457:Iodine Radioisotopes; D009478:Neuropeptide Y; D010446:Peptide Fragments; D012333:RNA, Messenger; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; C095889:neuropeptide Y2 receptor; C100568:neuropeptide Y5 receptor