Seizure susceptibility and epileptogenesis are decreased in transgenic rats overexpressing neuropeptide Y.

Abstract

Functional studies in epileptic tissue indicate that neuropeptide Y and some of its peptide analogs potently inhibit seizure activity. We investigated seizure susceptibility in transgenic rats overexpressing the rat neuropeptide Y gene under the control of its natural promoter. Seizures were induced in adult transgenic male rats and their wild-type littermates by i.c.v. injection of 0.3 microg kainic acid or by electrical kindling of the dorsal hippocampus. Transgenic rats showed a significant reduction in the number and duration of electroencephalographic seizures induced by kainate by 30% and 55% respectively (P<0.05 and 0.01). Transgenic rats were also less susceptible to epileptogenesis than wild-type littermates as demonstrated by a 65% increase in the number of electrical stimuli required to induce stage 5 seizures (P<0.01). This phenotype was associated with a strong and specific expression of neuropeptide Y mRNA in area CA1, a brain area involved in the seizure network. We conclude that endogenous neuropeptide Y overexpression in the rat hippocampus is associated with inhibition of seizures and epileptogenesis suggesting that this system may be a valuable target for developing novel antiepileptic treatments.

• Authors: A Vezzani, M Michalkiewicz, T Michalkiewicz, D Moneta, T Ravizza, C Richichi, M Aliprandi, F Mulé, L Pirona, M Gobbi, C Schwarzer, G Sperk
• Journal: Neuroscience (Neuroscience) Vol. 110 Issue 2 Pg. 237-43 ( 2002) ISSN: 0306-4522 [Print] United States
• PMID: 11958866 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Excitatory Amino Acid Agonists
• Neuropeptide Y
• RNA, Messenger

Topics

• Animals
• Animals, Genetically Modified
• Electric Stimulation
• Electroencephalography (drug effects)
• Epilepsy (chemically induced, genetics, physiopathology)
• Epilepsy, Temporal Lobe (metabolism, physiopathology)
• Excitatory Amino Acid Agonists (pharmacology)
• Gene Expression Regulation (physiology)
• Genetic Predisposition to Disease (genetics)
• Hippocampus (drug effects, metabolism, physiopathology)
• Kindling, Neurologic (drug effects, genetics)
• Male
• Neurons (drug effects, metabolism)
• Neuropeptide Y (genetics)
• Promoter Regions, Genetic (genetics)
• RNA, Messenger (metabolism)
• Rats
• Rats, Sprague-Dawley
• Up-Regulation (genetics)