Anticonvulsant and Antiepileptogenic Effects Mediated by Adeno-Associated Virus Vector Neuropeptide Y Expression in the Rat Hippocampus

Cristina Richichi, En Ju D Lin, Daniela Stefanin, Daniele Colella, Teresa Ravizza, Giuliano Grignaschi, Pietro Veglianese, Günther Sperk, Matthew J. During, Annamaria Vezzani

Research output: Contribution to journalArticle

Abstract

Neuropeptide Y (NPY) inhibits seizures in experimental models and reduces excitability in human epileptic tissue. We studied the effect of long-lasting NPY overexpression in the rat hippocampus with local application of recombinant adeno-associated viral (AAV) vectors on acute kainate seizures and kindling epileptogenesis. Transgene expression was significantly increased by 7 d, reached maximal expression by 2 weeks, and persisted for at least 3 months. Serotype 2 AAV vector increased NPY expression in hilar interneurons, whereas the chimeric serotype 1/2 vector caused far more widespread expression, also including mossy fibers, pyramidal cells, and the subiculum. EEG seizures induced by intrahippocampal kainate were reduced by 50-75%, depending on the vector serotype, and seizure onset was markedly delayed. In rats injected with the chimeric serotype 1/2 vector, status epilepticus was abolished, and kindling acquisition was significantly delayed. Thus, targeted NPY gene transfer provides a potential therapeutic principle for the treatment of drug-resistant partial epilepsies.

Original languageEnglish
Pages (from-to)3051-3059
Number of pages9
JournalJournal of Neuroscience
Volume24
Issue number12
DOIs
Publication statusPublished - Mar 24 2004

Keywords

  • Epilepsy
  • Fascia dentata
  • Gene
  • Kainic acid
  • Kindling
  • Seizure

ASJC Scopus subject areas

  • Neuroscience(all)

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