Neuropeptide Y gene therapy decreases chronic spontaneous seizures in a rat model of temporal lobe epilepsy

Francesco Noè, Allan Hermann Pool, Jari Nissinen, Marco Gobbi, Ross Bland, Massimo Rizzi, Claudia Balducci, Francesco Ferraguti, Gunther Sperk, Matthew J. During, Asla Pitkänen, Annamaria Vezzani

Research output: Contribution to journalArticlepeer-review

Abstract

Temporal lobe epilepsy remains amongst the most common and drug refractory of neurological disorders. Gene therapy may provide a realistic therapeutic approach alternative to surgery for intractable focal epilepsies. To test this hypothesis, we applied here a gene therapy approach, using a recombinant adeno-associated viral (rAAV) vector expressing the human neuropeptide Y (NPY) gene, to a progressive and spontaneous seizure model of temporal lobe epilepsy induced by electrical stimulation of the temporal pole of the hippocampus, which replicates many features of the human condition. rAAV-NPY or a control vector lacking the expression cassette (rAAV-Empty) was delivered into the epileptic rat hippocampi at an early progressive stage of the disease. Chronic epileptic rats were video-EEG monitored to establish pre-injection baseline recordings of spontaneous seizures and the effect of rAAV-NPY versus rAAV-Empty vector injection. Both non-injected stimulated controls and rAAV-empty injected rats showed a similar progressive increase of spontaneous seizure frequency consistent with epileptogenesis. The delivery of rAAV-NPY in epileptic rat brain leads to a remarkable decrease in the progression of seizures as compared to both control groups and this effect was correlated with the NPY over-expression in the hippocampus. Moreover, spontaneous seizure frequency was significantly reduced in 40% of treated animals as compared to their pre-injection baseline. Our data show that this gene therapy strategy decreases spontaneous seizures and suppresses their progression in chronic epileptic rats, thus representing a promising new therapeutic strategy.

Original languageEnglish
Pages (from-to)1506-1515
Number of pages10
JournalBrain
Volume131
Issue number6
DOIs
Publication statusPublished - Jun 2008

Keywords

  • Adeno-associated viral vectors
  • Anti-convulsant
  • EEG
  • Hippocampus
  • Neuropeptides

ASJC Scopus subject areas

  • Neuroscience(all)

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