Skip Navigation


Brain Advance Access originally published online on May 13, 2008
Brain 2008 131(6):1506-1515; doi:10.1093/brain/awn079
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Supplementary Data
Right arrow All Versions of this Article:
131/6/1506    most recent
awn079v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Noè, F.
Right arrow Articles by Vezzani, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Noè, F.
Right arrow Articles by Vezzani, A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author (2008). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

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

Francesco Noè1, Allan-Hermann Pool2, Jari Nissinen2, Marco Gobbi3, Ross Bland4, Massimo Rizzi1, Claudia Balducci1, Francesco Ferraguti5, Gunther Sperk5, Matthew J. During6, Asla Pitkänen2,7 and Annamaria Vezzani1

1Department of Neuroscience, Mario Negri Institute for Pharmacological Research, Milano, Italy, 2Epilepsy Research Lab, A.I. Virtanen Institute for Molecular Science, University of Kuopio, Kuopio, Finland 3Department of Biochemistry, Mario Negri Institute for Pharmacological Research, Milano, Italy, 4Neurologix, Inc., Columbus, Ohio, USA, 5Department of Pharmacology, Medical University, Innsbruck, Austria, 6Human Cancer Genetics Programme, The Ohio State University, Columbus, Ohio, USA and 7Department of Neurology, Kuopio University Hospital, Kuopio, Finland

Correspondence to: Annamaria Vezzani, PhD, Lab Exp Neurol, Department of Neuroscience, Mario Negri Inst for Pharmacol Res, Via G. la Masa 19, 20156 Milano, Italy E-mail: vezzani{at}marionegri.it

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.

Key Words: adeno-associated viral vectors; anti-convulsant; EEG; hippocampus; neuropeptides

Abbreviations: AEDs, anti-epileptic drugs; CMV, cytomegalovirus; NPY, neuropeptide Y; rAAV, recombinant adeno-associated viral.

Received November 22, 2007. Revised March 25, 2008. Accepted April 2, 2008.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.