Abstract |
Neuropeptide Y (NPY) is a 36-amino-acid peptide that attenuates seizure activity following direct infusion or adeno-associated virus (AAV)-mediated expression in the central nervous system. However, NPY activates all NPY receptor subtypes, potentially causing unwanted side effects. NPY13-36 is a C-terminal peptide fragment of NPY that primarily activates the NPY Y2 receptor, thought to mediate the antiseizure activity. Therefore, we investigated if recombinant adeno-associated virus-mediated expression and constitutive secretion of NPY or NPY13-36 could alter limbic seizure sensitivity. Rats received bilateral piriform cortex infusions of AAV vectors that express and constitutively secrete full-length NPY (AAV-FIB-NPY) or NPY13-36 (AAV-FIB-NPY13-36). Control rats received no infusion, as we have previously shown that vectors expressing and secreting reporter genes like GFP (AAV-FIB-EGFP), as well as vectors expressing peptides that lack secretion sequences (AAV-GAL) have no effect on seizures. One week later, all animals received kainic acid (10 mg kg(-1), intraperitoneally), and the latencies to wet dog shakes and limbic seizure behaviors were determined. Although both control and vector-treated rats developed wet dog shake behaviors with similar latencies, the latencies to class III and class IV limbic seizures were significantly prolonged in both NPY- and NPY13-36-treated groups. Thus, AAV-mediated expression and constitutive secretion of NPY and NPY13-36 is effective in attenuating limbic seizures, and provides a platform for delivering therapeutic peptide fragments with increased receptor selectivity.
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Authors | S Foti, R P Haberman, R J Samulski, T J McCown |
Journal | Gene therapy
(Gene Ther)
Vol. 14
Issue 21
Pg. 1534-6
(Nov 2007)
ISSN: 0969-7128 [Print] England |
PMID | 17713567
(Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Neuropeptide Y
- Peptide Fragments
- Receptors, Neuropeptide Y
- neuropeptide Y (13-36)
- neuropeptide Y2 receptor
- Kainic Acid
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Topics |
- Animals
- Dependovirus
(genetics)
- Gene Expression
- Genetic Therapy
(methods)
- Genetic Vectors
(administration & dosage, genetics)
- Hippocampus
(metabolism)
- Kainic Acid
- Models, Animal
- Neuropeptide Y
(genetics, metabolism)
- Peptide Fragments
(genetics, metabolism)
- Rats
- Receptors, Neuropeptide Y
(metabolism)
- Seizures
(metabolism, therapy)
- Time Factors
- Transduction, Genetic
(methods)
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