Linked Life Data

17713567

Source:http://linkedlifedata.com/resource/pubmed/id/17713567

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pubmed-article:17713567pubmed:abstractTextNeuropeptide 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.lld:pubmed
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pubmed-article:17713567pubmed:year2007lld:pubmed
pubmed-article:17713567pubmed:articleTitleAdeno-associated virus-mediated expression and constitutive secretion of NPY or NPY13-36 suppresses seizure activity in vivo.lld:pubmed
pubmed-article:17713567pubmed:affiliationCurriculum in Neurobiology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.lld:pubmed
pubmed-article:17713567pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:17713567pubmed:publicationTypeComparative Studylld:pubmed
pubmed-article:17713567pubmed:publicationTypeResearch Support, N.I.H., Extramurallld:pubmed
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