Source:http://linkedlifedata.com/resource/pubmed/id/17713567
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
21
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pubmed:dateCreated |
2007-10-16
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pubmed:abstractText |
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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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Kainic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Neuropeptide Y,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Neuropeptide Y,
http://linkedlifedata.com/resource/pubmed/chemical/neuropeptide Y (13-36),
http://linkedlifedata.com/resource/pubmed/chemical/neuropeptide Y2 receptor
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0969-7128
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
14
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1534-6
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pubmed:meshHeading |
pubmed-meshheading:17713567-Animals,
pubmed-meshheading:17713567-Dependovirus,
pubmed-meshheading:17713567-Gene Expression,
pubmed-meshheading:17713567-Gene Therapy,
pubmed-meshheading:17713567-Genetic Vectors,
pubmed-meshheading:17713567-Hippocampus,
pubmed-meshheading:17713567-Kainic Acid,
pubmed-meshheading:17713567-Models, Animal,
pubmed-meshheading:17713567-Neuropeptide Y,
pubmed-meshheading:17713567-Peptide Fragments,
pubmed-meshheading:17713567-Rats,
pubmed-meshheading:17713567-Receptors, Neuropeptide Y,
pubmed-meshheading:17713567-Seizures,
pubmed-meshheading:17713567-Time Factors,
pubmed-meshheading:17713567-Transduction, Genetic
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pubmed:year |
2007
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pubmed:articleTitle |
Adeno-associated virus-mediated expression and constitutive secretion of NPY or NPY13-36 suppresses seizure activity in vivo.
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pubmed:affiliation |
Curriculum in Neurobiology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, N.I.H., Extramural
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