Differential actions of NPY on seizure modulation via Y1 and Y2 receptors: evidence from receptor knockout mice.
OBJECTIVE
Neuropeptide Y (NPY) has been shown to modulate seizure activities. To provide further understanding of the involvement of two of the most abundantly expressed NPY receptors, Y1 and Y2, we assessed the effect of Y1 and Y2 gene deletion on systemic kainic acid-induced seizures. We also examined the effect of rAAV-mediated hippocampal NPY overexpression on seizure susceptibility in these receptor knockout mice.


METHODS
Recombinant adeno-associated viral vector overexpressing NPY (rAAV-NPY) or an empty vector control (rAAV-Empty) was injected into the hippocampus of adult C57BL/6-129/SvJ wild-type male mice and mice deficient of Y1 or Y2 receptors on the same background. Four weeks after vector injection, mice were subjected to systemic kainic acid-induced seizures, and the seizure behaviors were scored.


RESULTS
The rAAV-mediated hippocampal overexpression of NPY led to a twofold reduction in seizures induced by systemic kainic acid in wild-type mice and Y1 receptor knockout mice but not in mice deficient of Y2 receptors. A differential action by the receptors was observed in the seizure-induced mortality rate, with increased fatality in Y2-/- mice. In addition, although NPY overexpression did not significantly affect the mortality rate in Y2-/- and wild-type mice, it abolished KA-induced mortality in Y1-/-mice.


CONCLUSIONS
This study shows for the first time an altered susceptibility to chemically induced seizures in Y1 and Y2 knockout mice and demonstrates a differential seizure modulation mediated by these receptors via a genetic approach.
Lin
En-Ju Deborah
EJ
Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand. d.lin@garvan.org.au
Young
Deborah
D
Baer
Kristin
K
Herzog
Herbert
H
During
Matthew J
MJ
D000818:Animals; D004274:DNA, Recombinant / Q000235:genetics; D000229:Dependovirus / Q000235:genetics; D005822:Genetic Vectors / Q000235:genetics; D006624:Hippocampus / Q000503:physiopathology*; D007608:Kainic Acid; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009478:Neuropeptide Y / Q000235:genetics* / Q000494:pharmacology / Q000502:physiology*; D017476:Receptors, Neuropeptide Y / Q000187:drug effects / Q000235:genetics* / Q000502:physiology*; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*
D004274:DNA, Recombinant; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; C095889:neuropeptide Y2 receptor; D007608:Kainic Acid