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Neuropeptide Y Y1 Receptor Hippocampal Overexpression Via Viral Vectors Is Associated With Modest Anxiolytic-Like and Proconvulsant Effects in Mice

Olesen, M. V.; Christiansen, S. H.; Gotzsche, C. R.; Nikitidou, Litsa LU ; Kokaia, Merab LU and Woldbye, D. P. D. (2012) In Journal of Neuroscience Research 90(2). p.498-507
Abstract
Neuropeptide Y (NPY) exerts anxiolytic-and antidepressant-like effects in rodents that appear to be mediated via Y1 receptors. Gene therapy using recombinant viral vectors to induce overexpression of NPY in the hippocampus or amygdala has previously been shown to confer anxiolytic-like effect in rodents. The present study explored an alternative and more specific approach: overexpression of Y1 receptors. Using a recombinant adeno-associated viral vector (rAAV) encoding the Y1 gene (rAAV-Y1), we, for the first time, induced overexpression of functional transgene Y1 receptors in the hippocampus of adult mice and tested the animals in anxiety- and depression-like behavior. Hippocampal Y1 receptors have been suggested to mediate... (More)
Neuropeptide Y (NPY) exerts anxiolytic-and antidepressant-like effects in rodents that appear to be mediated via Y1 receptors. Gene therapy using recombinant viral vectors to induce overexpression of NPY in the hippocampus or amygdala has previously been shown to confer anxiolytic-like effect in rodents. The present study explored an alternative and more specific approach: overexpression of Y1 receptors. Using a recombinant adeno-associated viral vector (rAAV) encoding the Y1 gene (rAAV-Y1), we, for the first time, induced overexpression of functional transgene Y1 receptors in the hippocampus of adult mice and tested the animals in anxiety- and depression-like behavior. Hippocampal Y1 receptors have been suggested to mediate seizure-promoting effect, so the effects of rAAV-induced Y1 receptor overexpression were also tested in kainate-induced seizures. Y1 receptor transgene overexpression was found to be associated with modest anxiolytic-like effect in the open field and elevated plus maze tests, but no effect was seen on depression-like behavior using the tail suspension and forced swim tests. However, the rAAV-Y1 vector modestly aggravated kainate-induced seizures. These data indicate that rAAV-induced overexpression of Y1 receptors in the hippocampus could confer anxiolytic-like effect accompanied by a moderate proconvulsant adverse effect. Further studies are clearly needed to determine whether Y1 gene therapy might have a future role in the treatment of anxiety disorders. (C) 2011 Wiley Periodicals, Inc. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
rAAV, neuropeptide Y, Y1 receptor, anxiety, seizures
in
Journal of Neuroscience Research
volume
90
issue
2
pages
498 - 507
publisher
John Wiley & Sons
external identifiers
  • wos:000299072300016
  • scopus:83155181520
ISSN
1097-4547
DOI
10.1002/jnr.22770
language
English
LU publication?
yes
id
a50a7c7a-d5f9-493e-94ac-d96ba1c14c0b (old id 2355129)
date added to LUP
2012-03-01 11:26:15
date last changed
2017-05-28 04:02:02
@article{a50a7c7a-d5f9-493e-94ac-d96ba1c14c0b,
  abstract     = {Neuropeptide Y (NPY) exerts anxiolytic-and antidepressant-like effects in rodents that appear to be mediated via Y1 receptors. Gene therapy using recombinant viral vectors to induce overexpression of NPY in the hippocampus or amygdala has previously been shown to confer anxiolytic-like effect in rodents. The present study explored an alternative and more specific approach: overexpression of Y1 receptors. Using a recombinant adeno-associated viral vector (rAAV) encoding the Y1 gene (rAAV-Y1), we, for the first time, induced overexpression of functional transgene Y1 receptors in the hippocampus of adult mice and tested the animals in anxiety- and depression-like behavior. Hippocampal Y1 receptors have been suggested to mediate seizure-promoting effect, so the effects of rAAV-induced Y1 receptor overexpression were also tested in kainate-induced seizures. Y1 receptor transgene overexpression was found to be associated with modest anxiolytic-like effect in the open field and elevated plus maze tests, but no effect was seen on depression-like behavior using the tail suspension and forced swim tests. However, the rAAV-Y1 vector modestly aggravated kainate-induced seizures. These data indicate that rAAV-induced overexpression of Y1 receptors in the hippocampus could confer anxiolytic-like effect accompanied by a moderate proconvulsant adverse effect. Further studies are clearly needed to determine whether Y1 gene therapy might have a future role in the treatment of anxiety disorders. (C) 2011 Wiley Periodicals, Inc.},
  author       = {Olesen, M. V. and Christiansen, S. H. and Gotzsche, C. R. and Nikitidou, Litsa and Kokaia, Merab and Woldbye, D. P. D.},
  issn         = {1097-4547},
  keyword      = {rAAV,neuropeptide Y,Y1 receptor,anxiety,seizures},
  language     = {eng},
  number       = {2},
  pages        = {498--507},
  publisher    = {John Wiley & Sons},
  series       = {Journal of Neuroscience Research},
  title        = {Neuropeptide Y Y1 Receptor Hippocampal Overexpression Via Viral Vectors Is Associated With Modest Anxiolytic-Like and Proconvulsant Effects in Mice},
  url          = {http://dx.doi.org/10.1002/jnr.22770},
  volume       = {90},
  year         = {2012},
}