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NPY gene transfer in the hippocampus attenuates synaptic plasticity and learning.

Toft Sörensen, Andreas LU ; Kanter Schlifke, Irene LU ; Carli, Mirjana; Balducci, Claudia; Noe, Francesco; During, Matthew J; Vezzani, Annamaria and Kokaia, Merab LU (2008) In Hippocampus 18(6). p.564-574
Abstract
Recombinant adeno-associated viral (rAAV) vector-induced neuropeptide Y (NPY) overexpression in the hippocampus exerts powerful antiepileptic and antiepileptogenic effects in rats. Such gene therapy approach could be a valuable alternative for developing new antiepileptic treatment strategies. Future clinical progress, however, requires more detailed evaluation of possible side effects of this treatment. Until now it has been unknown whether rAAV vector-based NPY overexpression in the hippocampus alters normal synaptic transmission and plasticity, which could disturb learning and memory processing. Here we show, by electrophysiological recordings in CA1 of the hippocampal formation of rats, that hippocampal NPY gene transfer into the... (More)
Recombinant adeno-associated viral (rAAV) vector-induced neuropeptide Y (NPY) overexpression in the hippocampus exerts powerful antiepileptic and antiepileptogenic effects in rats. Such gene therapy approach could be a valuable alternative for developing new antiepileptic treatment strategies. Future clinical progress, however, requires more detailed evaluation of possible side effects of this treatment. Until now it has been unknown whether rAAV vector-based NPY overexpression in the hippocampus alters normal synaptic transmission and plasticity, which could disturb learning and memory processing. Here we show, by electrophysiological recordings in CA1 of the hippocampal formation of rats, that hippocampal NPY gene transfer into the intact brain does not affect basal synaptic transmission, but slightly alters short-term synaptic plasticity, most likely via NPY Y2 receptor-mediated mechanisms. In addition, transgene NPY seems to be released during high frequency neuronal activity, leading to decreased glutamate release in excitatory synapses. Importantly, memory consolidation appears to be affected by the treatment. We found that long-term potentiation (LTP) in the CA1 area is partially impaired and animals have a slower rate of hippocampal-based spatial discrimination learning. These data provide the first evidence that rAAV-based gene therapy using NPY exerts relative limited effect on synaptic plasticity and learning in the hippocampus, and therefore this approach could be considered as a viable alternative for epilepsy treatment. (c) 2008 Wiley-Liss, Inc. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Hippocampus
volume
18
issue
6
pages
564 - 574
publisher
John Wiley & Sons
external identifiers
  • pmid:18306304
  • wos:000256576100005
  • scopus:45149086454
ISSN
1050-9631
DOI
10.1002/hipo.20415
language
English
LU publication?
yes
id
06d44227-c1aa-4dd0-834d-4b3038c9b433 (old id 1041427)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18306304?dopt=Abstract
http://onlinelibrary.wiley.com/doi/10.1002/hipo.20415/abstract
date added to LUP
2008-03-06 13:55:02
date last changed
2017-09-10 03:52:01
@article{06d44227-c1aa-4dd0-834d-4b3038c9b433,
  abstract     = {Recombinant adeno-associated viral (rAAV) vector-induced neuropeptide Y (NPY) overexpression in the hippocampus exerts powerful antiepileptic and antiepileptogenic effects in rats. Such gene therapy approach could be a valuable alternative for developing new antiepileptic treatment strategies. Future clinical progress, however, requires more detailed evaluation of possible side effects of this treatment. Until now it has been unknown whether rAAV vector-based NPY overexpression in the hippocampus alters normal synaptic transmission and plasticity, which could disturb learning and memory processing. Here we show, by electrophysiological recordings in CA1 of the hippocampal formation of rats, that hippocampal NPY gene transfer into the intact brain does not affect basal synaptic transmission, but slightly alters short-term synaptic plasticity, most likely via NPY Y2 receptor-mediated mechanisms. In addition, transgene NPY seems to be released during high frequency neuronal activity, leading to decreased glutamate release in excitatory synapses. Importantly, memory consolidation appears to be affected by the treatment. We found that long-term potentiation (LTP) in the CA1 area is partially impaired and animals have a slower rate of hippocampal-based spatial discrimination learning. These data provide the first evidence that rAAV-based gene therapy using NPY exerts relative limited effect on synaptic plasticity and learning in the hippocampus, and therefore this approach could be considered as a viable alternative for epilepsy treatment. (c) 2008 Wiley-Liss, Inc.},
  author       = {Toft Sörensen, Andreas and Kanter Schlifke, Irene and Carli, Mirjana and Balducci, Claudia and Noe, Francesco and During, Matthew J and Vezzani, Annamaria and Kokaia, Merab},
  issn         = {1050-9631},
  language     = {eng},
  number       = {6},
  pages        = {564--574},
  publisher    = {John Wiley & Sons},
  series       = {Hippocampus},
  title        = {NPY gene transfer in the hippocampus attenuates synaptic plasticity and learning.},
  url          = {http://dx.doi.org/10.1002/hipo.20415},
  volume       = {18},
  year         = {2008},
}