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Differential regulation of mRNAs for neuropeptide Y and its receptor subtypes in widespread areas of the rat limbic system during kindling epileptogenesis

Kopp, Jutta ; Nanobashvili, Avtandil LU ; Kokaia, Zaal LU orcid ; Lindvall, Olle LU and Hökfelt, Tomas (1999) In Molecular Brain Research 72(1). p.17-29
Abstract

Expression of mRNAs for neuropeptide Y (NPY) and its receptor subtypes Y1 (Y1-R), Y2 (Y2-R) and Y5 (Y5-R) was studied in adult rat brain using in situ hybridization after 40 rapidly recurring seizures induced with 5-min interval by hippocampal kindling stimulations. At 2-4 h post-seizure, NPY mRNA levels were markedly elevated in dentate granule cells, CA1 and CA3 pyramidal layers, amygdala and piriform and entorhinal cortices. Gene expression had returned to control level in the dentate granule cell layer at 48 h but remained high in the other areas, reaching baseline at 1 week. Transient decreases of Y1-R mRNA levels were detected at 2-4 h in hippocampal subregions, amygdala, piriform, entorhinal and somatosensory cortices. The Y2-R... (More)

Expression of mRNAs for neuropeptide Y (NPY) and its receptor subtypes Y1 (Y1-R), Y2 (Y2-R) and Y5 (Y5-R) was studied in adult rat brain using in situ hybridization after 40 rapidly recurring seizures induced with 5-min interval by hippocampal kindling stimulations. At 2-4 h post-seizure, NPY mRNA levels were markedly elevated in dentate granule cells, CA1 and CA3 pyramidal layers, amygdala and piriform and entorhinal cortices. Gene expression had returned to control level in the dentate granule cell layer at 48 h but remained high in the other areas, reaching baseline at 1 week. Transient decreases of Y1-R mRNA levels were detected at 2-4 h in hippocampal subregions, amygdala, piriform, entorhinal and somatosensory cortices. The Y2-R mRNA levels were reduced at 2-4 h in the CA3 region and piriform cortex, but exhibited marked increases at 48 h and 1 week post-seizure in the dentate gyrus, amygdala and piriform and entorhinal cortices. At 3 weeks, Y2-R mRNA expression had virtually returned to baseline. Elevated Y5-R mRNA levels were only detected at 2-4 h and confined to dentate granule cell layer and piriform and entorhinal cortices. These results demonstrate a cell- and region-specific, differential regulation of mRNA expression for NPY and Y1-R, Y2-R, and Y5-R in the limbic system following recurring seizures. Because the gene changes were transient, it seems unlikely that the presumed alterations of the corresponding proteins are involved in the maintenance of the epileptic syndrome, which develops up to 4 weeks post-seizure in the present model and is stable thereafter. Our data provide further support for the hypothesis that the changes of NPY and its receptors act to dampen seizure susceptibility, and suggest that the cascade of gene changes is orchestrated to optimize this anticonvulsant effect.

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author
; ; ; and
publishing date
type
Contribution to journal
publication status
published
keywords
Epilepsy, Gene expression, Kindling, Neuropeptide Y, Neuropeptide Y receptor
in
Molecular Brain Research
volume
72
issue
1
pages
13 pages
publisher
Elsevier
external identifiers
  • pmid:10521595
  • scopus:0032826086
ISSN
0169-328X
DOI
10.1016/S0169-328X(99)00191-6
language
English
LU publication?
no
id
4bc629bc-33da-4974-8245-f4ec4db084d8
date added to LUP
2019-09-03 17:02:23
date last changed
2024-01-01 18:44:22
@article{4bc629bc-33da-4974-8245-f4ec4db084d8,
  abstract     = {{<p>Expression of mRNAs for neuropeptide Y (NPY) and its receptor subtypes Y1 (Y1-R), Y2 (Y2-R) and Y5 (Y5-R) was studied in adult rat brain using in situ hybridization after 40 rapidly recurring seizures induced with 5-min interval by hippocampal kindling stimulations. At 2-4 h post-seizure, NPY mRNA levels were markedly elevated in dentate granule cells, CA1 and CA3 pyramidal layers, amygdala and piriform and entorhinal cortices. Gene expression had returned to control level in the dentate granule cell layer at 48 h but remained high in the other areas, reaching baseline at 1 week. Transient decreases of Y1-R mRNA levels were detected at 2-4 h in hippocampal subregions, amygdala, piriform, entorhinal and somatosensory cortices. The Y2-R mRNA levels were reduced at 2-4 h in the CA3 region and piriform cortex, but exhibited marked increases at 48 h and 1 week post-seizure in the dentate gyrus, amygdala and piriform and entorhinal cortices. At 3 weeks, Y2-R mRNA expression had virtually returned to baseline. Elevated Y5-R mRNA levels were only detected at 2-4 h and confined to dentate granule cell layer and piriform and entorhinal cortices. These results demonstrate a cell- and region-specific, differential regulation of mRNA expression for NPY and Y1-R, Y2-R, and Y5-R in the limbic system following recurring seizures. Because the gene changes were transient, it seems unlikely that the presumed alterations of the corresponding proteins are involved in the maintenance of the epileptic syndrome, which develops up to 4 weeks post-seizure in the present model and is stable thereafter. Our data provide further support for the hypothesis that the changes of NPY and its receptors act to dampen seizure susceptibility, and suggest that the cascade of gene changes is orchestrated to optimize this anticonvulsant effect.</p>}},
  author       = {{Kopp, Jutta and Nanobashvili, Avtandil and Kokaia, Zaal and Lindvall, Olle and Hökfelt, Tomas}},
  issn         = {{0169-328X}},
  keywords     = {{Epilepsy; Gene expression; Kindling; Neuropeptide Y; Neuropeptide Y receptor}},
  language     = {{eng}},
  month        = {{09}},
  number       = {{1}},
  pages        = {{17--29}},
  publisher    = {{Elsevier}},
  series       = {{Molecular Brain Research}},
  title        = {{Differential regulation of mRNAs for neuropeptide Y and its receptor subtypes in widespread areas of the rat limbic system during kindling epileptogenesis}},
  url          = {{http://dx.doi.org/10.1016/S0169-328X(99)00191-6}},
  doi          = {{10.1016/S0169-328X(99)00191-6}},
  volume       = {{72}},
  year         = {{1999}},
}