Differential regulation of N-methyl-D-aspartate receptor subunit messenger RNAs in kindling-induced epileptogenesis
Pratt, G D ; Kokaia, M LU ; Bengzon, J LU ; Kokaia, Z LU
; Fritschy, J M
; Möhler, H
and Lindvall, O
LU
(1993)
In Neuroscience
57(2).
p.18-307
- Abstract
N-methyl-D-aspartate-receptors are implicated in several neuropathological conditions including epilepsy. As a model of complex partial seizures, rapid hippocampal kindling was chosen to investigate changes in the expression of messenger RNAs encoding the N-methyl-D-aspartate-receptor subunits NR1, NR2A and NR2B both during and in the period immediately following the induction of the kindled state. The study demonstrates a cell-specific, time-dependent modulation of the N-methyl-D-aspartate-receptor subunit messenger RNAs almost entirely restricted to the granule cells of the dentate gyrus. In partially kindled animals (10 stimulations), while the NR1 subunit messenger RNA remained unaltered after a period of 2 h, the NR2A and NR2B... (More)
N-methyl-D-aspartate-receptors are implicated in several neuropathological conditions including epilepsy. As a model of complex partial seizures, rapid hippocampal kindling was chosen to investigate changes in the expression of messenger RNAs encoding the N-methyl-D-aspartate-receptor subunits NR1, NR2A and NR2B both during and in the period immediately following the induction of the kindled state. The study demonstrates a cell-specific, time-dependent modulation of the N-methyl-D-aspartate-receptor subunit messenger RNAs almost entirely restricted to the granule cells of the dentate gyrus. In partially kindled animals (10 stimulations), while the NR1 subunit messenger RNA remained unaltered after a period of 2 h, the NR2A and NR2B subunit messenger RNAs were bilaterally reduced in dentate gyrus granule cells by around 50% below control values. In fully kindled animals (40 stimulations), a progressive reduction in NR1 subunit messenger RNA levels in the dentate gyrus was observed, being maximal after 4 h (-67%). At the same time point, NR2A and NR2B transcript levels were transiently increased by 102% and 46% above control values, respectively. These data point to a differential regulation of N-methyl-D-aspartate-receptor subunit messenger RNAs. No alterations were detected in pyramidal cells. Long-term maintenance of the kindled state was not associated with alterations in N-methyl-D-aspartate-receptor subunit messenger RNAs since control levels of messenger RNA were attained by 12 h and persisted for at least five days. The early changes in messenger RNAs described in this study indicate that the expression of N-methyl-D-aspartate-receptor subunits is under independent regulatory control. This phenomenon may contribute to epileptogenesis and to kindling-associated plasticity by mediating a structural reorganization of N-methyl-D-aspartate-receptors, leading to an altered excitability of dentate gyrus granule cells.
(Less)
- author
- Pratt, G D
; Kokaia, M
LU
; Bengzon, J
LU
; Kokaia, Z
LU
; Fritschy, J M
; Möhler, H
and Lindvall, O
LU
- organization
- publishing date
- 1993-11
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Animals, Autoradiography, Down-Regulation/physiology, Epilepsy/metabolism, Hippocampus/anatomy & histology, In Situ Hybridization, Kindling, Neurologic, Male, Oligonucleotide Probes, RNA, Messenger/biosynthesis, Rats, Rats, Sprague-Dawley, Receptors, N-Methyl-D-Aspartate/metabolism
- in
- Neuroscience
- volume
- 57
- issue
- 2
- pages
- 12 pages
- publisher
- Elsevier
- external identifiers
-
- pmid:8115040
- scopus:0027431068
- ISSN
- 0306-4522
- DOI
- 10.1016/0306-4522(93)90064-M
- language
- English
- LU publication?
- yes
- id
- dccfa3fd-dc30-4e08-8773-fedc664b9f41
- date added to LUP
- 2019-06-25 10:39:18
- date last changed
- 2023-11-19 07:38:58
@article{dccfa3fd-dc30-4e08-8773-fedc664b9f41,
abstract = {{<p>N-methyl-D-aspartate-receptors are implicated in several neuropathological conditions including epilepsy. As a model of complex partial seizures, rapid hippocampal kindling was chosen to investigate changes in the expression of messenger RNAs encoding the N-methyl-D-aspartate-receptor subunits NR1, NR2A and NR2B both during and in the period immediately following the induction of the kindled state. The study demonstrates a cell-specific, time-dependent modulation of the N-methyl-D-aspartate-receptor subunit messenger RNAs almost entirely restricted to the granule cells of the dentate gyrus. In partially kindled animals (10 stimulations), while the NR1 subunit messenger RNA remained unaltered after a period of 2 h, the NR2A and NR2B subunit messenger RNAs were bilaterally reduced in dentate gyrus granule cells by around 50% below control values. In fully kindled animals (40 stimulations), a progressive reduction in NR1 subunit messenger RNA levels in the dentate gyrus was observed, being maximal after 4 h (-67%). At the same time point, NR2A and NR2B transcript levels were transiently increased by 102% and 46% above control values, respectively. These data point to a differential regulation of N-methyl-D-aspartate-receptor subunit messenger RNAs. No alterations were detected in pyramidal cells. Long-term maintenance of the kindled state was not associated with alterations in N-methyl-D-aspartate-receptor subunit messenger RNAs since control levels of messenger RNA were attained by 12 h and persisted for at least five days. The early changes in messenger RNAs described in this study indicate that the expression of N-methyl-D-aspartate-receptor subunits is under independent regulatory control. This phenomenon may contribute to epileptogenesis and to kindling-associated plasticity by mediating a structural reorganization of N-methyl-D-aspartate-receptors, leading to an altered excitability of dentate gyrus granule cells.</p>}},
author = {{Pratt, G D and Kokaia, M and Bengzon, J and Kokaia, Z and Fritschy, J M and Möhler, H and Lindvall, O}},
issn = {{0306-4522}},
keywords = {{Animals; Autoradiography; Down-Regulation/physiology; Epilepsy/metabolism; Hippocampus/anatomy & histology; In Situ Hybridization; Kindling, Neurologic; Male; Oligonucleotide Probes; RNA, Messenger/biosynthesis; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate/metabolism}},
language = {{eng}},
number = {{2}},
pages = {{18--307}},
publisher = {{Elsevier}},
series = {{Neuroscience}},
title = {{Differential regulation of N-methyl-D-aspartate receptor subunit messenger RNAs in kindling-induced epileptogenesis}},
url = {{http://dx.doi.org/10.1016/0306-4522(93)90064-M}},
doi = {{10.1016/0306-4522(93)90064-M}},
volume = {{57}},
year = {{1993}},
}