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Biphasic differential changes of GABAA receptor subunit mRNA levels in dentate gyrus granule cells following recurrent kindling-induced seizures

Kokaia, Merab LU ; Pratt, Gerard D; Elmer, Eskil LU ; Bengzon, Johan LU ; Fritschy, Jean-Marc; Kokaia, Zaal LU ; Lindvall, Olle LU and Mohler, Hanns (1994) In Brain Research. Molecular Brain Research 23(4). p.323-332
Abstract
GABAA receptor alpha 1, beta 3 and gamma 2 subunit mRNA levels have been measured in hippocampus using in situ hybridization, following 1, 10 and 40 seizures produced by rapid kindling stimulations. Major alterations of gene expression were largely confined to the dentate gyrus. One stimulus-induced seizure reduced gamma 2 mRNA levels in the dentate gyrus by 30%. In contrast, mRNA expression increased for alpha 1 in CA1 and CA3 and for beta 3 in CA1 to around 30% above control values. Ten stimulations reduced beta 3 (by 19%) and gamma 2 (by 37%) mRNA expression in the dentate gyrus. No changes were observed in other hippocampal subregions. Forty kindling-induced seizures led to biphasic alterations of subunit mRNA levels in dentate gyrus... (More)
GABAA receptor alpha 1, beta 3 and gamma 2 subunit mRNA levels have been measured in hippocampus using in situ hybridization, following 1, 10 and 40 seizures produced by rapid kindling stimulations. Major alterations of gene expression were largely confined to the dentate gyrus. One stimulus-induced seizure reduced gamma 2 mRNA levels in the dentate gyrus by 30%. In contrast, mRNA expression increased for alpha 1 in CA1 and CA3 and for beta 3 in CA1 to around 30% above control values. Ten stimulations reduced beta 3 (by 19%) and gamma 2 (by 37%) mRNA expression in the dentate gyrus. No changes were observed in other hippocampal subregions. Forty kindling-induced seizures led to biphasic alterations of subunit mRNA levels in dentate gyrus with only minor changes in CA1-CA3. Up to 4 h after the last seizure mRNA expression for alpha 1 was slightly decreased in dentate gyrus, whereas marked reductions were observed for beta 3 and gamma 2 (by 41% and 48%, respectively). Between 12 and 48 h there were major increases of alpha 1 (by 59%) and gamma 2 (by 35%) mRNA levels but no significant changes of beta 3 mRNA expression. Subunit mRNA levels had returned to control values after 5 days, which argues against a direct involvement of GABAA receptor in kindling-evoked hyperexcitability. The rapid and transient, biphasic changes of GABAA receptor subunits following recurrent seizures could play an important role in stabilizing granule cell excitability, thereby reducing seizure susceptibility. The differential regulation of subunit mRNA levels following seizures suggests a novel mechanism for changing the physiological properties of dentate granule cells through possible GABAA receptor complexes with different subunit composition. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Hippocampus, Kindling, GABAA receptor subunit, In situ hybridization, Dentate gyrus, Epilepsy
in
Brain Research. Molecular Brain Research
volume
23
issue
4
pages
323 - 332
publisher
Elsevier
external identifiers
  • pmid:8090072
  • scopus:0028283491
ISSN
0169-328X
DOI
10.1016/0169-328X(94)90242-9
language
English
LU publication?
yes
id
b02809ec-d3ae-490d-bef6-8c1b6361897a (old id 1108192)
date added to LUP
2008-07-23 15:18:41
date last changed
2017-08-06 04:26:05
@article{b02809ec-d3ae-490d-bef6-8c1b6361897a,
  abstract     = {GABAA receptor alpha 1, beta 3 and gamma 2 subunit mRNA levels have been measured in hippocampus using in situ hybridization, following 1, 10 and 40 seizures produced by rapid kindling stimulations. Major alterations of gene expression were largely confined to the dentate gyrus. One stimulus-induced seizure reduced gamma 2 mRNA levels in the dentate gyrus by 30%. In contrast, mRNA expression increased for alpha 1 in CA1 and CA3 and for beta 3 in CA1 to around 30% above control values. Ten stimulations reduced beta 3 (by 19%) and gamma 2 (by 37%) mRNA expression in the dentate gyrus. No changes were observed in other hippocampal subregions. Forty kindling-induced seizures led to biphasic alterations of subunit mRNA levels in dentate gyrus with only minor changes in CA1-CA3. Up to 4 h after the last seizure mRNA expression for alpha 1 was slightly decreased in dentate gyrus, whereas marked reductions were observed for beta 3 and gamma 2 (by 41% and 48%, respectively). Between 12 and 48 h there were major increases of alpha 1 (by 59%) and gamma 2 (by 35%) mRNA levels but no significant changes of beta 3 mRNA expression. Subunit mRNA levels had returned to control values after 5 days, which argues against a direct involvement of GABAA receptor in kindling-evoked hyperexcitability. The rapid and transient, biphasic changes of GABAA receptor subunits following recurrent seizures could play an important role in stabilizing granule cell excitability, thereby reducing seizure susceptibility. The differential regulation of subunit mRNA levels following seizures suggests a novel mechanism for changing the physiological properties of dentate granule cells through possible GABAA receptor complexes with different subunit composition.},
  author       = {Kokaia, Merab and Pratt, Gerard D and Elmer, Eskil and Bengzon, Johan and Fritschy, Jean-Marc and Kokaia, Zaal and Lindvall, Olle and Mohler, Hanns},
  issn         = {0169-328X},
  keyword      = {Hippocampus,Kindling,GABAA receptor subunit,In situ hybridization,Dentate gyrus,Epilepsy},
  language     = {eng},
  number       = {4},
  pages        = {323--332},
  publisher    = {Elsevier},
  series       = {Brain Research. Molecular Brain Research},
  title        = {Biphasic differential changes of GABAA receptor subunit mRNA levels in dentate gyrus granule cells following recurrent kindling-induced seizures},
  url          = {http://dx.doi.org/10.1016/0169-328X(94)90242-9},
  volume       = {23},
  year         = {1994},
}