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Brain insults in rats induce increased expression of the BDNF gene through differential use of multiple promoters

Kokaia, Zaal LU ; Metsis, Madis; Kokaia, Merab LU ; Bengzon, Johan LU ; Elmer, Eskil LU ; Smith, Maj-Lis LU ; Timmusk, Tõnis; Siesjö, Bo LU ; Persson, Håkan and Lindvall, Olle LU (1994) In European Journal of Neuroscience 6(4). p.587-596
Abstract
The rat brain-derived neurotrophic factor (BDNF) gene consists of four short 5'-exons linked to separate promoters and one 3'-exon encoding the mature BDNF protein. Using in situ hybridization we demonstrate here that kindling-induced seizures, cerebral ischaemia and insulin-induced hypoglycaemic coma increase BDNF mRNA levels through insult- and region-specific usage of three promoters within the BDNF gene. Both brief (2 min) and longer (10 min) periods of forebrain ischaemia induced significant and major increases only of exon III mRNA in the dentate gyrus. Following hypoglycaemic coma (1 and 30 min), exon III mRNA was markedly elevated in the dentate gyrus and, in addition, exon I mRNA showed a moderate increase. Single and recurrent (n... (More)
The rat brain-derived neurotrophic factor (BDNF) gene consists of four short 5'-exons linked to separate promoters and one 3'-exon encoding the mature BDNF protein. Using in situ hybridization we demonstrate here that kindling-induced seizures, cerebral ischaemia and insulin-induced hypoglycaemic coma increase BDNF mRNA levels through insult- and region-specific usage of three promoters within the BDNF gene. Both brief (2 min) and longer (10 min) periods of forebrain ischaemia induced significant and major increases only of exon III mRNA in the dentate gyrus. Following hypoglycaemic coma (1 and 30 min), exon III mRNA was markedly elevated in the dentate gyrus and, in addition, exon I mRNA showed a moderate increase. Single and recurrent (n = 40) hippocampal seizures significantly increased expression of exon I, II and III mRNAs in the dentate gyrus granule cells. After recurrent seizures, including generalized convulsions, there were also major increases of both exon I and III mRNAs in the CA3 region, amygdala, piriform cortex and neocortex, whereas in the hippocampal CA1 sector marked elevations were detected only for exon III mRNA. The insults had no effect on the level of exon IV mRNA in the brain. The region- and insult-specific pattern of promoter activation might be of importance for the effectiveness of protective responses as well as for the regulation of plastic changes following brain insults. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
brain-derived neurotrophic factor, rat, in situ hybridization, epilepsy, cerebral ischaemia
in
European Journal of Neuroscience
volume
6
issue
4
pages
587 - 596
publisher
Wiley-Blackwell
external identifiers
  • pmid:8025713
  • scopus:0028299713
ISSN
1460-9568
DOI
10.1111/j.1460-9568.1994.tb00303.x
language
English
LU publication?
yes
id
14538737-8bb7-4633-85d9-22557380cc8e (old id 1108200)
date added to LUP
2008-07-23 15:25:25
date last changed
2017-04-09 03:29:11
@article{14538737-8bb7-4633-85d9-22557380cc8e,
  abstract     = {The rat brain-derived neurotrophic factor (BDNF) gene consists of four short 5'-exons linked to separate promoters and one 3'-exon encoding the mature BDNF protein. Using in situ hybridization we demonstrate here that kindling-induced seizures, cerebral ischaemia and insulin-induced hypoglycaemic coma increase BDNF mRNA levels through insult- and region-specific usage of three promoters within the BDNF gene. Both brief (2 min) and longer (10 min) periods of forebrain ischaemia induced significant and major increases only of exon III mRNA in the dentate gyrus. Following hypoglycaemic coma (1 and 30 min), exon III mRNA was markedly elevated in the dentate gyrus and, in addition, exon I mRNA showed a moderate increase. Single and recurrent (n = 40) hippocampal seizures significantly increased expression of exon I, II and III mRNAs in the dentate gyrus granule cells. After recurrent seizures, including generalized convulsions, there were also major increases of both exon I and III mRNAs in the CA3 region, amygdala, piriform cortex and neocortex, whereas in the hippocampal CA1 sector marked elevations were detected only for exon III mRNA. The insults had no effect on the level of exon IV mRNA in the brain. The region- and insult-specific pattern of promoter activation might be of importance for the effectiveness of protective responses as well as for the regulation of plastic changes following brain insults.},
  author       = {Kokaia, Zaal and Metsis, Madis and Kokaia, Merab and Bengzon, Johan and Elmer, Eskil and Smith, Maj-Lis and Timmusk, Tõnis and Siesjö, Bo and Persson, Håkan and Lindvall, Olle},
  issn         = {1460-9568},
  keyword      = {brain-derived neurotrophic factor,rat,in situ hybridization,epilepsy,cerebral ischaemia},
  language     = {eng},
  number       = {4},
  pages        = {587--596},
  publisher    = {Wiley-Blackwell},
  series       = {European Journal of Neuroscience},
  title        = {Brain insults in rats induce increased expression of the BDNF gene through differential use of multiple promoters},
  url          = {http://dx.doi.org/10.1111/j.1460-9568.1994.tb00303.x},
  volume       = {6},
  year         = {1994},
}