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Rapid increase of BDNF mRNA levels in cortical neurons following spreading depression : regulation by glutamatergic mechanisms independent of seizure activity

Kokaia, Z LU orcid ; Gidö, G LU ; Ringstedt, T ; Bengzon, J LU ; Kokaia, M LU ; Siesjö, B K LU ; Persson, H and Lindvall, O LU (1993) In Brain Research. Molecular Brain Research 19(4). p.277-286
Abstract

Levels of mRNA for nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and the tyrosine kinase receptors trkB and trkC have been studied using in situ hybridization in the rat brain after topical application of KCl to the cortical surface (which induces spreading depression). Repeated episodes of spreading depression during 2 h caused a rapid and marked increase of BDNF mRNA levels in deep and, in particular, superficial cortical layers of the ipsilateral hemisphere (to 213 and 417% of control, respectively). Maximal levels were reached within 2 h after the cessation of spreading depression and at 24 h BDNF mRNA expression had returned to control values. Levels of BDNF mRNA were unaffected in the... (More)

Levels of mRNA for nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and the tyrosine kinase receptors trkB and trkC have been studied using in situ hybridization in the rat brain after topical application of KCl to the cortical surface (which induces spreading depression). Repeated episodes of spreading depression during 2 h caused a rapid and marked increase of BDNF mRNA levels in deep and, in particular, superficial cortical layers of the ipsilateral hemisphere (to 213 and 417% of control, respectively). Maximal levels were reached within 2 h after the cessation of spreading depression and at 24 h BDNF mRNA expression had returned to control values. Levels of BDNF mRNA were unaffected in the hippocampus, in areas outside the cerebral cortex and in the contralateral hemisphere. Furthermore, no change of the expression of mRNA for NGF, NT-3, trkC or the full length trkB receptor was detected at any time point. However, at 2 h after spreading depression there was an increased level (150% of control) in superficial cortical layers of mRNA hybridizing to an oligonucleotide probe detecting both truncated receptors lacking the tyrosine kinase domain and full length trkB receptors. Also one single episode of spreading depression gave rise to a significant increase of cortical BDNF mRNA levels (to 207% of control), which was attenuated (by 61%) after administration of the competitive NMDA receptor antagonist CGS 19755. The results provide evidence that mild brain insults associated with glutamate release and elevated intracellular calcium, such as spreading depression, also in the absence of seizure activity can lead to activation of the BDNF gene in cortical neurons.

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author
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publishing date
type
Contribution to journal
publication status
published
subject
keywords
Analysis of Variance, Animals, Base Sequence, Brain-Derived Neurotrophic Factor, Cerebral Cortex/drug effects, Cortical Spreading Depression/physiology, In Situ Hybridization, Male, Membrane Potentials, Membrane Proteins/biosynthesis, Molecular Sequence Data, Nerve Growth Factors/biosynthesis, Nerve Tissue Proteins/biosynthesis, Neurons/metabolism, Oligonucleotide Probes, Parietal Lobe/metabolism, Pipecolic Acids/pharmacology, Protein-Tyrosine Kinases/biosynthesis, Pyramidal Tracts/metabolism, RNA, Messenger/biosynthesis, Rats, Rats, Wistar, Receptor, Ciliary Neurotrophic Factor, Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors, Seizures/metabolism
in
Brain Research. Molecular Brain Research
volume
19
issue
4
pages
277 - 286
publisher
Elsevier
external identifiers
  • pmid:8231731
  • scopus:0027203903
ISSN
0169-328X
DOI
10.1016/0169-328X(93)90126-A
language
English
LU publication?
no
id
25926ba6-adf3-4896-9a3e-fd32c00fb165
date added to LUP
2019-06-25 10:40:57
date last changed
2024-01-16 05:31:09
@article{25926ba6-adf3-4896-9a3e-fd32c00fb165,
  abstract     = {{<p>Levels of mRNA for nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and the tyrosine kinase receptors trkB and trkC have been studied using in situ hybridization in the rat brain after topical application of KCl to the cortical surface (which induces spreading depression). Repeated episodes of spreading depression during 2 h caused a rapid and marked increase of BDNF mRNA levels in deep and, in particular, superficial cortical layers of the ipsilateral hemisphere (to 213 and 417% of control, respectively). Maximal levels were reached within 2 h after the cessation of spreading depression and at 24 h BDNF mRNA expression had returned to control values. Levels of BDNF mRNA were unaffected in the hippocampus, in areas outside the cerebral cortex and in the contralateral hemisphere. Furthermore, no change of the expression of mRNA for NGF, NT-3, trkC or the full length trkB receptor was detected at any time point. However, at 2 h after spreading depression there was an increased level (150% of control) in superficial cortical layers of mRNA hybridizing to an oligonucleotide probe detecting both truncated receptors lacking the tyrosine kinase domain and full length trkB receptors. Also one single episode of spreading depression gave rise to a significant increase of cortical BDNF mRNA levels (to 207% of control), which was attenuated (by 61%) after administration of the competitive NMDA receptor antagonist CGS 19755. The results provide evidence that mild brain insults associated with glutamate release and elevated intracellular calcium, such as spreading depression, also in the absence of seizure activity can lead to activation of the BDNF gene in cortical neurons.</p>}},
  author       = {{Kokaia, Z and Gidö, G and Ringstedt, T and Bengzon, J and Kokaia, M and Siesjö, B K and Persson, H and Lindvall, O}},
  issn         = {{0169-328X}},
  keywords     = {{Analysis of Variance; Animals; Base Sequence; Brain-Derived Neurotrophic Factor; Cerebral Cortex/drug effects; Cortical Spreading Depression/physiology; In Situ Hybridization; Male; Membrane Potentials; Membrane Proteins/biosynthesis; Molecular Sequence Data; Nerve Growth Factors/biosynthesis; Nerve Tissue Proteins/biosynthesis; Neurons/metabolism; Oligonucleotide Probes; Parietal Lobe/metabolism; Pipecolic Acids/pharmacology; Protein-Tyrosine Kinases/biosynthesis; Pyramidal Tracts/metabolism; RNA, Messenger/biosynthesis; Rats; Rats, Wistar; Receptor, Ciliary Neurotrophic Factor; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors; Seizures/metabolism}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{277--286}},
  publisher    = {{Elsevier}},
  series       = {{Brain Research. Molecular Brain Research}},
  title        = {{Rapid increase of BDNF mRNA levels in cortical neurons following spreading depression : regulation by glutamatergic mechanisms independent of seizure activity}},
  url          = {{http://dx.doi.org/10.1016/0169-328X(93)90126-A}},
  doi          = {{10.1016/0169-328X(93)90126-A}},
  volume       = {{19}},
  year         = {{1993}},
}