PMID- 8231731 OWN - NLM STAT- MEDLINE DCOM- 19931201 LR - 20190825 IS - 0169-328X (Print) IS - 0169-328X (Linking) VI - 19 IP - 4 DP - 1993 Sep TI - Rapid increase of BDNF mRNA levels in cortical neurons following spreading depression: regulation by glutamatergic mechanisms independent of seizure activity. PG - 277-86 AB - 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. FAU - Kokaia, Z AU - Kokaia Z AD - Department of Neurology, University Hospital, Lund, Sweden. FAU - Gido, G AU - Gido G FAU - Ringstedt, T AU - Ringstedt T FAU - Bengzon, J AU - Bengzon J FAU - Kokaia, M AU - Kokaia M FAU - Siesjo, B K AU - Siesjo BK FAU - Persson, H AU - Persson H FAU - Lindvall, O AU - Lindvall O LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Brain Res Mol Brain Res JT - Brain research. Molecular brain research JID - 8908640 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Membrane Proteins) RN - 0 (Nerve Growth Factors) RN - 0 (Nerve Tissue Proteins) RN - 0 (Oligonucleotide Probes) RN - 0 (Pipecolic Acids) RN - 0 (RNA, Messenger) RN - 0 (Receptor, Ciliary Neurotrophic Factor) RN - 0 (Receptors, N-Methyl-D-Aspartate) RN - 4VGJ4A41L2 (selfotel) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) SB - IM MH - Analysis of Variance MH - Animals MH - Base Sequence MH - Brain-Derived Neurotrophic Factor MH - Cerebral Cortex/drug effects/metabolism/*physiology MH - Cortical Spreading Depression/*physiology MH - In Situ Hybridization MH - Male MH - Membrane Potentials MH - Membrane Proteins/biosynthesis MH - Molecular Sequence Data MH - Nerve Growth Factors/*biosynthesis MH - Nerve Tissue Proteins/*biosynthesis MH - Neurons/metabolism/*physiology MH - Oligonucleotide Probes MH - Parietal Lobe/metabolism/physiology MH - Pipecolic Acids/pharmacology MH - Protein-Tyrosine Kinases/biosynthesis MH - Pyramidal Tracts/metabolism/physiology MH - RNA, Messenger/*biosynthesis/metabolism MH - Rats MH - Rats, Wistar MH - Receptor, Ciliary Neurotrophic Factor MH - Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors MH - Seizures/metabolism/*physiopathology EDAT- 1993/09/01 00:00 MHDA- 1993/09/01 00:01 CRDT- 1993/09/01 00:00 PHST- 1993/09/01 00:00 [pubmed] PHST- 1993/09/01 00:01 [medline] PHST- 1993/09/01 00:00 [entrez] AID - 0169-328X(93)90126-A [pii] AID - 10.1016/0169-328x(93)90126-a [doi] PST - ppublish SO - Brain Res Mol Brain Res. 1993 Sep;19(4):277-86. doi: 10.1016/0169-328x(93)90126-a.