title: Differential regulation of mRNAs for nerve growth factor, brain-derived neurotrophic factor, and neurotrophin 3 in the adult rat brain following cerebral ischemia and hypoglycemic coma.
abstract: In situ hybridization was used to study expression of mRNAs for members of the nerve growth factor (NGF) family in the rat brain after 2 and 10 min of forebrain ischemia and 1 and 30 min of insulin-induced hypoglycemic coma. Two hours after the ischemic insults, the level of brain-derived neurotrophic factor (BDNF) mRNA was markedly increased in the granule cells of the dentate gyrus, and at 24 h it was still significantly elevated. NGF mRNA showed a pronounced increase 4 h after 2 min of ischemia but had returned to a control level at 24 h. Both 2 and 10 min of ischemia caused a clear reduction of the level of mRNA for neurotrophin 3 (NT-3) in the dentate granule cells and in regions CA2 and medial CA1 of the hippocampus 2 and 4 h after the insults. The increase of BDNF mRNA could be partially blocked by the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist NBQX but was not influenced by the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801. Both NBQX and MK-801 attenuated the decrease of NT-3 mRNA after ischemia. One and 30 min of hypoglycemic coma also induced marked increases in BDNF and NGF mRNA in dentate granule cells with maximal levels at 2 h. If the changes of mRNA expression lead to alterations in the relative availability of neurotrophic factors, this could influence functional outcome and neuronal necrosis following ischemic and hypoglycemic insults.
authors.affiliation: Department of Neurology, University Hospital, Lund, Sweden.
authors.forename: O
authors.initials: O
authors.lastname: Lindvall
authors.forename: P
authors.initials: P
authors.lastname: Ernfors
authors.forename: J
authors.initials: J
authors.lastname: Bengzon
authors.forename: Z
authors.initials: Z
authors.lastname: Kokaia
authors.forename: M L
authors.initials: ML
authors.lastname: Smith
authors.forename: B K
authors.initials: BK
authors.lastname: Siesjö
authors.forename: H
authors.initials: H
authors.lastname: Persson
mesh_terms: D000818:Animals; D001921:Brain / Q000503:physiopathology*; D019208:Brain-Derived Neurotrophic Factor; D016291:Dizocilpine Maleate / Q000494:pharmacology; D015870:Gene Expression; D006624:Hippocampus / Q000503:physiopathology; D007331:Insulin Coma / Q000503:physiopathology*; D002546:Ischemic Attack, Transient / Q000503:physiopathology*; D008297:Male; D009414:Nerve Growth Factors / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020933:Neurotrophin 3; D009693:Nucleic Acid Hybridization; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D011810:Quinoxalines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D020933:Neurotrophin 3; D016760:Proto-Oncogene Proteins c-fos; D011810:Quinoxalines; D012333:RNA, Messenger; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D016291:Dizocilpine Maleate