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 signiicantly 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 a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist NBQX but was not influenced by the N-methyl-I-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.

Inhibition of GABAASynaptic Responses by Brain-Derived Neurotrophic Factor (BDNF) in Rat Hippocampus

“…The present study using BDNF, a specific ligand for TrkB, indicates that TrkB participates in the modulation of GABA A receptor function, although TrkC also may regulate it. However, in contrast to BDNF expression, NT-3 expression level is downregulated in the adult brain by neuronal activity (Lindvall et al, 1992;Rocamora et al, 1992Rocamora et al, , 1994Bengzon et al, 1993) (but also see Patterson et al, 1992). In this respect, it is difficult to regard NT-3 as a signal that is secreted activity dependently, which triggers neural plasticity.…”

Suppression of ischemia‐induced fos expression and AP‐1 activity by an antisense oligodeoxynucleotide to c‐fos mRNA

“…Recent observations of altered gene expression in ischemic brain using animal stroke models have opened new avenues for exploration of the biochemical cascades after stroke [1][2][3][4][5][6][7][8][9][10][11]. These postischemic events include an increase in extracellular excitatory amino acid neurotransmitters such as glutamate.…”

“…A number of genes that bear neurotrophic properties may be regulated by transcription regulator AP-1. These genes, such as heat shock protein [1,4,[19][20][21][22], amyloid [23], neurotrophins [7], and protein tyrosine kinase receptor trkB [24], have been shown to be induced following cerebral ischemia. The causal relationship between the Fos/Jun-AP-1 cascade and the subsequent expression of the late effector genes, however, has not been studied.…”

Actions of Brain-Derived Neurotrophic Factor in Slices from Rats with Spontaneous Seizures and Mossy Fiber Sprouting in the Dentate Gyrus

“…If endogenous BDN F reaches concentrations similar to the concentrations of bath-applied BDNF that were used in the above experiments, the actions of endogenous and bath-applied BDN F could be similar. Even if normal concentrations of BDN F are low, endogenous BDNF still might have f unctional effects under certain conditions, because BDNF message, protein, and trkB expression increase after various events (such as after neuronal activity, sensory stimulation, learning, long-term potentiation, stress, injury, and seizures) (Ballarín et al, 1991;Z afra et al, 1991;Falkenberg et al, 1992a,b;Lindefors et al, 1992;Lindvall et al, 1992Lindvall et al, , 1994Patterson et al, 1992;Beck et al, 1993;C astrén et al, 1993;Cosi et al, 1993;Dragunow et al, 1993;Humpel et al, 1993;Lapchak et al, 1993;Merlio et al, 1993;Springer et al, 1994;Lauterborn et al, 1995;Nibuya et al, 1995;Arai et al, 1996;Bramham et al, 1996;Mudò et al, 1996;Schmidt-Kastner et al, 1996;Kawahara et al, 1997;Vaidya et al, 1997;Bova et al, 1998;Oliff et al, 1998).…”