Time course, localization and pharmacological modulation of immediate early inducible genes, brain-derived neurotrophic factor and trkB messenger RNAs in the rat brain following photochemical stroke.
A focal, unilateral thrombotic stroke was produced in the rat sensorimotor cortex. The time course of expression and localization of the immediate early inducible genes: c-fos, c-jun, zif268; nerve growth factor, brain-derived neurotrophic factor and the related tyrosine kinase high-affinity receptor (trkB) messenger RNAs were studied by in situ hybridization. The levels of messenger RNAs for c-fos, zif268, brain-derived neurotrophic factor (but not nerve growth factor) and trkB were consistently increased in cortex ipsilaterally to the lesion, while c-jun messenger RNA content was only slightly increased. The brain-derived neurotrophic factor messenger RNA was increased from 2 to 18 h following the stroke, mainly in cells having a normal morphological appearance. The trkB messenger RNA displayed temporal and spatial increases similar to brain-derived neurotrophic factor messenger RNA. The time course and pattern of expression of immediate early inducible gene and trophic factor messenger RNAs did not clearly support a causal relationship between these two families of factors. The observed messenger RNA increases were greatly attenuated by the non-competitive N-methyl-D-aspartate-sensitive glutamate receptor antagonist (+)-5-methyl-10,11-dihydroxy-5H-dibenzo(a,d)cyclohepten-5,10-imine , but substantially unaffected by the non-N-methyl-D-aspartate receptor antagonist 2,3-dihydroxy-6-nitrosulphanoylbenzoquinoxaline. The results suggest a major contribution of N-methyl-D-aspartate-sensitive glutamate receptor activation to the transcriptionally directed events subsequent to stroke. Future studies should clarify the contribution of these processes to either the progression of neuronal degeneration or the establishment of protective compensatory responses.
Comelli
M C
MC
Fidia Research Laboratories, Abano Terme, Italy.
Guidolin
D
D
Seren
M S
MS
Zanoni
R
R
Canella
R
R
Rubini
R
R
Manev
H
H
D000818:Animals; D001921:Brain / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor; D002561:Cerebrovascular Disorders / Q000139:chemically induced / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000032:analysis / Q000096:biosynthesis; D016291:Dizocilpine Maleate / Q000494:pharmacology; D051766:Early Growth Response Protein 1; D015870:Gene Expression / Q000187:drug effects; D016762:Genes, fos; D016758:Genes, jun; D017874:Immediate-Early Proteins; D017403:In Situ Hybridization; D007700:Kinetics; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000096:biosynthesis*; D009414:Nerve Growth Factors / Q000096:biosynthesis*; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000096:biosynthesis*; D010777:Photochemistry; D011505:Protein-Tyrosine Kinases / Q000032:analysis / Q000096:biosynthesis*; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000096:biosynthesis*; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis / Q000096:biosynthesis; D016755:Proto-Oncogene Proteins c-jun / Q000032:analysis / Q000096:biosynthesis; D011519:Proto-Oncogenes; D011810:Quinoxalines / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020801:Receptor, Ciliary Neurotrophic Factor; D012395:Rose Bengal; D013997:Time Factors; D014157:Transcription Factors / Q000032:analysis / Q000096:biosynthesis
D019208:Brain-Derived Neurotrophic Factor; D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D017874:Immediate-Early Proteins; D008565:Membrane Proteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D011810:Quinoxalines; D012333:RNA, Messenger; D020801:Receptor, Ciliary Neurotrophic Factor; D014157:Transcription Factors; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D012395:Rose Bengal; D016291:Dizocilpine Maleate; D011505:Protein-Tyrosine Kinases