title: Homolateral cerebrocortical increase of immediate early gene and neurotransmitter messenger RNAs after minimal cortical lesion: blockade by N-methyl-D-aspartate antagonist.
abstract: A small surgical lesion of the parietal cortex induces an increase in the expression of several messenger RNAs varying from 172 to 980% in the entire homolateral cerebral cortex, as detected by quantitative in situ hybridization histochemistry. The messenger RNAs encoding the immediate early genes of the leucine zipper family (c-fos, c-jun, jun-B), the Zinc finger family (zif268), the glucocorticoid receptor family (NGFI-B) and the interferon family (PC4) are increased within 2 h after the lesion and return to normal levels at 6 h. The messenger RNAs encoding cholecystokinin, neuropeptide Y, somatostatin and the synthetizing enzyme of the neurotransmitter GABA, glutamate decarboxylase, are elevated within one day and return to normal levels after six days. An intraperitoneal injection of the N-methyl-D-aspartate receptor antagonist dizocilpine maleate, 30 min before surgery, prevented either the induction of immediate early gene expression or the increase of neuropeptide and glutamate decarboxylase messenger RNA expression. This study demonstrates that a minimal cortical lesion induces extensive changes in gene expression and that the mechanism(s) leading to these changes involves the action of glutamate at the N-methyl-D-aspartate receptor. These modifications may be of importance in explaining diffuse changes not related to neuronal circuitry in several conditions.
authors.affiliation: Brain Research Unit, Faculty of Medicine, Université Libre de Bruxelles, Belgium.
authors.forename: O
authors.initials: O
authors.lastname: Jacobs
authors.forename: L
authors.initials: L
authors.lastname: Van Bree
authors.forename: P
authors.initials: P
authors.lastname: Mailleux
authors.forename: F
authors.initials: F
authors.lastname: Zhang
authors.forename: S N
authors.initials: SN
authors.lastname: Schiffmann
authors.forename: P
authors.initials: P
authors.lastname: Halleux
authors.forename: N
authors.initials: N
authors.lastname: Albala
authors.forename: J J
authors.initials: JJ
authors.lastname: Vanderhaeghen
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D002544:Cerebral Infarction / Q000503:physiopathology; D002766:Cholecystokinin / Q000096:biosynthesis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D051766:Early Growth Response Protein 1; D005260:Female; D005786:Gene Expression Regulation; D017781:Genes, Immediate-Early; D016762:Genes, fos; D016758:Genes, jun; D005968:Glutamate Decarboxylase / Q000096:biosynthesis / Q000235:genetics; D005971:Glutamates / Q000502:physiology*; D018698:Glutamic Acid; D017874:Immediate-Early Proteins; D016350:Leucine Zippers / Q000235:genetics; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009478:Neuropeptide Y / Q000096:biosynthesis / Q000235:genetics; D018377:Neurotransmitter Agents / Q000096:biosynthesis*; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D010296:Parietal Lobe / Q000293:injuries*; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D013004:Somatostatin / Q000096:biosynthesis / Q000235:genetics; D013997:Time Factors; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D016335:Zinc Fingers / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D005971:Glutamates; C490045:IFRD1 protein, human; C084979:Ifrd1 protein, rat; D017874:Immediate-Early Proteins; D008565:Membrane Proteins; C539821:NR4A1 protein, human; D009419:Nerve Tissue Proteins; D009478:Neuropeptide Y; D018377:Neurotransmitter Agents; C539820:Nr4a1 protein, rat; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D014157:Transcription Factors; D018698:Glutamic Acid; D013004:Somatostatin; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D002766:Cholecystokinin; D005968:Glutamate Decarboxylase