HOMOLATERAL CEREBROCORTICAL INCREASE OF IMMEDIATE-EARLY GENE AND NEUROTRANSMITTER MESSENGER-RNAS AFTER MINIMAL CORTICAL LESION - BLOCKADE BY N-METHYL-D-ASPARTATE ANTAGONIST

A small surgical lesion of the parietal cortex induces an increase in the expression of several messenger RNAs varying from 172 to 980% in t he entire homolateral cerebral cortex, as detected by quantitative in situ hybridization histochemistry. The messenger RNAs encoding the imm ediate early genes of the leucine zipper family (c-fos, c-jun, jun-B), the Zinc finger family (zif268), the glucocorticoid receptor family ( NGF1-B) and the interferon family (PC4) are increased within 2h after the lesion and return to normal levels at 6h. The messenger RNAs encod ing cholecystokinin, neuropeptide Y, somatostatin and the synthetizing enzyme of the neurotransmitter GABA, glutamate decarboxylase, are ele vated within one day and return to normal levels after six days. An in traperitoneal injection of the N-methyl-D-aspartate receptor antagonis t dizocilpine maleate, 30 min before surgery, prevented either the ind uction of immediate early gene expression or the increase of neuropept ide and glutamate decarboxylase messenger RNA expression. This study d emonstrates that a minimal cortical lesion induces extensive changes i n gene expression and that the mechanism(s) leading to these changes i nvolves 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.