1Int. J. Neuropsychopharmacol. 2009 Sep 12: 1111-26
PMID19254430
TitleDevelopmentally regulated and thalamus-selective induction of leiomodin2 gene by a schizophrenomimetic, phencyclidine, in the rat.
AbstractThe onset of schizophrenia and the schizophrenomimetic effects of an N-methyl-D-aspartate (NMDA) receptor antagonist, ketamine, rarely occur during infancy and childhood, suggesting that schizophrenia-related neuron circuits and molecules in the brain might show an age-related response to an NMDA receptor antagonist. By using a DNA microarray technique, we have identified the developmentally regulated PCP-inducible gene leiomodin2 (LMOD2) that encodes a tropomyosin-binding actin-capping protein enriched in the cardiac and skeletal muscles. PCP caused an increase in the thalamic amounts of LMOD2 transcripts at postnatal days (PD) 32 and 50 without affecting them at PD 8, 13, 20 and 24, while the NMDA antagonist failed to produce a significant change in the gene expression in the adult heart. In-situ hybridization analysis revealed that the basal and PCP-induced expression of the LMOD2 gene is almost confined to the lateral and anterior nuclei of the thalamus among the brain regions at PD 50. The PCP-induced up-regulation of LMOD2 mRNAs in the adult thalamus was mimicked totally (also up-regulated) by another NMDA antagonist, dizocilpine, and partly by the indirect dopamine agonist, methamphetamine. Moreover, pretreatment with a D(2)-preferring dopamine receptor antagonist, haloperidol, partially antagonizes the increasing effects of PCP on thalamic LMOD2 gene expression. These findings suggest that LMOD2 might be involved in the pathophysiology of the age-dependent onset of drug-induced schizophrenia-like psychosis and schizophrenia and that the limited thalamic nuclei expressing the LMOD2 gene could compose the neuron circuits that are specifically disturbed in these mental disorders.
SCZ Keywordsschizophrenia