Gene expression profiles of nucleus accumbens, prefrontal cortex and hippocampus in an animal model of schizophrenia: proposed candidate genes.

Introduction: It has been suggested that schizophrenia may be induced by “accidents” or injuries that occur during early brain development and result in a reduction of the neural connections in different regions. In this study, we evaluated differences in the expression of brain genes using a recognized experimental prototype of schizophrenia: the animal model of ventral hippocampal lesion in neonate rats (VHLN) compared to control animals.

Methods: Using microarray technology, we obtained gene expression profiles of three brain areas (nucleus accumbens, prefrontal cortex and hippocampus) of juvenile (45 days) and adult (90 days) Wistar male rats that underwent either VHLN or sham VHLN.

Results: Based on three criteria: 1) expression in more than one brain area, 2) participation in cellular pathways relevant to the central nervous system (CNS), 3) Z-score values >2 (overexpression) and <-2 (underexpression), we found overexpression of the ppp3cb, dctn1, jag1, ide, limk2 and cpz genes and underexpression of chrna4 and sod1.

Conclusions: Two of the genes proposed in this paper, limk2 and cpz, have not been previously associated with schizophrenia, so future studies will be necessary to understand their possible role in the pathogenesis of this disease.