Early postnatal striatal gene expression networks in rat: relevance to schizophrenia

Abstract

Abnormal striatal development is thought to play an important role in a number of diseases, including schizophrenia. In humans, stress during the second trimester of pregnancy leads to increased risk for schizoaffective disorders in the offspring. This is period of active development of the striatum and corresponds to the second postnatal week of striatal development in rat. We show that during the first two postnatal weeks in rat an entire gene expression network becomes down‐regulated and replaced by a mature gene expression network. Using subtractive hybridization, we identified 31 additional genes involved in this process, including 12 novel transcripts with strict developmental expression. We show that in an established schizophrenia model in rat, this developmental process is altered and results in overexpression of the dopamine 2 receptor (D2R) during the second postnatal week, with no change in expression of D1R or other genes. This may play an important role in the development of a schizophrenia‐like phenotype, as striatal D2R upregulation has been shown to cause dysregulation of the prefrontal cortex.