Striatal development involves a switch in gene expression networks, followed by a myelination event: implications for neuropsychiatric disease

Abstract

Abnormal development of striatal neurons is thought to be part of the pathology underlying psychiatric illness. We studied striatal gene expression patterns during an active striatal maturation period, the first two postnatal weeks in the rat. This parallels human striatal development during the second trimester, when prenatal stress is thought to lead to increased risk for neuropsychiatric disorders. Using subtractive hybridization and quantitative real‐time PCR, we characterize the developmental expression of more than 60 genes, many not previously known to play a role in neuromaturation. We show that during the first two postnatal weeks in the rat, an early gene expression network that lacks key striatal‐specific signaling pathways is downregulated and replaced by a mature gene expression network, containing key striatal‐specific genes, which confer functional identity to these neurons. Hence, early postnatal striatal neurons lack many of their key characteristics. This maturation process is followed by a rise in the expression of myelination genes, indicating a striatal‐specific myelination event. This strictly controlled developmental program is likely to be susceptible to disruption by external factors. Alterations in its normal progression may play a role in the etiology of neuropsychiatric disease. Indeed, this period is known to be a susceptibility period in both humans and rats.