Maternal separation stress drastically decreases expression of transthyretin in the brains of adult rat offspring

Adversity in early life has been recognized as a risk factor for psychiatric disorders. In experimental animals, maternal separation (MS) during the neonatal period has been shown to be critical for susceptibility to stress in adult offspring. In this study, we used DNA microarray analysis of rat hippocampal samples to investigate differential gene expression caused by 8-hour MS (MS-8h) every other day during the neonatal period. We found 15 up-regulated and 9 down-regulated genes. We added samples from a daily 15-minute MS (MS-15m) group and performed quantitative real-time PCR to validate the results. Expression of transthyretin (TTR), which is specifically expressed in the choroid plexus (CP), was drastically reduced in the MS-8h group. Two other CP-enriched genes, angiotensin I converting enzyme I and insulin-like growth factor II (IGF-II), were also significantly down-regulated in the MS-8h rats, while significant reduction of IGF-II expression was also found in the MS-15m group. These MS-induced differential gene expressions could be involved in the molecular mechanisms of stress susceptibility. Our findings indicate that the CP, in addition to the neuronal and glial system, might play an important role in determining stress susceptibility.