CRTC1 signaling involvement in depression-like behavior of prenatally stressed offspring rat

Abstract

A large body of literature has demonstrated that prenatal stress (PS) can induce depression-like behavior in the offspring. However, the underlying mechanism remains largely unknown. CREB-regulated transcriptional coactivator 1(CRTC1) has recently been shown to involve in mood regulation. This research aims to investigate whether CRTC1 signaling was involved in the depression-like behavior of prenatally stressed offspring rats. Sucrose preference test (SPT), forced swimming test (FST) and open field test (OFT) were adopted to test the depression-like behavior in the male offspring rats, and CRTC1 signaling was measured. The results showed that there were significantly reduced sucrose intake in SPT and prolonged immobility time in FST in PS-exposure offspring rats. It was also found decreased levels of total CRTC1, nuclear CRTC1, calcineurin, brain-derived neurotrophic factor (BDNF) and c-fos, but increased cytoplasmic p-CRTC1 in the hippocampus (HIP) and prefrontal cortex (PFC) of the offspring rats. Furthermore, the mRNA level of CRTC1, calcineurin, BDNF, c-fos were down-regulated. Abnormal expression of CRTC1 signaling could be alleviated by fluoxetine treatment. In conclusion, our research indicated that the aberration of CRTC1 expression and/or phosphorylation activity might play a vital role in PS-induced depression-like behavior of offspring rats.