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

Area of Science:

• Neuroscience
• Molecular Biology
• Psychiatry

Background:

• Prenatal stress (PS) is linked to offspring depression-like behaviors.
• The precise molecular mechanisms underlying this link remain unclear.
• CREB-regulated transcriptional coactivator 1 (CRTC1) is implicated in mood regulation.

Purpose of the Study:

• To investigate the role of CRTC1 signaling in depression-like behaviors observed in offspring exposed to prenatal stress.
• To determine if CRTC1 pathway alterations contribute to the behavioral and molecular changes induced by prenatal stress.

Main Methods:

• Male offspring rats exposed to prenatal stress were assessed for depression-like behaviors using the sucrose preference test (SPT), forced swimming test (FST), and open field test (OFT).
• Levels of CRTC1, nuclear CRTC1, cytoplasmic p-CRTC1, calcineurin, brain-derived neurotrophic factor (BDNF), and c-fos were measured in the hippocampus (HIP) and prefrontal cortex (PFC).
• mRNA levels of CRTC1, calcineurin, BDNF, and c-fos were quantified. Effects of fluoxetine treatment were evaluated.

Main Results:

• Prenatal stress offspring exhibited reduced sucrose preference and increased immobility, indicative of depression-like behaviors.
• Decreased total CRTC1, nuclear CRTC1, calcineurin, BDNF, and c-fos, alongside increased cytoplasmic p-CRTC1, were observed in the HIP and PFC.
• mRNA levels of CRTC1, calcineurin, BDNF, and c-fos were downregulated in stressed offspring. Fluoxetine treatment ameliorated some abnormal CRTC1 signaling.

Conclusions:

• Aberrant CRTC1 expression and/or phosphorylation activity in the hippocampus and prefrontal cortex are implicated in prenatal stress-induced depression-like behaviors.
• CRTC1 signaling pathway dysregulation is a potential mechanism linking prenatal stress to offspring depression.
• Fluoxetine shows potential in mitigating these stress-induced neurobiological changes.