Sex-Specific Effects of Early-Life Stress Exposure on Memory Performance and the Medial Prefrontal Cortex...

Area of Science:

• Neuroscience
• Developmental Psychology
• Molecular Biology

Background:

• Early life stress (ELS) is a known risk factor for cognitive and executive dysfunction.
• The medial prefrontal cortex (mPFC), crucial for working memory, is vulnerable to ELS due to its late development.
• Understanding ELS effects on mPFC-dependent functions is vital for addressing developmental disorders.

Purpose of the Study:

• To investigate the impact of ELS on PFC-dependent memory.
• To analyze mPFC transcriptomic profiles following ELS exposure.
• To compare sex-specific effects of ELS on memory and gene expression.

Main Methods:

• Mice were exposed to maternal separation and limited bedding from postnatal day 2 to 15.
• Working memory and short-term recognition memory were assessed using the Y-maze and object in place (OIP) tasks.
• RNA sequencing (RNA-seq) was employed to analyze mRNA level alterations in the mPFC.

Main Results:

• ELS increased maternal care and nest exits.
• Both sexes showed OIP task impairments; females additionally performed worse in the Y-maze.
• Transcriptomic analysis revealed 13 differentially expressed genes in females (chaperone-mediated protein folding) and 4 in males.

Conclusions:

• ELS alters maternal behavior and induces memory impairments and transcriptomic changes.
• Females exhibit more pronounced memory deficits and mPFC alterations compared to males following ELS.
• These findings highlight sex-specific vulnerabilities to early life stress in brain development and function.