Early-Life Psychological Stress Impairs Spatial Learning and Memory in Rats by Altering the Hippocampal Proteome.

Area of Science:

• Neuroscience
• Molecular Biology
• Proteomics

Background:

• Early-life stress (ELPS) is linked to anxiety, pessimism, and cognitive decline.
• The hippocampus, crucial for learning and memory, is significantly impacted by ELPS.
• Understanding the molecular mechanisms of ELPS on hippocampal function is vital.

Purpose of the Study:

• To elucidate the molecular mechanisms of ELPS on hippocampal learning and memory in rats.
• To investigate age-dependent effects of ELPS on cognitive function.
• To identify differentially expressed proteins and associated pathways in the hippocampus post-ELPS.

Main Methods:

• An ELPS model was applied to juvenile rats.
• Spatial learning and memory were assessed using the Morris Water Maze (MWM) test.
• Proteomic analysis involved two-dimensional gel electrophoresis (2DE) and UPLC-ESI-Q-TOF-MS, followed by KEGG pathway and PPI network analysis.

Main Results:

• ELPS induced age-dependent spatial cognitive deficits, with more severe impairments in adult rats.
• Juvenile rats showed mild spatial learning deficits, while adult rats exhibited significant deficits in both learning and memory.
• Proteomic analysis identified 10 differentially expressed proteins (DEPs) in the hippocampus, linked to pathways including Prion disease and Alzheimer disease.

Conclusions:

• ELPS causes lasting detrimental effects on spatial cognitive function, with deficits progressing from juvenile to adult stages.
• Consistent proteomic alterations in the hippocampus correlate with age-dependent cognitive impairments.
• The study highlights the persistent impact of early-life stress on hippocampal function and cognitive health.