Effects of 5-h multimodal stress on the molecules and pathways involved in dendritic morphology and cognitive function

• Plasma corticosterone level increased following 5-h multimodal stress.
• Mice exposed to the 5-h stress also demonstrated cognitive impairments.
• Dendritic and synaptic morphologies were altered after stress exposure.
• Several genes were related to the stress-induced changes in dendritic morphology.
• The Notch and TGF-B signaling pathways may be involved in stress response.

Stress induces cognitive impairments, which are likely related to the damaged dendritic morphology in the brain. Treatments for stress-induced impairments remain limited because the molecules and pathways underlying these impairments are unknown. Therefore, the aim of this study was to find the potential molecules and pathways related to damage of the dendritic morphology induced by stress. To do this, we detected gene expression, constructed a protein–protein interaction (PPI) network, and analyzed the molecular pathways in the brains of mice exposed to 5-h multimodal stress. The results showed that stress increased plasma corticosterone concentration, decreased cognitive function, damaged dendritic morphologies, and altered APBB1, CLSTN1, KCNA4, NOTCH3, PLAU, RPS6KA1, SYP, TGFB1, KCNA1, NTRK3, and SNCA expression in the brains of mice. Further analyses found that the abnormal expressions of CLSTN1, PLAU, NOTCH3, and TGFB1 induced by stress were related to alterations in the dendritic morphology. These four genes demonstrated interactions with 55 other genes, and configured a closed PPI network. Molecular pathway analysis use the Database for Annotation, Visualization, and Integrated Discovery (DAVID), specifically the gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG), each identified three pathways that were significantly enriched in the gene list of the PPI network, with genes belonging to the Notch and transforming growth factor-beta (TGF-B) signaling pathways being the most enriched. Our results suggest that TGFB1, PLAU, NOTCH3, and CLSTN1 may be related to the alterations in dendritic morphology induced by stress, and imply that the Notch and TGF-B signaling pathways may be involved.