Differential Regulation of Proteins Related to the Blood–Brain Barrier in Stress-Resilient and Stress-Susceptible Mice

Abstract

Stress is considered a primary contributor to mood disorders, such as depression. Therefore, preclinical research encompasses the biochemical and molecular aspects of stress. In the present study, we investigated the effects of restraint stress (RS) on three strains of mice with varying susceptibility to RS: transgenic mice lacking the gene encoding the noradrenergic transporter (NET-KO) and Swiss SWR/J, both displaying a stress-resilient phenotype, and C57Bl/6J (WT), which is stress-susceptible. In silico analysis of a group of microRNAs (miRNAs) differentiating these phenotypes indicated that their target mRNAs encode various proteins that are involved in maintaining the integrity of the blood–brain barrier (BBB). Further analyses using Custom TaqMan Gene Expression Array Cards revealed alterations in these mRNAs in four brain regions of mice subjected to RS. Protein levels were examined with immunohistofluorescence and indicated changes in the levels of two key proteins, claudin-5 (CLDN5) and caveolin-1 (CAV1), and their co-localization with the endothelial cell marker CD31 protein. Additionally, we used fluorescein sodium salt to examine BBB permeability in the mouse strains and found higher permeability in stress-susceptible animals. The most intriguing finding was the differential expression of Cav1 mRNA and protein levels in the brain regions of stress-resilient mice compared to the stress-susceptible strain. This suggests that CAV1 may play an important role in the BBB of stress-resilient individuals under stress conditions.