Glucocorticoid Signaling-Associated Gene Expression in the Hippocampus and Frontal Cortex of Chronically Isolated Normotensive and Hypertensive Rats and the Responsiveness to Acute Restraint Stress.

Genotypic characteristics may determine the body's response to stressful conditions as well as its susceptibility to cardiovascular diseases and stroke. Old age worsens the course of these diseases, and often concomitant hypertension can negatively affect brain function, especially in cases of social isolation. In this work, we studied how social isolation and hypertension affect the transcription activity of genes associated with glucocorticoid signaling in the rat brain. The study was performed on 10-month-old rats of the outbred Wistar stock (n = 48) and the inbred spontaneously hypertensive (SHR) strain (n = 28). The animals of each genotype were divided into groups, one of which was kept in home cages in groups of 3-4 individuals, and the other in single cages for 3 months. Physiological parameters and plasma corticosterone were controlled before the start and after 3 months of isolation. Each group was additionally divided into two subgroups: one subjected to 1 h of restraint stress, and changes in blood glucose and corticosterone levels were assessed. At the end, the levels of Nr3c1, Nr3c2, Hsd11b1, and Fkbp5 mRNAs were measured in the hippocampus and frontal cortex using the Q-PCR technique. After isolation, weight gain stopped in SHRs, although blood pressure did not change, and heart rate increased in rats of both genotypes. In response to restraint, there was practically no increase in corticosterone in isolated Wistar rats, whereas in SHRs, there were significant glucose and corticosterone responses. Significant disruptions in the system responsible for corticosterone-activated signaling cascades were found in the brains of SHR rats. The transcriptional activity of genes encoding corticosterone receptors and proteins regulating their action was reduced in the hippocampus and frontal cortex in SHRs compared to Wistar rats. However, neither isolation nor acute stress significantly affected the contents of transcripts studied. Meanwhile, after isolation, the relationships between the expression of these genes changed significantly, in different directions, in rats of the studied genotypes, both within and between brain structures. Thus, the SHR genotype is associated with persistent changes in the brain that affect the expression of glucocorticoid-associated genes. This indicates a more complex regulation of the stress response, not limited only by the feedback system within the hypothalamic-pituitary-adrenocortical or sympatho-adrenomedullary systems, but operated at the level of the limbic system and the cerebral cortex.