Impact of exercise on brain-bone marrow interactions in chronic stress: potential mechanisms preventing stress-induced hypertension

ABSTRACT: Brain-bone marrow interactions play a crucial role in stress response. However, it is not known whether the sustained increase in blood pressure caused by chronic stress is associated with changes occurring in these brain-bone marrow interactions. We, herein, examined the effect of chronic restraint stress on the molecular basis of the brain-bone marrow interactions, by especially focusing on the paraventricular nucleus (PVN) of the hypothalamus; a well-established blood pressure control center. Male Wistar rats were randomly assigned into control (Co) and restraint stress (St) groups. Furthermore, since daily exercise has been shown to exert anti-stress and anti-hypertensive effects, a stress + exercise (SE) group was also assessed. Bone marrow and hypothalamic gene expression profiles were examined through the undertaking of reverse transcription polymerase chain reaction and microarrays, respectively. The inflammatory blood cell population was investigated through flow cytometry. Moreover, through the use of immunohistochemistry, we examined the presence of bone marrow-derived C-C chemokine receptor type 2 (CCR2)-expressing microglial cells in the rat PVN. The gene expression levels of bone marrow inflammatory factors such as those of interleukin 1 beta and CCR2 were found to be significantly higher in both the St and the SE group rats (when compared with those of the Co group rats). The inflammatory blood cell population was significantly higher in the restrained groups (St and SE) compared with the Co group. Chronic restraint stress activated the recruitment of bone marrow-derived CCR2-expressing microglial cells into the PVN, whereas daily exercise prevented it. We identified 578 genes that were differentially expressed to a significant level (>1.5-fold difference; p<0.05) in the hypothalami of rats belonging to the three experimental groups. From those 578 genes, 49 genes were identified as differentially expressed between the St and the Co groups, 551 genes were identified as differentially expressed between the SE and the Co groups, and 153 genes were identified as differentially expressed between the St and the SE groups. A notable finding was that restraint stress upregulated the matrix metalloproteinase 3 gene (Mmp3) expression, and that daily spontaneous exercise managed to normalize it. Our findings provide new insights into the effects of restraint stress and of exercise on the regulation of cardiovascular homeostasis through brain-bone marrow interactions. A stress-induced increase of the hypothalamic Mmp3 expression was assumed to increase the permeability of the blood-brain barrier to bone marrow-derived CCR2-expressing microglial cells, which in turn may play a role in the onset of stress-induced hypertension. On the other hand, daily exercise may prevent these pathophysiological events via a downregulation of the Mmp3 expression in the rat hypothalamus.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE220747 | GEO | 2023/02/02

REPOSITORIES: GEO