Impact of exercise on brain-bone marrow interactions in chronic stress: potential mechanisms preventing stress-induced hypertension
Impact of exercise on brain-bone marrow interactions in chronic stress: potential mechanisms preventing stress-induced hypertension
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运动对慢性应激中脑-骨髓相互作用的影响：预防应激性高血压的潜在机制
DOI：
10.1152/physiolgenomics.00168.2022
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发表时间：
2023
影响因子：
4.6
通讯作者：
Hidefumi Waki
中科院分区：
文献类型：
--
作者：
Thu Van Nguyen;Ko Yamanaka;Keisuke Tomita;Jasenka Zubcevic;Sabine S S Gouraud;Hidefumi Waki
我们研究了慢性束缚应激的影响和日常锻炼对脑-骨髓（BM）相互作用的分子基础的反作用，特别是专注于下丘脑室旁核（PVN）。雄性Wistar大鼠分为对照组、束缚应激组和应激+每日自发运动组。通过RT-PCR和微阵列技术分别检测BM和下丘脑基因表达谱。通过流式细胞术研究炎性血细胞群。通过免疫组织化学方法，我们检测了BM衍生的C-C趋化因子受体2（CCR 2）表达的小胶质细胞在大鼠PVN的存在。与对照组相比，两个限制组的BM炎性因子（如白细胞介素1 β和CCR 2）的基因表达水平以及炎性血细胞群均显著升高。有趣的是，慢性束缚应激单独激活了BM来源的表达CCR 2的小胶质细胞向PVN的募集，而每日自发运动阻止了它。一个值得注意的发现是，束缚应激上调了下丘脑基质金属蛋白酶3（MMP 3）的相对基因表达，这增加了血脑屏障（BBB）的通透性，并且运动设法使其正常化。此外，一些直接参与促进细胞迁移的下丘脑基因的相对表达被日常运动下调。我们的研究结果表明，每日自发运动可以减少BM衍生的CCR 2表达的小胶质细胞进入PVN的数量，通过预防应激诱导的下丘脑基因表达的变化。新&值得注意的是，慢性束缚应激可以上调大鼠下丘脑MMP 3基因表达，而每日自发运动可以预防这种应激诱导的作用。每日自发运动可预防应激诱导的BM源性炎性细胞向大鼠PVN的募集。应激诱导的下丘脑MMP 3基因表达增加可能是BBB损伤的原因，从而使BM衍生的炎性细胞被招募并在大鼠PVN中积累，并随后参与应激诱导的高血压的发病。
We examined the effect of chronic restraint stress and the counteractive effects of daily exercise on the molecular basis of the brain-bone marrow (BM) interactions, by especially focusing on the paraventricular nucleus (PVN) of the hypothalamus. Male Wistar rats were assigned into control, restraint stress, and stress + daily spontaneous exercise (SE) groups. BM and hypothalamic gene expression profiles were examined through the undertaking of RT-PCR and microarrays, respectively. The inflammatory blood cell population was investigated through flow cytometry. Through the use of immunohistochemistry, we examined the presence of BM-derived C-C chemokine receptor type 2 (CCR2)-expressing microglial cells in the rat PVN. The gene expression levels of BM inflammatory factors such as those of interleukin 1 beta and CCR2, and the inflammatory blood cell population were found to be significantly higher in both restrained groups compared with control group. Interestingly, chronic restraint stress alone activated the recruitment of BM-derived CCR2-expressing microglial cells into the PVN, whereas daily spontaneous exercise prevented it. A notable finding was that restraint stress upregulated relative gene expression of hypothalamic matrix metalloproteinase 3 (MMP3), which increases the permeability of the blood-brain barrier (BBB), and that exercise managed to normalize it. Moreover, relative expression of some hypothalamic genes directly involved in the facilitation of cell migration was downregulated by daily exercise. Our findings suggest that daily spontaneous exercise can reduce the numbers of BM-derived CCR2-expressing microglial cells into the PVN through the prevention of stress-induced changes in the hypothalamic gene expression.NEW & NOTEWORTHYChronic restraint stress can upregulate MMP3 gene expression in the rat hypothalamus, whereas daily spontaneous exercise can prevent this stress-induced effect. Stress-induced BM-derived inflammatory cell recruitment into the rat PVN can be prevented by daily spontaneous exercise. Stress-induced increase of hypothalamic MMP3 gene expression may be responsible for BBB injury, thereby allowing for BM-derived inflammatory cells to be recruited and to accumulate in the rat PVN, and to be subsequently involved in the onset of stress-induced hypertension.