Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong, Australia.
Sci Rep. 2023 Apr 4;13(1):5513. doi: 10.1038/s41598-023-32163-w.
Loss of function mutations in the gene encoding dystrophin elicits a hypersensitive fear response in mice and humans. In the dystrophin-deficient mdx mouse, this behaviour is partially protected by oestrogen, but the mechanistic basis for this protection is unknown. Here, we show that female mdx mice remain normotensive during restraint stress compared to a hypotensive and hypertensive response in male mdx and male/female wildtype mice, respectively. Partial dystrophin expression in female mdx mice (heterozygous) also elicited a hypertensive response. Ovariectomized (OVX) female mdx mice were used to explain the normotensive response to stress. OVX lowered skeletal muscle mass and lowered the adrenal mass and zona glomerulosa area (aldosterone synthesis) in female mdx mice. During a restraint stress, OVX dampened aldosterone synthesis and lowered the corticosterone:11-dehydrocorticosterone. All OVX-induced changes were restored with replacement of oestradiol, except that oestradiol lowered the zona fasciculata area of the adrenal gland, dampened corticosterone synthesis but increased cortisol synthesis. These data suggest that oestrogen partially attenuates the unconditioned fear response in mdx mice via adrenal and vascular function. It also suggests that partial dystrophin restoration in a dystrophin-deficient vertebrate is an effective approach to develop an appropriate hypertensive response to stress.
缺失功能的基因突变会导致肌营养不良蛋白编码基因，引发小鼠和人类的超敏恐惧反应。在肌营养不良蛋白缺乏的 mdx 小鼠中，这种行为部分受到雌激素的保护，但这种保护的机制尚不清楚。在这里，我们发现与雄性 mdx 和雄性/雌性野生型小鼠的低血压和高血压反应相比，束缚应激期间雌性 mdx 小鼠保持正常血压。雌性 mdx 小鼠（杂合子）的部分肌营养不良蛋白表达也引起了高血压反应。利用去卵巢（OVX）雌性 mdx 小鼠来解释对压力的正常血压反应。OVX 降低了雌性 mdx 小鼠的骨骼肌质量，并降低了肾上腺质量和肾小球带区面积（醛固酮合成）。在束缚应激期间，OVX 抑制了醛固酮的合成，降低了皮质酮：11-去氢皮质酮。所有 OVX 引起的变化都可以通过雌激素替代来恢复，除了雌激素降低了肾上腺的束状带区，抑制了皮质酮的合成，但增加了皮质醇的合成。这些数据表明，雌激素通过肾上腺和血管功能部分减弱了 mdx 小鼠的非条件恐惧反应。它还表明，在肌营养不良蛋白缺乏的脊椎动物中部分恢复肌营养不良蛋白是开发对压力的适当高血压反应的有效方法。
