Department of Anatomy, School of Medicine, College of Medicine, Kaohsiung Medical University, 100, Shih-Chuan 1st Road, Sanmin District, Kaohsiung 80708, Taiwan.
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, 100, Shih-Chuan 1st Road, Sanmin District, Kaohsiung 80708, Taiwan.
Int J Mol Sci. 2022 May 16;23(10):5531. doi: 10.3390/ijms23105531.
Hypertension is associated with blood-brain barrier alteration and brain function decline. Previously, we established the 2-kidney,1-clip (2K1C) hypertensive mice model by renin-angiotensin system (RAS) stimulating. We found that 2K1C-induced hypertension would impair hippocampus-related memory function and decrease adult hippocampal neurogenesis. Even though large studies have investigated the mechanism of hypertension affecting brain function, there remains a lack of efficient ways to halt this vicious effect. The previous study indicated that running exercise ameliorates neurogenesis and spatial memory function in aging mice. Moreover, studies showed that exercise could normalize RAS activity, which might be associated with neurogenesis impairment. Thus, we hypothesize that running exercise could ameliorate neurogenesis and spatial memory function impairment in the 2K1C-hypertension mice. In this study, we performed 2K1C surgery on eight-weeks-old C57BL/6 mice and put them on treadmill exercise one month after the surgery. The results indicate that running exercise improves the spatial memory and neurogenesis impairment of the 2K1C-mice. Moreover, running exercise normalized the activated RAS and blood-brain barrier leakage of the hippocampus, although the blood pressure was not decreased. In conclusion, running exercise could halt hypertension-induced brain impairment through RAS normalization.
高血压与血脑屏障改变和脑功能下降有关。此前，我们通过肾素-血管紧张素系统（RAS）刺激建立了 2 肾 1 夹（2K1C）高血压小鼠模型。我们发现，2K1C 诱导的高血压会损害与海马相关的记忆功能，并减少成年海马神经发生。尽管大量研究已经探讨了高血压影响大脑功能的机制，但仍然缺乏有效方法来阻止这种恶性循环。先前的研究表明，跑步运动可以改善衰老小鼠的神经发生和空间记忆功能。此外，研究表明，运动可以使 RAS 活性正常化，这可能与神经发生受损有关。因此，我们假设跑步运动可以改善 2K1C 高血压小鼠的神经发生和空间记忆功能障碍。在这项研究中，我们对 8 周龄 C57BL/6 小鼠进行了 2K1C 手术，并在手术后一个月让它们进行跑步机运动。结果表明，跑步运动改善了 2K1C 小鼠的空间记忆和神经发生障碍。此外，尽管血压没有降低，但跑步运动使海马中激活的 RAS 和血脑屏障渗漏正常化。总之，跑步运动可以通过 RAS 正常化来阻止高血压引起的脑损伤。
