4.7 Article

Exercise Normalized the Hippocampal Renin-Angiotensin System and Restored Spatial Memory Function, Neurogenesis, and Blood-Brain Barrier Permeability in the 2K1C-Hypertensive Mouse

Journal

Publisher

MDPI
DOI: 10.3390/ijms23105531

Keywords

hypertension; 2-kidney; 1-clip; renin-angiotensin system; exercise; neurogenesis; blood-brain barrier

Funding

  1. Kaohsiung Medical University Research Foundation [KMU-Q109007, KMU-Q110009A, KMU-M111022]
  2. Ministry of Science and Technology, Taiwan [MOST108-2320-B-037-040-MY2]
  3. Tzu Hui Institute of Technology [THIT-109007, THIT-110005]

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This study investigates the effect of running exercise on 2K1C-induced hypertension in mice. The results show that running exercise improves spatial memory and neurogenesis impairment, normalizes RAS activity, and reduces blood-brain barrier leakage, indicating its potential in preventing hypertension-induced brain impairment.
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.

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