The effects of treadmill exercise on brain angiogenesis in ovariectomized rats

Abstract

Menopause is associated with vascular dysfunction attributed to reduced estrogen levels. Exercise has been proposed to promote angiogenesis and vascular dysfunction. However, studies of brain angiogenesis during menopause are limited. We analyzed the effects of exercise on angiogenesis-related factors in menopausal rat model. Twenty-week-old female Sprague-Dawley rats (N = 18) were randomly divided into a normal control group (N, n = 6), an ovariectomized control group (OVX, n = 6), and an ovariectomy + exercise group (OVX-EX, n = 6). Treadmill exercises were conducted in the OVX-EX group for 8 weeks (15-60 m/min, 1 h/day, and 5 days/week). The current study showed that the expression of angiogenesis-related factors (platelet-derived growth factor subunit A, B, vascular endothelial growth factor, angiopoietin 1, and angiopoietin 2) significantly decreased in the cortex of the OVX group. However, these factors were significantly restored in the cortex of the OVX-EX group after 8 weeks of treadmill exercise. In summary, estrogen deficiency causes vascular dysfunction by inhibiting the expression of angiogenesis-related factors. However, exercise can restore angiogenesis-related factors in OVX rats. Exercise eventually prevents vascular dysfunction in the brain and may help prevent cognitive dysfunction in menopausal women.

Keywords: angiogenesis; brain; exercise; menopause; ovariectomy.

FIGURE 1

17β‐Estradiol levels in serum at the beginning and end of experiment in different groups (n = 6). 17β‐Estradiol levels were analyzed using an ELISA kit. Values are expressed as mean ± SD for six rats. The paired sample t‐test was used for the comparison estradiol levels between groups at the beginning and end of experimental study, and the one‐way ANOVA was used for the comparison of the levels between groups at the end of experimental study. Normal, normal control group; OVX, ovariectomized group; OVX‐EX, ovariectomy + exercise group. * Significantly different from the normal control group at the end of study (p < 0.05). # Significantly different from baseline and end of experimental study in the OVX‐EX group (p < 0.05).

FIGURE 2

At the end of the experimental study, western blot was performed in the left cortex of rats (n = 4). (a) Representative bands of protein related to the angiogenesis factors, platelet derived growth factor (PDGF)‐A and B, and vascular endothermic growth factor (VEGF). (b) The band densities were normalized to that of actin. The one‐way ANOVA was used for the comparison of groups at the end of experimental study. Normal, normal control group; OVX, ovariectomized group; OVX‐EX, ovariectomy + exercise group. * Significantly different from the normal control group (p < 0.05). # Significantly different form the OVX control group (p < 0.05).

FIGURE 3

At the end of the experimental study, immunohistochemistry was performed to confirm the expression of platelet derived growth factor (PDGF)‐AB in the cortex of rats (n = 2). Representative immunohistochemical images showing the expression of PDGF‐AB in the cortex of rats. Arrowheads represent the area where PDGF‐AB is being expressed. Scale bar = 50 μm, magnification ×200. Normal, normal control group; OVX, ovariectomized group; OVX‐EX, ovariectomy + exercise group.

FIGURE 4

At the end of the experimental study, real‐time PCR was performed in the right cortex of rats (n = 4). (a) The expression of Ang1 mRNA in the brain tissues of rats. (b) The expression of Ang2 mRNA in the brain tissues of rats. The one‐way ANOVA was used for the comparison in groups at the end of experimental study. Normal, normal control group; OVX, ovariectomized group; OVX‐EX, ovariectomy + exercise group. * Significantly different from the normal control group (p < 0.05). # Significantly different form the OVX control group (p < 0.05).