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. 2017 Jul 22;8(39):65860-65875.
doi: 10.18632/oncotarget.19505. eCollection 2017 Sep 12.

Effects of exercise on capillaries in the white matter of transgenic AD mice

Yi Zhang  1   2   3 , Feng-Lei Chao  2   3 , Chun-Ni Zhou  1   2   3 , Lin Jiang  1   2   3 , Lei Zhang  2   3 , Lin-Mu Chen  2   3 , Yan-Min Luo  1   2   3 , Qian Xiao  1   2   3 , Yong Tang  2   3
Affiliations

Effects of exercise on capillaries in the white matter of transgenic AD mice

Yi Zhang et al. Oncotarget. .

Abstract

Previous studies have shown that exercise can prevent white matter atrophy in APP/PS1 transgenic Alzheimer's disease (AD) mice. However, the mechanism of this protective effect remains unknown. To further understand this issue, we investigated the effects of exercise on the blood supply of white matter in transgenic AD mice. Six-month-old male APP/PS1 mice were randomly divided into a control group and a running group, and age-matched non-transgenic littermates were used as a wild-type control group. Mice in the running group ran on a treadmill at low intensity for four months. Then, spatial learning and memory abilities, white matter and white matter capillaries were examined in all mice. The 10-month-old AD mice exhibited deficits in cognitive function, and 4 months of exercise improved these deficits. The white matter volume and the total length, total volume and total surface area of the white matter capillaries were decreased in the 10-month-old AD mice, and 4 months of exercise dramatically delayed the changes in these parameters in the AD mice. Our results demonstrate that even low-intensity running exercise can improve spatial learning and memory abilities, delay white matter atrophy and protect white matter capillaries in early-stage AD mice. Protecting capillaries might be an important structural basis for the exercise-induced protection of the structural integrity of white matter in AD.

Keywords: Alzheimer’s disease; capillary; running exercise; stereology; white matter.

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Conflict of interest statement

CONFLICTS OF INTEREST The authors declare no competing interests.

Figures

Figure 1
Figure 1
(A) The tracked locations of the Wild-type, APP/PS1 Control and APP/PS1 Runner mice in the hidden platform test. The Roman numerals (I, II, III, and IV) represent the first, second, third, and fourth quadrants, respectively, of the Morris water maze. (B) The escape latencies of the Wild-type, APP/PS1 Control and APP/PS1 Runner mice in the Morris water maze positioning navigation test. The 1,2,3,4,5 and 6 represent the latency day. Each point represents the average of four escape latencies (mean ± SEM). The asterisk (*) indicates the escape latency of the Wild-type mice compared with that of the APP/PS1 Control group in the Morris water maze positioning navigation test. The pound sign (#) indicates the escape latency of the APP/PS1 Runner mice compared with that of the APP/PS1 Control mice in the Morris water maze positioning navigation test. ** p < 0.01. #p < 0.05. (C) The platform-crossing frequency of the Wild-type, APP/PS1 Control and APP/PS1 Runner mice (mean ± SEM) in the probe trial tests. * p < 0.05. ** p < 0.01.
Figure 2
Figure 2. The total white matter volume of the Wild-type, APP/PS1 Control and APP/PS1 Runner mice (mean ± SD)
** p < 0.01.
Figure 3
Figure 3
(A) The white matter capillaries of the 10-month-old Wild-type mice. (B) The white matter capillaries of the 10-month-old APP/PS1 Control mice. (C) The white matter capillaries of the 10-month-old APP/PS1 Runner mice. Bar = 10 μm.
Figure 4
Figure 4
(A) The total white matter capillary length of the Wild-type, APP/PS1 Control and APP/PS1 Runner mice (mean ± SD). ** p < 0.01. (B) The total white matter capillary volume of the Wild-type, APP/PS1 Control and APP/PS1 Runner mice (mean ± SD). * p < 0.05, ** p < 0.01. (C) The total white matter capillary surface area of the Wild-type, APP/PS1 Control and APP/PS1 Runner mice (mean ± SD). ** p < 0.01.
Figure 5
Figure 5. An illustration of the gene identification results obtained by genotyping
The minus sign (-) indicates that this mouse expresses neither the APPswe gene nor the PSEN1 gene. The plus sign (+) indicates that this mouse expresses both the APPswe and PSEN1 genes.
Figure 6
Figure 6
(A) One of the successive 1-mm-thick cerebral sections. Bar = 500 μm. (B) A point grid was randomly placed on one of the successive equidistant brain sections, and the points contacting white matter were counted. The arrow (←) indicates one of the counted points. Bar = 500 μm. (C) The point grid was randomly superimposed on the section, and the points contacting white matter were sampled. The circles (○) indicate the sampled white matter. Bar = 500 μm.
Figure 7
Figure 7
(A) An unbiased counting frame was randomly placed on the view of the white matter, and the capillary profiles inside the counting frame were counted, including those crossing the inclusion lines (green lines) but not crossing the exclusion lines (red lines). The stars (★) indicate counted capillaries. Bar = 10 μm. (B) A point grid was randomly placed on the view of the white matter, and the number of points contacting white matter and the number of points contacting capillaries were counted. The arrows (→) indicate the counted points. Bar = 10 μm. (C) Test lines were superimposed on the view of the white matter, and the number of intersections between the test lines and the capillary luminal surfaces was counted. The arrows (← & →) indicate the counted intersections between the test lines and the capillaries. Bar = 10 μm.
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