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. 2009 Sep;35(3):426-32.
doi: 10.1016/j.nbd.2009.06.002. Epub 2009 Jun 12.

Effects of voluntary and forced exercise on plaque deposition, hippocampal volume, and behavior in the Tg2576 mouse model of Alzheimer's disease

Carla M Yuede  1 , Scott D Zimmerman, Hongxin Dong, Matthew J Kling, Adam W Bero, David M Holtzman, Benjamin F Timson, John G Csernansky
Affiliations

Effects of voluntary and forced exercise on plaque deposition, hippocampal volume, and behavior in the Tg2576 mouse model of Alzheimer's disease

Carla M Yuede et al. Neurobiol Dis. 2009 Sep.

Abstract

We examined the effects of voluntary (16 weeks of wheel running) and forced (16 weeks of treadmill running) exercise on memory-related behavior, hippocampal volume, thioflavine-stained plaque number, and soluble Abeta levels in brain tissue in the Tg2576 mouse model of Alzheimer's disease (AD). Voluntary running animals spent more time investigating a novel object in a recognition memory paradigm than all other groups. Also, voluntary running animals showed fewer thioflavine S stained plaques than all other groups, whereas forced running animals showed an intermediate number of plaques between voluntary running and sedentary animals. Both voluntary and forced running animals had larger hippocampal volumes than sedentary animals. However, levels of soluble Abeta-40 or Abeta-42 did not significantly differ among groups. The results indicate that voluntary exercise may be superior to forced exercise for reducing certain aspects of AD-like deficits - i.e., plaque deposition and memory impairment, in a mouse model of AD.

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Figures

Figure 1
Figure 1. Experimental Timeline
Time line of experimental manipulations. Mice in exercise groups began daily 1 hr sessions beginning at 5 months of age and continuing until 9 months of age. Behavioral testing was conducted on 3 consecutive days and tissue was collected immediately following behavioral testing on the last day.
Figure 2
Figure 2. Object Recognition Procedure
Schematic drawing of novelty-preference paradigm. Mice should spend a roughly equal percentage of their total investigation time investigating both objects during the sample trial and a higher percentage of their total investigation time on the novel object during the test trial. Pilot tests were conducted to identify objects of equal interest to this strain of mice.
Figure 3
Figure 3. Object Recognition Sample Trial
Object investigation during the sample trial. (A) No significant differences were observed between groups in total time spent investigating both objects, and all groups spent an average of 220 sec in active investigation of the objects during the 600 sec trial. (B) All groups spent an equal percentage of their investigation time on both copies of the object during the sample trial. Dashed line represents chance level of investigation.
Figure 4
Figure 4. Object Recognition Test Trial
Object investigation during the test trial. (A) No significant differences were observed among groups in total time spent in active investigation of the objects during the test trial. Average investigation time was 199 sec during the 600 sec trial. (B) Animals in the VOL group showed a significant preference for the novel object compared to all other groups. (* denotes p < 0.05). Mice exposed to voluntary running were the only group to show significant differences in investigation time between the novel object and the familiar object. Dashed line represents chance level of investigation.
Figure 5
Figure 5. Thioflavine-stained Plaque Count
Quantative analysis of Thioflavine S stained plaques in the brains of Tg2576 mice at 9 months of age. Plaque number was significantly decreased in VOL group compared to all other groups. The FOR group had fewer plaques than the SED group. (* denotes p < 0.05).
Figure 6
Figure 6. Hippocampal Volume
Hippocampal volume measurements. (A) Both VOL and FOR groups show increased hippocampal volume after 16 weeks of exercise compared to SED controls. (* denotes p < 0.05). (B) Photograph of coronal hemisection containing Analyze 8.0 stereology module grid. Points on the grid are spaced 8 pixels apart on the X and Y axes, and total number of pixels encompassing the hippocampal formation in each brain were calculated to obtain hippocampal volume using Cavalieri’s principle.
See this image and copyright information in PMC

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