Effects of aerobic exercise training on cognitive function and cortical vascularity in monkeys

Abstract

This study examined whether regular exercise training, at a level that would be recommended for middle-aged people interested in improving fitness could lead to improved cognitive performance and increased blood flow to the brain in another primate species. Adult female cynomolgus monkeys were trained to run on treadmills for 1 h a day, 5 days a week, for a 5 month period (n=16; 1.9+/-0.4 miles/day). A sedentary control group sat daily on immobile treadmills (n=8). Half of the runners had an additional sedentary period for 3 months at the end of the exercise period (n=8). In all groups, half of the monkeys were middle-aged (10-12 years old) and half were more mature (15-17 years old). Starting the fifth week of exercise training, monkeys underwent cognitive testing using the Wisconsin General Testing Apparatus (WGTA). Regardless of age, the exercising group learned to use the WGTA significantly faster (4.6+/-3.4 days) compared to controls (8.3+/-4.8 days; P=0.05). At the end of 5 months of running monkeys showed increased fitness, and the vascular volume fraction in the motor cortex in mature adult running monkeys was increased significantly compared to controls (P=0.029). However, increased vascular volume did not remain apparent after a 3-month sedentary period. These findings indicate that the level of exercise associated with improved fitness in middle-aged humans is sufficient to increase both the rate of learning and blood flow to the cerebral cortex, at least during the period of regular exercise.

Figure 1

Schematic diagram of the experimental design. Maximal exercise test abbreviated as ‘max test’; submaximal exercise test abbreviated as ‘submax test’.

Figure 2

CD31 immunostaining of vasculature and sampling region. A, Immunostaining across the full depth of the precentral gyrus, showing a clear transition to reduced vascularization in white matter, demarcated by arrows (scale bar = 200 µm). B, Location of 8 sample regions in 4 equal zones through the primary motor cortex (CS = central sulcus; CgS = cingulate sulcus). C, Sampling grid superimposed on immunostained tissue. A blood vessel was counted if it was under the center of a grid point (+). The calculated volume fraction was equal to the total number of grid points over vessels divided by the total number of grid points in the reference area/volume. (Scale bar = 100 µm).

Figure 3

Plasma lactate concentrations in (A) middle-aged and (B) more mature monkeys, measured in runners (R) and run-stops (RS) before and after submaximal exercise testing, or in sedentary controls (S) before and after sitting on the treadmill. Week of testing appears below each pair of data bars. Solid black and open bars are pre-test plasma lactate concentrations, stippled and striped bars are post-test concentrations. Asterisks indicate a significant difference between pre- vs. post- exercise values within a specific experimental group. The plus sign indicates a significant difference between more mature and middle-aged monkeys.

Figure 4

Maximal speed attained during maximal exercise tests in (A) middle-aged adult and (B) more mature adult runners at the initiation of the training period (week 5, Maximal Exercise Test 1), during the training period (week 12, Maximal Exercise Test 2) and at the end of the training period (week 24, Maximal Exercise Test 3). Asterisks indicate a significant difference from the maximum speed attained at Maximal Exercise Test 1. Plus sign indicates a significant difference between middle-aged and mature runners. Note that only the Run-Stop animals were tested in Maximal Exercise Tests 4 (week 30) and 5 (week 36).

Figure 5

(A) Days of training required to learn to use the WGTA in runners (solid bar; n=8) and sedentary controls (open bar; n=8), (B) number of trials and (C) errors/trial made by runners and sedentary controls in the spatial delayed response task. Asterisk indicates a significant difference between groups.

Figure 6

Effects of exercise on volume fraction of CD31-immunostained vascular tissue in motor cortex of runners (solid bars), run-stops (striped bars) and controls (open bars). Asterisks indicate a significant difference between groups.