Long-term exercise training improves memory in middle-aged men and modulates peripheral levels of BDNF and Cathepsin B

Abstract

Aging is accompanied by a decline in memory and other brain functions. Physical exercise may mitigate this decline through the modulation of factors participating in the crosstalk between skeletal muscle and the brain, such as neurotrophins and oxidative stress parameters. We aimed to determine whether long term exercise training (35 ± 15 years) promotes memory maintenance in middle-aged men, and to characterize the changes in neurotrophic factors and lipid oxidation markers in peripheral blood samples in both middle-aged and young men. The neuropsychological analysis showed significant improvements in memory through the Free and Cued Immediate Recall tests, in the middle-aged trained individuals when compared to the sedentary ones. We found a significant decrease in the resting serum BDNF and plasma Cathepsin B (CTSB) levels in the trained groups at both middle and young ages. BDNF and CTSB levels were inversely correlated with weekly hours of exercise. We also found a significant decrease in plasma malondialdehyde, an index of lipid peroxidation, in middle-aged and young trained subjects. The positive impact of long-term exercise training by delaying the onset of physiological memory loss and the associated neurotrophic and redox peripheral modulation, suggests the effectiveness of exercise as preventive strategy against age-related memory loss and neurodegeneration.

Figure 1

Free and cued selective reminding tests in middle-aged subjects. Effect of a long-term exercise training. FCSRT results in the MSG (Middle-Aged Sedentary Group) and MTG (Middle-Aged Trained Group). Number of words in the total immediate free recall test (A) and in the total immediate cued recall test (B). Bars represent mean ± SD. Statistical significance was assessed using two-tailed Student’s t-test. *p < 0.05 (C,D). Spearman’s correlation test between weekly hours of exercise and number of words in the total immediate free recall test (C) and total immediate cued recall test (D). For both (C,D), values inside the graph indicate the P value of the correlation.

Figure 2

Oxidative damage in young and middle-aged subjects. Effect of a long-term exercise training. Oxidative damage in the YSG (Young Sedentary Group), YTG (Young Trained Group), MSG (Middle-Aged Sedentary Group) and MTG (Middle-Aged Trained Group). (A) Densitometric analysis (a.u.: arbitrary units) for plasma protein carbonyl levels measured by Western Blotting. (B) Plasma MDA levels measured by HPLC. Bars represent mean ± SD. Statistical significance was assessed using Two-way ANOVA. ^&p < 0.05 factor exercise training.

Figure 3

BDNF serum levels and its correlation with malondialdehyde and weekly hours of exercise in young and middle-aged subjects. (A) BDNF resting serum levels were determined by ELISA in the YSG (Young Sedentary Group), YTG (Young Trained Group,), MSG (Middle-Aged Sedentary Group) and MTG (Middle-Aged Trained Group). Bars represent mean ± SD. Statistical significance was assessed using the Two-way ANOVA test. Bonferroni post-hoc test: *p < 0.05,***p < 0.001 compared to respective sedentary group; ^###p < 0.001 compared to respective young group. (B,C) Spearman’s correlation test between weekly hours of exercise and BDNF resting serum levels in young (B) and middle-aged (C) individuals. (D) Spearman’s correlation between resting serum levels of BDNF and plasma levels of MDA. For B, C, and D, values inside the graph indicate the P value of the correlation.

Figure 4

Cathepsin plasma levels and its correlation with malondialdehyde and weekly hours of exercise in young and middle-aged subjects. (A) Cathepsin B resting plasma levels were determined by ELISA in the YSG (Young Sedentary Group), YTG (Young Trained Group), MSG (Middle-Aged Sedentary Group) and MTG (Middle-Aged Trained Group). Bars represent mean ± SD. Statistical significance was assessed using Two-way ANOVA. ^$p < 0.05 factor age; ^&&&p < 0.001, factor exercise training. (B,C) Spearman’s correlation test between weekly hours of exercise and Cathepsin B resting plasma levels in young (B) and middle-aged (C) individuals. For (B and C), values inside the graph indicate the P value of the correlation.