Decreased plasma brain-derived neurotrophic factor and vascular endothelial growth factor concentrations during military training

Abstract

Decreased concentrations of plasma brain-derived neurotrophic factor (BDNF) and serum BDNF have been proposed to be a state marker of depression and a biological indicator of loaded psychosocial stress. Stress evaluations of participants in military mission are critically important and appropriate objective biological parameters that evaluate stress are needed. In military circumstances, there are several problems to adopt plasma BDNF concentration as a stress biomarker. First, in addition to psychosocial stress, military missions inevitably involve physical exercise that increases plasma BDNF concentrations. Second, most participants in the mission do not have adequate quality or quantity of sleep, and sleep deprivation has also been reported to increase plasma BDNF concentration. We evaluated plasma BDNF concentrations in 52 participants on a 9-week military mission. The present study revealed that plasma BDNF concentration significantly decreased despite elevated serum enzymes that escaped from muscle and decreased quantity and quality of sleep, as detected by a wearable watch-type sensor. In addition, we observed a significant decrease in plasma vascular endothelial growth factor (VEGF) during the mission. VEGF is also neurotrophic and its expression in the brain has been reported to be up-regulated by antidepressive treatments and down-regulated by stress. This is the first report of decreased plasma VEGF concentrations by stress. We conclude that decreased plasma concentrations of neurotrophins can be candidates for mental stress indicators in actual stressful environments that include physical exercise and limited sleep.

Figure 1. Schedule of VAS questionnaire estimation, sleep evaluations, and blood examinations.

VAS questionnaires and blood samples were collected at three time points; before, during, and after training. Sleep was evaluated at two time points; before and during training. The time point of before the training was two days before initiation of training, during training was 2 weeks after the start of base training, and after the training was 3–5 days after cessation of the training period.

Figure 2. Stress (A; F_2,54 = 34.8) and fatigue (B; F_2,54 = 21.5) rated on the visual analog scale (VAS) are plotted before, during, and after training.

The results of plasma brain-derived neurotrophic factor (BDNF, C; F_2,51 = 7.8) and vascular endothelial growth factor (VEGF, D; F_2,54 = 20.7) are plotted before, during, and after training. Significant differences between groups are indicated as *p<0.05, **p<0.01, and ***p<0.001 using repeated one-way ANOVA followed by post hoc Tukey’s multiple comparison tests.

Figure 3. Plasma creatine phosphokinase (CPK; A, F_2,53 = 42.8) and lactate dehydrogenase (LDH; B, F_2,53 = 92.1) are plotted before, during, and after training.

Total sleep time (C), deep sleep time (D), and HF superior time (E) are plotted before and during training. Significant differences between the two groups in C, D, and E were evaluated using two-tailed paired Student’s t-tests. Significant differences between groups are indicated as *p<0.05, **p<0.01, and ***p<0.001.

Figure 4. The relationship between ΔBDNF and Δstress (A), ΔBDNF and Δfatigue (B), ΔBDNF and ΔCPK (C), and ΔBDNF and Δsleep (D) are plotted.

The values before training were subtracted from the values during the training and are expressed as Δvalues. No significant correlations were found in the four combinations.

Figure 5. The relationship between ΔVEGF and Δstress (A), ΔVEGF and Δfatigue (B), ΔVEGF and ΔCPK (C), and ΔVEGF and Δsleep (D) are plotted.

The values before training were subtracted from the values during training and were expressed as Δvalues. A significant negative correlation was noted between ΔVEGF and Δfatigue (B; R = −0.375, p = 0.003).