Decreased Plasma Brain-Derived Neurotrophic Factor and Vascular Endothelial Growth Factor Concentrations during Military Training

Go Suzuki,Tetsuo Yamamoto,Keiji Mitani,Daniel Scott,Masashi Nibuya,Gentaro Tsumatori,Shinichi Tokuno,Yasuo Mukai,Kunio Shimizu,Toru Ishida,Stephen D Ginsberg

doi:10.1371/journal.pone.0089455

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.

Highlights

The loaded stress levels of each participant in an occupational environment are variable, and precise stress management for an individual is important
We examined plasma brain-derived neurotrophic factor (BDNF) and plasma vascular endothelial growth factor (VEGF) concentrations before, during, and after military training, and compared them with levels of self-evaluated stress, fatigue levels, and other biological parameters of muscle-escaping enzymes and sleep
The current study revealed a significant decrease in plasma BDNF concentrations 3 weeks after beginning military training

Summary

Introduction

The loaded stress levels of each participant in an occupational environment are variable, and precise stress management for an individual is important. Self-questionnaires are effective tools to assess the current stress status, they are sometimes not effective because they are based on subjective evaluation. To support and validate questionnaire results, biomarkers that reflect the severity of mental stress are needed. We examined plasma brain-derived neurotrophic factor (BDNF) and plasma vascular endothelial growth factor (VEGF) concentrations before, during, and after military training, and compared them with levels of self-evaluated stress, fatigue levels, and other biological parameters of muscle-escaping enzymes and sleep. Decreased BDNF expression induced by stress was first found in the hippocampus in animal experiments [1], [2]. Serum BDNF is mostly derived from platelets in coagulated clots, plasma

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Results

Conclusion