Acute normobaric hypoxia does not affect the simultaneous exercise-induced increase in circulating BDNF and GDNF in young healthy men: A feasibility study.

Zofia Piotrowicz,Małgorzata Chalimoniuk,Miłosz Czuba,Kamila Płoszczyca K,Józef Langfort,Laurent Mourot

doi:10.1371/journal.pone.0224207

Abstract

Physical exercise has a neuromodulatory effect on the central nervous system (CNS) partially by modifying expression of neuropeptides produced and secreted by neurons and glial cells, among which the best examined are brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF). Because both neurotrophins can cross the brain-blood barrier (BBB), their blood levels indirectly reflect their production in the CNS. Moreover, both neuropeptides are involved in modulation of dopaminergic and serotoninergic system function. Because limited information is available on the effects of exercise to volition exhaustion and acute hypoxia on CNS, BDNF and GDNF formation, the aims of the present study were to verify whether 1) acute exercise to exhaustion in addition to neurons also activates glial cells and 2) additional exposure to acute normobaric moderate hypoxia affects their function. In this feasibility study we measured blood concentrations of BDNF, GDNF, and neuropeptides considered as biomarkers of brain damage (bFGF, NGF, S100B, GFAP) in seven sedentary healthy young men who performed a graded exercise test to volitional exhaustion on a cycle ergometer under normoxic (N) and hypoxic conditions: 2,000 m (H2; FiO2 = 16.6%) and 3,000 m altitude (H3; FiO2 = 14.7%). In all conditions serum concentrations of both BDNF and GDNF increased immediately after cessation of exercise (p<0.01). There was no effect of condition or interaction (condition x time of measurement) and exercise on any of the brain damage biomarkers: bFGF, NGF, S100B, GFAP. Moreover, in N (0<0.01) and H3 (p<0.05) exercise caused elevated serum 5-HT concentration. The results suggest that a graded effort to volitional exhaustion in normoxia, as well as hypoxia, simultaneously activates both neurons and astrocytes. Considering that s100B, GFAP, bFGF, and NGF (produced mainly by astrocytes) are markers of brain damage, it can be assumed that a maximum effort in both conditions is safe for the CNS.

Highlights

Physical effort stimulates many processes in the central nervous system (CNS), among which the best recognized are neurogenesis, brain synaptogenesis, synthesis and use of neurotransmitters, angiogenesis and increase of the blood flow in several cortical and subcortical areas [1,2,3,4,5,6]
Brain-derived neurotrophic factor (BDNF) is the best studied in terms of its effect on the CNS, whereas glial cell line-derived neurotrophic factor (GDNF) is another neurotrophin that is the subject of the latest research
In agreement with the supposition that the latter phenomenon occurred in our study during subjects’ exposure to normobaric hypoxia, we examined the state of the brain by means of measurement of selected neurotrophins which have been considered as markers of CNS damage, i.e. basic fibroblast growth factor (bFGF), calcium binding protein B (S100B), glial fibrillary acidic protein (GFAP) and nerve growth factor (NGF) [95,96,97]

Summary

Introduction

Physical effort stimulates many processes in the central nervous system (CNS), among which the best recognized are neurogenesis, brain synaptogenesis, synthesis and use of neurotransmitters, angiogenesis and increase of the blood flow in several cortical and subcortical areas [1,2,3,4,5,6]. Brain-derived neurotrophic factor (BDNF) is the best studied in terms of its effect on the CNS, whereas glial cell line-derived neurotrophic factor (GDNF) is another neurotrophin that is the subject of the latest research. It was shown that GDNF-induced increases in DA function are associated with a sustained increase in tyrosine hydroxylase (TH) phosphorylation at Ser, which may be maintained for at least one month following its single striatal administration [18]. These results obtained on animals provide a support for the protective neurobiological influence of GDNF against motor deficits

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