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.
References
[1]
Smith MA, Makino S, Kvetnansky R, Post RM (1995) Stress and glucocorticoids affect the expression of brain-derived neurotrophic factor and neurotrophin-3 mRNAs in the hippocampus. J Neurosci 15: 1768–1777.
[2]
Nibuya M, Morinobu S, Duman RS (1995) Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments. J Neurosci 15, 7539–7547.
[3]
Lommatzsch M, Zingler D, Schuhbaeck K, Schloetcke K, Zingler C, et al. (2005) The impact of age, weight and gender on BDNF levels in human platelets and plasma. Neurobiol Aging 26: 115–123. doi: 10.1016/j.neurobiolaging.2004.03.002
[4]
Marano CM, Phatak P, Vemulapalli UR, Sasan A, Nalbandyan MR, et al. (2007) Increased plasma concentration of brain-derived neurotrophic factor with electroconvulsive therapy: a pilot study in patients with major depression. J Clin Psychiatry 68: 512–517. doi: 10.4088/jcp.v68n0404
[5]
Pan W, Banks WA, Fasold MB, Bluth J, Kastin AJ (1998) Transport of brain-derived neurotrophic factor across the blood-brain barrier. Neuropharmacology 37: 1553–1561. doi: 10.1016/s0028-3908(98)00141-5
[6]
Kim YK, Lee HP, Won SD, Park EY, Lee HY, et al. (2007) Low plasma BDNF is associated with suicidal behavior in major depression. Prog Neuropsychopharmacol Biol Psychiatry 31: 78–85. doi: 10.1016/j.pnpbp.2006.06.024
[7]
Okuno K, Yoshimura R, Ueda N, Ikenouchi-Sugita A, Umene-Nakano W, et al. (2011) Relationships between stress, social adaptation, personality traits, brain-derived neurotrophic factor and 3-methoxy-4-hydroxyphenylglycol plasma concentrations in employees at a publishing company in Japan. Psychiatry Res 186: 326–332. doi: 10.1016/j.psychres.2010.07.023
[8]
Karege F, Bondolfi G, Gervasoni N, Schwald M, Aubry JM, et al. (2005) Low brain-derived neurotrophic factor (BDNF) levels in serum of depressed patients probably results from lowered platelet BDNF release unrelated to platelet reactivity. Biol Psychiatry 57: 1068–1072. doi: 10.1016/j.biopsych.2005.01.008
[9]
Elzinga BM, Molendijk ML, Oude Voshaar RC, Bus BA, Prickaerts J, et al. (2011) The impact of childhood abuse and recent stress on serum brain-derived neurotrophic factor and the moderating role of BDNF Val66Met. Psychopharmacology (Berl) 214: 319–328. doi: 10.1007/s00213-010-1961-1
[10]
Neeper SA, Gómez-Pinilla F, Choi J, Cotman C (1995) Exercise and brain neurotrophins. Nature 373: 109. doi: 10.1038/373109a0
[11]
Zoladz JA, Pilc A, Majerczak J, Grandys M, Zapart-Bukowska J, et al. (2008) Endurance training increases plasma brain-derived neurotrophic factor concentration in young healthy men. J Physiol Pharmacol 59 Suppl 7119–132. doi: 10.1055/s-0029-1202340
[12]
Baker LD, Frank LL, Foster-Schubert K, Green PS, Wilkinson CW, et al. (2010) Effects of aerobic exercise on mild cognitive impairment: a controlled trial. Arch Neurol 67: 71–79. doi: 10.1001/archneurol.2009.307
[13]
Gorgulu Y, Caliyurt O (2009) Rapid antidepressant effects of sleep deprivation therapy correlates with serum BDNF changes in major depression. Brain Res Bull 80: 158–162. doi: 10.1016/j.brainresbull.2009.06.016
[14]
Ibrahim L, Duncan W, Luckenbaugh DA, Yuan P, Machado-Vieira R, et al. (2011) Rapid antidepressant changes with sleep deprivation in major depressive disorder are associated with changes in vascular endothelial growth factor (VEGF): a pilot study. Brain Res Bull 86: 129–133. doi: 10.1016/j.brainresbull.2011.06.003
[15]
Kotan Z, Sarand？l E, K？rhan E, Ozkaya G, K？rl？ S (2012) Serum brain-derived neurotrophic factor, vascular endothelial growth factor and leptin levels in patients with a diagnosis of severe major depressive disorder with melancholic features. Ther Adv Psychopharmacol 2: 65–74. doi: 10.1177/2045125312436572
[16]
Takebayashi M, Hashimoto R, Hisaoka K, Tsuchioka M, Kunugi H (2010) Plasma levels of vascular endothelial growth factor and fibroblast growth factor 2 in patients with major depressive disorders. J Neural Transm 117: 1119–1122. doi: 10.1007/s00702-010-0452-1
[17]
Ventriglia M, Zanardini R, Pedrini L, Placentino A, Nielsen MG, et al. (2009) VEGF serum levels in depressed patients during SSRI antidepressant treatment. Prog Neuropsychopharmacol Biol Psychiatry 33: 146–149. doi: 10.1016/j.pnpbp.2008.11.009
[18]
Fornaro M, Rocchi G, Escelsior A, Contini P, Ghio M, et al.. (2013) VEGF plasma level variations in duloxetine-treated patients with major depression. J Affect Disord. in press.
[19]
Sun FY, Guo X (2005) Molecular and cellular mechanisms of neuroprotection by vascular endothelial growth factor. J Neurosci Res 79: 180–184. doi: 10.1002/jnr.20321
[20]
Warner-Schmidt JL, Duman RS (2008) VEGF as a potential target for therapeutic intervention in depression. Curr Opin Pharmacol 8: 14–19. doi: 10.1016/j.coph.2007.10.013
[21]
Warner-Schmidt JL, Duman RS (2007) VEGF is an essential mediator of the neurogenic and behavioral actions of antidepressants. Proc Natl Acad Sci U S A 104: 4647–4652. doi: 10.1073/pnas.0610282104
[22]
Aitken RC (1969) Measurement of feelings using visual analogue scales. Proc R Soc Med 62: 989–993.
[23]
Kamata N, Tanaka K, Morita S, Tagaya H, Kawashima M, et al. (2011) Relationship between autonomic nervous system activity during sleep and fasting glucose in Japanese workers. Ind Health 49: 427–433. doi: 10.2486/indhealth.ms1257
Sadeh A, Sharkey KM, Carskadon MA (1994) Activity-based sleep-wake identification: an empirical test of methodological issues. Sleep 17: 201–207.
[26]
Baharav A, Kotagal S, Gibbons V, Rubin BK, Pratt G, et al. (1995) Fluctuations in autonomic nervous activity during sleep displayed by power spectrum analysis of heart rate variability. Neurology 45: 1183–1187. doi: 10.1212/wnl.45.6.1183
[27]
Lee BH, Kim H, Park SH, Kim YK (2007) Decreased plasma BDNF level in depressive patients. J Affect Disord 101: 239–244. doi: 10.1016/j.jad.2006.11.005
[28]
Pillai A, Kale A, Joshi S, Naphade N, Raju MS, et al. (2010) Decreased BDNF levels in CSF of drug-naive first-episode psychotic subjects: correlation with plasma BDNF and psychopathology. Int J Neuropsychopharmacol 13: 535–539. doi: 10.1017/s1461145709991015
[29]
Karege F, Perret G, Bondolfi G, Schwald M, Bertschy G, et al. (2002) Decreased serum brain-derived neurotrophic factor levels in major depressed patients. Psychiatry Res 109: 143–148. doi: 10.1016/s0165-1781(02)00005-7
[30]
Mitoma M, Yoshimura R, Sugita A, Umene W, Hori H, et al. (2008) Stress at work alters serum brain-derived neurotrophic factor (BDNF) levels and plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) levels in healthy volunteers: BDNF and MHPG as possible biological markers of mental stress? Prog Neuropsychopharmacol Biol Psychiatry 32: 679–685. doi: 10.1016/j.pnpbp.2007.11.011
[31]
Halmai Z, Dome P, Dobos J, Gonda X, Szekely A, et al. (2013) Peripheral vascular endothelial growth factor level is associated with antidepressant treatment response: results of a preliminary study. J Affect Disord 144: 269–273. doi: 10.1016/j.jad.2012.09.006
[32]
Dome P, Halmai Z, Dobos J, Lazary J, Gonda X, et al. (2012) Investigation of circulating endothelial progenitor cells and angiogenic and inflammatory cytokines during recovery from an episode of major depression. J Affect Disord 136: 1159–1163. doi: 10.1016/j.jad.2011.09.027
[33]
Heine VM, Zareno J, Maslam S, Jo？ls M, Lucassen PJ (2005) Chronic stress in the adult dentate gyrus reduces cell proliferation near the vasculature and VEGF and Flk-1 protein expression. Eur J Neurosci 21: 1304–1314. doi: 10.1111/j.1460-9568.2005.03951.x
[34]
Newton SS, Collier EF, Hunsberger J, Adams D, Terwilliger R, et al. (2003) Gene profile of electroconvulsive seizures: induction of neurotrophic and angiogenic factors. J Neurosci 23: 10841–10851.
[35]
Greene J, Banasr M, Lee B, Warner-Schmidt J, Duman RS (2009) Vascular endothelial growth factor signaling is required for the behavioral actions of antidepressant treatment: pharmacological and cellular characterization. Neuropsychopharmacology 34: 2459–2468. doi: 10.1038/npp.2009.68
[36]
Chen TC, Hsieh SS (2001) Effects of a 7-day eccentric training period on muscle damage and inflammation. Med Sci Sports Exerc 33: 1732–1738. doi: 10.1097/00005768-200110000-00018
[37]
Lang H, Würzburg U (1982) Creatine kinase, an enzyme of many forms. Clin Chem 28: 1439–1447.
[38]
Schimke RT (1973) Control of enzyme levels in mammalian tissues. Adv Enzymol Relat Areas Mol Biol 37: 135–187.
[39]
Tang SW, Chu E, Hui T, Helmeste D, Law C (2008) Influence of exercise on serum brain-derived neurotrophic factor concentrations in healthy human subjects. Neurosci Lett 431: 62–65. doi: 10.1016/j.neulet.2007.11.019
[40]
Suzuki T, Ouchi K, Kameyama K, Takahashi M (2009) Development of a sleep monitoring system with wearable vital sensor for home use. BIODEVICES, 326–331. Available: http://www.itc-ltd.co.jp/pdf/BIODEVICES_？2009_124.pdf?. Accessed 2013 Oct 7.
