The impact of age, weight and gender on BDNF levels in human platelets and plasma
Introduction
Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, is a homodimeric protein that has been highly conserved in structure and function during evolution [14], [29]. It is well established that BDNF serves as a target-derived survival and differentiation factor for neuronal subpopulations in prenatal stages [62]. In the adult nervous system, BDNF plays a predominantly functional role. Both long- and short-term effects have been described [37]. On one hand, BDNF acts as a potent excitatory neurotransmitter leading to rapid depolarization of postsynaptic neurons, even at very low concentrations [17], [21]. On the other hand, BDNF induces long-lasting changes in synaptic plasticity, neurotransmitter and neuropeptide production and excitability [6], [22], [30], [38], [68]. Long-term effects of BDNF are thought to play a key role in learning, memory and behavior [11], [16]. There is accumulating evidence for a functional role of BDNF in the periphery, too. BDNF modulates neuronal function in specific subpopulations of the peripheral nervous system [31]. In addition, there is recent evidence that BDNF can act on specific non-neuronal cells in the periphery, such as activated eosinophils [43].
Altered BDNF production and secretion has been shown in a variety of diseases. Neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease are associated with decreased BDNF levels in the brain [8], [19], [28], [39], [49], [51]. A variety of studies has postulated that depression is characterized by decreased BDNF production, too [1], [7], [60]. In contrast, inflammatory diseases such as multiple sclerosis are associated with enhanced BDNF synthesis in inflamed tissues [4], [25], [66]. In these diseases, it has been postulated that BDNF might protect neurons from inflammatory damage [18]. The abundance of BDNF in inflamed tissues, however, can lead to neuronal hyperreactivity. This hyperreactivity contributes to clinical symptoms such as postinflammatory pain [15], [34]. Recently, we have shown that enhanced local BDNF production in the lung contributes to neuronal hyperreactivity and pathologic bronchoconstriction in asthma [5], [32].
First evidence for the presence of BDNF in human plasma and serum emerged a decade ago [58]. Strikingly, average serum levels of BDNF were more than 100-fold higher than plasma levels [55]. This difference is due to the degranulation of platelets during the clotting process [12]. Human platelets contain large amounts of BDNF protein [12], [53], [71]. It has been elegantly demonstrated that the amount of BDNF in serum is nearly identical to the amount of BDNF found in washed platelet lysates [12]. Thus, the difference between serum and plasma BDNF levels seems to reflect the amount of BDNF stored in circulating platelets. Notably, platelet BDNF has been postulated not to originate from megakaryocyte precursor cells. It seems to be acquired from plasma and other compartments by internalization through as yet unidentified binding sites [12]. The cellular sources of BDNF found in human plasma are not clearly defined yet. Potential sources are vascular endothelial and smooth muscle cells [10], [31], [41]. Activated macrophages or lymphocytes could represent additional sources of BDNF [4], [13], [25]. Since BDNF is known to cross the blood–brain barrier in both directions, a substantial part of circulating BDNF might originate from neurons and glia cells of the central nervous system [24], [48], [52].
There are several studies reporting serum BDNF levels in healthy human subjects. In most cases, these subjects represent controls in studies evaluating the impact of diseases such as depression or schizophrenia on BDNF in serum [23], [45], [60], [63]. The numbers of examined healthy volunteers in these studies were relatively small, precluding any evaluation of age or gender influences on BDNF serum levels in a statistically relevant manner. In addition, there is only little published data on BDNF levels in human plasma. Thus, information about the influence of age or physical parameters on BDNF levels in human serum, platelets or plasma is still lacking. We have, therefore, initiated a prospective and systematic study with a large cohort of human subjects to elucidate the influence of age, weight and gender on BDNF levels in human peripheral blood.
Section snippets
Study design
This prospective study was conducted in Rostock (Germany) from September to December 2002. Healthy volunteers between 20 and 60 years of age were included. The study was approved by the ethics committee of the Medical Faculty of the University of Rostock. Prior to enrollment, participating subjects gave their written informed consent and were asked to answer a questionnaire regarding age, weight, height, chronic diseases, current illnesses, regular medication, the appearance of allergies or a
General results
There was a wide range of BDNF concentrations in human serum, platelets and plasma (Table 1). To some extent, BDNF levels in plasma correlated with BDNF levels in platelets (r=0.22, P<0.05). Correlating BDNF with other mediators stored in platelets, we found a stronger correlation of serum BDNF levels with serum TGF-β1 levels (r=0.75, P<0.01) than with serum serotonin (5-HT) levels (r=0.31, P<0.05) (Fig. 1). In order to emphasize the specific platelet BDNF content of each individual, we have
Discussion
It was the aim of this study to elucidate the influence of age, gender and physical parameters on BDNF levels in human peripheral blood. Variance and median levels of BDNF in serum and platelets were in keeping with data published recently by Fujimura et al. (n=11 adults) [12]. Other studies (n=number of examined healthy adults) reported serum levels of 26.5±7 ng BDNF/ml (n=30) [23], 11.4±7.7 ng BDNF/ml (n=35) [63], 17.3±1.6 ng BDNF/ml (n=20) [45], 18.9±5.7 ng BDNF/ml (n=6) [58] and 27.7±11.4 ng BDNF/ml (
Acknowledgements
This work was supported by the Deutsche Forschungsgemeinschaft (DFG).
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