Serum Levels of Mature Brain-Derived Neurotrophic Factor (BDNF) and Its Precursor proBDNF in Healthy Subjects

Abstract

BACKGROUND:Accumulating evidence points to the brain-derived neurotrophic factor (BDNF) as a biomarker for neuropsychiatric diseases, such as major depression. Mature BDNF is synthesized from its precursor form, proBDNF. Although BDNF levels in human blood can be measured using commercially available human BDNF ELISA kits, due to limited specificity of the BDNF antibody, these kits are unable to distinguish between proBDNF and mature BDNF. In this study, we measured serum levels of proBDNF and mature BDNF in healthy subjects, using human proBDNF and BDNF ELISA kits, respectively. METHODS:Serum levels of proBDNF and mature BDNF in healthy subjects (n = 40) were measured using the sandwich human proBDNF and BDNF ELISA kits. RESULTS:In healthy subjects, serum levels of mature BDNF were 23.71 ± 5.61 ng/mL (mean ± S.D., n=40). Serum levels of proBDNF in healthy subjects were 7.58 ± 7.68 ng/mL (mean ± S.D., n=25). However in 15 subjects, serum levels of proBDNF were less than the minimum detectable concentration (0.5 ng/mL) of the kit. CONCLUSIONS:This study shows that serum levels of proBDNF and mature BDNF are measurable using either the commercially available human proBDNF or BDNF ELISA kits, although the sensitivity of proBDNF kit was unacceptably low. These ELISA kits may be useful for measuring proBDNF and mature BDNF in the body fluids of patients with neuropsychiatric, cardiovascular and other diseases.

Activation of the sigma-1 receptor by haloperidol metabolites facilitates brain-derived neurotrophic factor secretion from human astroglia

“…i.e., mature versus proBDNF. The only published reports that we could find with such claims presented no supporting data (Chen et al, 2006; Yoshida et al, 2012). Further, a recent report concerning claims of selectivity used dot blotting, instead of an ELISA approach, for the evaluation (Polacchini et al, 2015).…”

“…Because no published data accompanied literature claims of selectivity for proBDNF versus mature BDNF using a sandwich assay (Chen et al, 2006; Yoshida et al, 2012), we tested the ability of the BDNF Emax ImmunoAssay kit (Promega) to discriminate between proBDNF (precursor) and mature BDNF (processed) under our in situ ELISA conditions. Specifically, we tested high and low concentrations of purified human proBDNF and mature BDNF under identical assay conditions.…”

The Interplay of Stress and Sleep Impacts BDNF Level

“…Both isoforms are considered to transmit important, opposing cellular effects via their appropriate receptors p75 neurotrophin receptor (p75 NTR ) and tropomyosin-related tyrosine kinase receptor B (TrkB). Recently, Yoshida and coworkers could demonstrate the measurement of pro- and mature BDNF from human serum of healthy subjects for the first time [46]. Therefore, it would be beneficial to especially quantify individual levels of pro- and mature BDNF to reveal if reduced levels of total serum BDNF are driven by an imbalance of either pro- or mature BDNF, which was already shown for patients suffering from major depression [47].…”

Brain-derived neurotrophic factor (BDNF) as a potential mechanism of the effects of acute exercise on cognitive performance

“…Assessments of pBDNF isoform proportions in human blood requires the use of Western blot analyses 32,33 or specifically designed enzyme-linked immunosorbent assays (ELISAs). 34,35 Studies exploring the acute exercise-BDNF relationship have typically used ELISA kits that assess pBDNF concentrations without differentiating between isoforms (e.g., those produced by Millipore, Promega), or specify an assessment of mBDNF noting its slight crossreactivity with proBDNF (i.e., those produced by R&D Systems). To our knowledge, no acute exercise study has used ELISA kits that assess pBDNF concentrations of specific isoforms (i.e., those produced by Aviscera).…”