Search

Abstract This study is about the quantification and validation of BDNF levels in mouse serum and plasma using a sensitive immunoassay. While BDNF levels are readily detectable in human serum, the functional implications of these measurements are unclear as BDNF released from human blood platelets is the main contributor to the serum levels of BDNF. As mouse platelets do not contain BDNF, this confounding factor is absent in the mouse. Accordingly, BDNF levels in mouse serum and plasma were found to be indistinguishable at 9.92 ± 1.97 pg/mL for serum and 10.58 ± 2.43 pg/mL for plasma (p = 0.473). These levels are approximately a thousand times lower than those measured in human serum and pre-adsorption with anti-BDNF, but not with anti-NGF or anti-NT3 monoclonal antibodies, markedly reduced the BDNF signal. These results open the possibility to explore the relevance of BDNF levels as a biomarker in accessible body fluids using existing mouse models mimicking human pathological conditions.

This review focuses on neurotrophins and their tyrosine kinase receptors, with an emphasis on their relevance to the function and dysfunction in the human nervous system. It also deals with measurements of BDNF levels and highlights recent findings from our laboratory on TrkB and TrkC signalling in human neurons. These include ligand selectivity and Trk activation by neurotrophins and non-neurotrophin ligands. The ligand-induced down-regulation and re-activation of Trk receptors is also discussed.

Abstract Background Rett syndrome (RS) is a severe neurodevelopmental disorder for which there is no approved therapy. This study aimed to assess safety and efficacy of oral fingolimod in children with RS using a pre-post and case–control design. Methods At the University of Basel Children’s Hospital, Basel, Switzerland, children with RS were included if they were older than 6 years and met the established diagnostic criteria of RS, including a positive MeCP2 mutation. Participants were observed 6 months before and after treatment and received 12 months of fingolimod treatment. Serum samples of 50 children without RS served as reference for brain-derived neurotrophic factor (BDNF) measurements. Primary outcome measures were safety and efficacy, the latter measured by change in levels of BDNF in serum/CSF (cerebrospinal fluid) and change in deep gray matter volumes measured by magnetic resonance imaging (MRI). Secondary outcome measure was efficacy measured by change in clinical scores [Vineland Adaptive Behaviour Scale (VABS), Rett Severity Scale (RSSS) and Hand Apraxia Scale (HAS)]. Results Six children with RS (all girls, mean and SD age 11.3 ± 3.1 years) were included. Serum samples of 50 children without RS (25 females, mean and SD age 13.5 ± 3.9 years) served as reference for BDNF measurements. No serious adverse events occurred. Primary and secondary outcome measures were not met. CSF BDNF levels were associated with all clinical scores: RSSS (estimate − 0.04, mult.effect 0.96, CI [0.94; 0.98], p = 0.03), HAS (estimate − 0.09, mult.effect 0.91, CI [0.89; 0.94], p < 0.01) and VABS (communication: estimate 0.03, mult.effect 1.03, CI [1.02; 1.04], p

Abstract Brain-derived neurotrophic factor (BDNF) plays crucial roles in brain function. Numerous studies report alterations in BDNF levels in human serum in various neurological conditions, including mood disorders such as depression. However, little is known about BDNF levels in the blood during pregnancy. We asked whether maternal depression and/or anxiety during pregnancy were associated with altered serum BDNF levels in mothers (n = 251) and their new-born infants (n = 212). As prenatal exposure to maternal mood disorders significantly increases the risk of neurological conditions in later life, we also examined the possibility of placental BDNF transfer by developing a new mouse model. We found no association between maternal symptoms of depression and either maternal or infant cord blood serum BDNF. However, maternal symptoms of anxiety correlated with significantly raised maternal serum BDNF exclusively in mothers of boys (r = 0.281; P = 0.005; n = 99). Serum BDNF was significantly lower in male infants than female infants but neither correlated with maternal anxiety symptoms. Consistent with this observation, we found no evidence for BDNF transfer across the placenta. We conclude that the placenta protects the developing fetus from maternal changes in serum BDNF that could otherwise have adverse consequences for fetal development.

Abstract Objective To determine the levels of brain‐derived neurotrophic factor (BDNF) in the serum of patients suffering from multiple sclerosis (MS) to evaluate the potential of serum BDNF as a biomarker for MS. Methods Using a recently validated enzyme‐linked immunoassay (ELISA) we measured BDNF in patients with MS (pwMS), diagnosed according to the 2001 McDonald criteria and aged between 18 and 70 years, participating in a long‐term cohort study with annual clinical visits, including blood sampling, neuropsychological testing, and brain magnetic resonance imaging (MRI). The results were compared with an age‐ and sex‐matched cohort of healthy controls (HC). Correlations between BDNF levels and a range of clinical and magnetic resonance imaging variables were assessed using an adjusted linear model. Results In total, 259 pwMS and 259 HC were included, with a mean age of 44.42 ± 11.06 and 44.31 ± 11.26 years respectively. Eleven had a clinically isolated syndrome (CIS), 178 relapsing remitting MS (RRMS), 56 secondary progressive MS (SPMS), and 14 primary progressive MS (PPMS). Compared with controls, mean BDNF levels were lower by 8 % (p˂0.001) in pwMS. The level of BDNF in patients with SPMS was lower than in RRMS (p = 0.004). Interpretation We conclude that while the use of comparatively large cohorts enables the detection of a significant difference in BDNF levels between pwMS and HC, the difference is small and unlikely to usefully inform decision‐making processes at an individual patient level.

Background Hitherto, BDNF levels in humans have been primarily measured in serum and/or plasma where these levels are readily measurable, but primarily reflect the content of BDNF in blood platelets. By contrast, previous attempts to measure BDNF levels in readily accessible human body fluids such as saliva have been complicated by a lack of sensitivity and/or specificity of BDNF ELISAs (see Discussion). Recently, the suitability of a highly sensitive BDNF ELISA assay was validated using mouse plasma and serum where conventional BDNF ELISA fail to detect BDNF. In this report, we demonstrate that BDNF levels in human saliva are extremely low, in the low pg/mL range, yet detectable in all saliva samples tested. Methods Saliva samples were collected from healthy volunteers by a passive drool method. All samples were aliquoted and immediately frozen to keep at -80°C until use. At the time of use, the samples were thawed, centrifuged to remove any remaining particles and BDNF measurement conducted by using a previously validated BDNF ELISA assay (see below). Recombinant mature BDNF was used as a reference. Results The intra-assay variability was in the range of CV = 1.8 to 4.9%. Saliva samples could be kept frozen at -80°C for 2 months until use for measurements, but more than 4 freeze and thaw cycles caused BDNF losses presumably due to structural change of the antigen. The measurements were not affected by the method of collection provided the samples were diluted at least 2-fold. Conclusions The results indicate that human saliva samples collected in a non-invasive fashion can be used as a source of material to try and correlate BDNF levels with human conditions of interest. These results also confirm those of an independent study published recently using the same BDNF ELISA kit to measure BDNF levels in human saliva samples.