BDNF ELISA Kit

Brain-derived neurotrophic factor (BDNF), which belongs to the nerve growth factor (NGF) family, is involved in neurogenesis, neuroprotection, synaptogenesis, etc. and is considered as a candidate marker for psychiatric diseases, including depression and autism. Its association has been reported with cardiac disease, diabetes, gout, periodontal disease, stress, exercise, etc. in addition to neurology, which makes it as a target of research in a wide range of areas. The precursor of BDNF is proBDNF, part of which is cleaved to form mature BDNF (mBDNF). proBDNF has been reported to bind to the p75NTR receptor in vivo, showing a different action from that of mBDNF.

Review: BDNF and psychiatric diseases -a new research strategy by quantitative analysis of mature BDNF-

BDNF is a molecule that plays an important role in the development and maintenance of nerve function. In recent years, its involvement in various diseases has been reported, leading to growing expectations for its use as a biomarker. proBDNF, the precursor of BDNF, is processed to yield mature BDNF (mBDNF). Since proBDNF and mBDNF show completely different effects, there is a need for a method that can accurately measure mBDNF.

BDNF

BDNF is a secretory protein, which was isolated from porcine brains by Barde et al. in 1982 as one of neurotrophic factors highly expressed in the brain. BDNF is the second neurotrophic factor identified in the neurotrophin family and is widely distributed in the brain during the development to maturation stage of the nerve system. Its representative known effects include promotion of survival of nerve cells and formation of synapses through a high-affinity receptor, Tropomyosin related kinase B (TrkB).1), 2) As explained above, BDNF is an important factor contributing to the formation and maintenance of nerve function, attracting a lot of attention in neuroscience.

Expectation for biomarkers

It has been suggested that BDNF is deeply involved in diseases caused in the brain, such as psychiatric diseases.3) In depression in particular, its use as a biomarker has been expected since the first report by Karege et al. that the serum BDNF level in patients with depression is lower than that in healthy individuals.4) The BDNF level is decreased especially in patients with depression not on antidepressants, suggesting the potential of quantitative analysis of BDNF as an indicator of depression treatment. Some recent meta-analyses have also suggested decreased serum BDNF in patients with bipolar disorder or schizophrenia in addition to depression.5) Overall, BDNF is likely to be a key factor for various psychiatric diseases, although its characteristic changes in particular psychiatric diseases are currently unknown.

Mature BDNF, precursor BDNF

BDNF is expressed as precursor BDNF (proBDNF), transported to the site of secretion, and processed to yield mature BDNF (mBDNF) 6) (Figure 1). It was previously considered that the precursor, proBDNF, had no physiological function, but it has been recently revealed that it has a completely different physiological function from that of mBDNF. mBDNF induces long-term potentiation (LTP) through TrkB to promote neurogenesis and neurodevelopment. On the other hand, proBDNF induces long-term depression (LTD) through a low-affinity receptor, p75NTR, to promote nerve apoptosis7) (Figure 2). This change in the effect due to the difference in processing suggests the presence of a highly complicated control mechanism of BDNF on the nerve system. Therefore, a method to accurately measure mBDNF is necessary to reveal the mechanisms of various psychiatric diseases.

01897_img06.png

Figure1. Structures of proBDNF and mBDNF
The N-terminal side of proBDNF is cleaved to form mature BDNF.

 

01897_img07.png

Figure2. Effects of proBDNF and mBDNF
proBDNF induces apoptosis and suppression of neurite growth through p75NTR,
whereas mBDNF induces synapse and neurite growth through TrkB.

 

Development of Mature BDNF detection technology

Since mBDNF has no specific sequence to proBDNF (Figure 1), mBDNF-specific detection is very difficult. To address this challenge, we developed Mature BDNF ELISA Kit Wako (product code: 296-83201) and Mature BDNF ELISA Kit Wako, High Sensitive (product code: 298-83901) as ELISA kits using an antibody with high specificity and detection sensitivity having an epitope on the N-terminal side of mBDNF (Figure 3, Table 1). The antibody used in these products has very low cross-reactivity with proBDNF, allowing specific and sensitive detection of mBDNF. The mBDNF levels of serum samples from female patients with major depression, manic depression, or schizophrenia tended to be lower than those in healthy individuals (Table 2). We also succeeded in the measurement of mBDNF in serum and plasma from wild-type and autism model mice using Mature BDNF ELISA Kit Wako, High Sensitive (Table 3). Based on the above results, this detection technology for mature BDNF that we have developed is expected to become a powerful tool in psychiatry.

01897_img08.png

Figure 3. Principle of Mature BDNF ELISA Kit Wako
We succeeded in the development of ELISA kits that can specifically detect mature BDNF
using an antibody recognizing the N-terminal side of mature BDNF.

 

Table 1. Differences between "Mature BDNF ELISA Kit Wako" and "Mature BDNF ELISA Kit Wako, High Sensitive"

Products Mature BDNF ELISA Kit Wako, High Sensitive Mature BDNF ELISA Kit Wako
Code No. 298-83901 296-83201
Standard curve range 0.205 - 50 pg/mL 4.1 - 1,000 pg/mL
Specificity mBDNF mBDNF
Cross-reactivity to human proBDNF <0.5% Approx. 10%
Sample Mouse serum and plasma Rat serum and plasma Human serum and plasma
Sample volume 13 μL Serum: 10μL
Plasma: 5μL
Assay time 4 hours 4 hours
Detection method Luminescent method Colorimetric method

 

Table 2. Measured values of mature BDNF in serum from patients with major depression, patients with manic depression, patients with schizophrenia, and healthy individuals
(Mature BDNF ELISA Kit Wako, product code 296-83201)

  • Healthy Control (n=6)
    No. Sex Age Assay value
    (ng/mL)
    1 F 48 14.5
    2 F 50 22.8
    3 F 54 20
    4 F 47 18.5
    5 F 42 13.8
    6 F 60 19.1
  • Major depression (n=6)
    No. Sex Age Assay value
    (ng/mL)
    1 F 66 15.7
    2 F 38 18.1
    3 F 43 10
    4 F 52 16.6
    5 F 41 22.3
    6 F 58 15.1
  • Bipolar disorder (n=4)
    No. Sex Age Assay value
    (ng/mL)
    1 F 46 16.5
    2 F 52 20.9
    3 F 52 11.5
    4 F 52 11.5
  • Schizophrenia (n=4)
    No. Sex Age Assay value
    (ng/mL)
    1 F 36 17.9
    2 F 53 23.0
    3 F 55 14.6
    4 F 51 10.8
Healthy Control Major depression Bipolar disorder Schizophrenia
18.1±3.41 16.3±4.02 15.1±4.53 16.6±5.17

(ng/mL)

 

Table 3. Measurement of mature BDNF in serum and plasma from autism model mice and wild-type mice
(Mature BDNF ELISA Kit Wako, High Sensitive, product code 298-83901)

Sample Mouse Sample No. Measured (pg/mL)
Serum BTBR mouse*
(autism model mouse)
BTBR-1 12.4
BTBR-2 18.1
BTBR-3 16.1
C57BL/6J
(wild type mouse)
B6J-1 6.96
B6J-2 9.80
B6J-3 9.01
Plasma
(heparin)
BTBR mouse*
(autism model mouse)
BTBR-4 11.1
BTBR-5 9.73
C57BL/6J
(wild type mouse)
B6J-4 6.93
B6J-5 11.6

*BTBR T + Itpr3tf/J mouse

 

Conclusion

The number of patients with psychiatric diseases is continuously increasing worldwide, and scientists are still actively engaged in research on psychiatric diseases. In this area, BDNF, which was introduced above, has been suggested to be involved in various diseases and is attracting growing attention. Our new products, "Mature BDNF ELISA Kit Wako" and "Mature BDNF ELISA Kit Wako, High Sensitive," are completely new mBDNF detection technologies that combine very high specificity and detection sensitivity, and may contribute to the area of psychiatry, which will become more active in the future, as a useful technology for the detection of mBDNF.

References

  1. Schinder, A. F., and Poo, M. M.: Trends in neurosciences, 23(12), 639(2000).
  2. Huang, E. J., and Reichardt, L. F.: Annual review of neuroscience, 24(1), 677(2001).
  3. Hempstead, B. L.: Transactions of the American Clinical and Climatological Association, 126, 9(2015).
  4. Karege, F., et al.: Psychiatry research, 109(2), 143(2002).
  5. Cattaneo, A., et al.: Translational psychiatry, 6(11), e958(2016).
  6. Leßmann, V., and Brigadski, T.: Neuroscience research, 65(1), 11(2009).
  7. Barker, P. A.: Nature neuroscience, 12(2), 105(2009).

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