journal article Open Access Sep 19, 2016

Ultra-sensitive detection of brain-derived neurotrophic factor (BDNF) in the brain of freely moving mice using an interdigitated microelectrode (IME) biosensor

View at Publisher Save 10.1038/srep33694
Abstract
AbstractBrain-derived neurotrophic factor (BDNF) plays a critical role in cognitive processes including learning and memory. However, it has been difficult to detect BDNF in the brains of behaving animals because of its extremely low concentration, i.e., at the sub-nanogram/mL level. Here, we developed an interdigitated microelectrode (IME) biosensor coated with an anti-BDNF an anti-BDNF antibody in a polydimethylsiloxane (PDMS)-based microfluidic channel chip. This sensor could detect BDNF from microliter volumes of liquid samples even at femtogram/mL concentrations with high selectivity over other growth factors. Using this biosensor, we examined whether BDNF is detectable from periodical collection of cerebrospinal fluid microdialysate, sampled every 10 min from the hippocampus of mice during the context-dependent fear-conditioning test. We found that the IME biosensor could detect a significant increase in BDNF levels after the memory task. This increase in BDNF levels was prevented by gene silencing of BDNF, indicating that the IME biosensor reliably detected BDNFin vivo. We propose that the IME biosensor provides a general-purpose probe for ultrasensitive detection of biomolecules with low abundance in the brains of behaving animals.
Topics

No keywords indexed for this article. Browse by subject →

References
33
[1]
Bramham, C. R. & Messaoudi, E. BDNF function in adult synaptic plasticity: The synaptic consolidation hypothesis. Prog. Neurobiol. 76, 99–125 (2005). 10.1016/j.pneurobio.2005.06.003
[2]
Lindsay, R. Nerve growth factors (NGF, BDNF) enhance axonal regeneration but are not required for survival of adult sensory neurons. J. Neurosci. 8, 2394–2405 (1988). 10.1523/jneurosci.08-07-02394.1988
[3]
Lohof, A. M., Ip, N. Y. & Poo, M. M. Potentiation of developing neuromuscular synapses by the neurotrophins NT-3 and BDNF. Nature 363, 350–353, 10.1038/363350a0 (1993). 10.1038/363350a0
[4]
Maisonpierre, P. C. et al. NT-3, BDNF, and NGF in the developing rat nervous system: Parallel as well as reciprocal patterns of expression. Neuron 5, 501–509 (1990). 10.1016/0896-6273(90)90089-x
[5]
Yoshii, A. & Constantine-Paton, M. Postsynaptic BDNF-TrkB signaling in synapse maturation, plasticity, and disease. Dev. Neurobiol. 70, 304–322 (2010). 10.1002/dneu.20765
[6]
Autry, A. E. & Monteggia, L. M. Brain-Derived Neurotrophic Factor and Neuropsychiatric Disorders. Pharmacol. Rev. 64, 238–258, 10.1124/pr.111.005108 (2012). 10.1124/pr.111.005108
[7]
Hall, J. R., O’Bryant, S. E., Johnson, L. & Barber, R. C. Depression and brain-derived neurotrophic factor levels in Alzheimer’s disease. Neurosci. Med. 2, 43–47, 10.4236/nm.2011.21006 (2011). 10.4236/nm.2011.21006
[8]
Hosang, G. M., Shiles, C., Tansey, K. E., McGuffin, P. & Uher, R. Interaction between stress and the BDNFVal66Met polymorphism in depression: a systematic review and meta-analysis. BMC Med. 12, 1–11 (2014). 10.1186/1741-7015-12-7
[9]
Shimizu, E. et al. Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants. Biol. Psychiatry 54, 70–75 (2003). 10.1016/s0006-3223(03)00181-1
[10]
Brunoni, A. R., Lopes, M. & Fregni, F. A systematic review and meta-analysis of clinical studies on major depression and BDNF levels: implications for the role of neuroplasticity in depression. Int. J. Neuropsychopharmacol. 11, 1169–1180 (2008). 10.1017/s1461145708009309
[11]
Scalzo, P., Kümmer, A., Bretas, T. L., Cardoso, F. & Teixeira, A. L. Serum levels of brain-derived neurotrophic factor correlate with motor impairment in Parkinson’s disease. J. Neurol. 257, 540–545 (2010). 10.1007/s00415-009-5357-2
[12]
Chen, W. G. et al. Derepression of BDNF transcription involves calcium-dependent phosphorylation of MeCP2. Science 302, 885–889 (2003). 10.1126/science.1086446
[13]
Młyniec, K., Budziszewska, B., Holst, B., Ostachowicz, B. & Nowak, G. GPR39 (zinc receptor) knockout mice exhibit depression-like behavior and CREB/BDNF down-regulation in the hippocampus. Int. J. Neuropsychopharmacol. 18, doi: http://dx.doi.org/10.1093/ijnp/pyu002( 2014). 10.1093/ijnp/pyu002
[14]
Croll, S. D., Ip, N. Y., Lindsay, R. M. & Wiegand, S. J. Expression of BDNF and trkB as a function of age and cognitive performance. Brain Res. 812, 200–208 (1998). 10.1016/s0006-8993(98)00993-7
[15]
Elfving, B., Plougmann, P. H. & Wegener, G. Detection of brain-derived neurotrophic factor (BDNF) in rat blood and brain preparations using ELISA: Pitfalls and solutions. J. Neurosci. Methods 187, 73–77 (2010). 10.1016/j.jneumeth.2009.12.017
[16]
Soya, H. et al. BDNF induction with mild exercise in the rat hippocampus. Biochem. Biophys. Res. Comm. 358, 961–967 (2007). 10.1016/j.bbrc.2007.04.173
[17]
Di Chiara, G. In-vivo brain dialysis of neurotransmitters. Trends Pharmacol. Sci. 11, 116–121 (1990). 10.1016/0165-6147(90)90197-g
[18]
Humpel, C., Ebendal, T. & Olson, L. Microdialysis: a way to study in vivo release of neurotrophic bioactivity: a critical summary. J. Mol. Med. 74, 523–526, 10.1007/BF00204978 (1996). 10.1007/bf00204978
[19]
Gomez-Pinilla, F., Zhuang, Y., Feng, J., Ying, Z. & Fan, G. Exercise impacts brain-derived neurotrophic factor plasticity by engaging mechanisms of epigenetic regulation. Eur. J. Neurosci. 33, 383–390 (2011). 10.1111/j.1460-9568.2010.07508.x
[20]
Millner, P., Caygill, R. & Conroy, D. Impedance interrogated affinity biosensors for medical applications: novel targets and mechanistic studies in Biosensors for medical applications (ed. Higson, S. ) 103–134 (Elsevier, 2012). 10.1533/9780857097187.1.103
[21]
Griffiths, D. J. & College, R. Introduction to electrodynamics. Vol. 3 (Prentice Hall Upper Saddle River, NJ, 1999).
[22]
Chen, Z.-Y. et al. Genetic variant BDNF (Val66Met) polymorphism alters anxiety-related behavior. Science 314, 140–143 (2006). 10.1126/science.1129663
[23]
Morrissey, C. et al. Effect of artemisinin derivatives on apoptosis and cell cycle in prostate cancer cells. Anticancer Drugs 21, 423–432, 10.1097/CAD.0b013e328336f57b (2010). 10.1097/cad.0b013e328336f57b
[24]
Barber, A. G. et al. Characterization of desmoglein expression in the normal prostatic gland. Desmoglein 2 is an independent prognostic factor for aggressive prostate cancer. PLoS One 9, e98786, 10.1371/journal.pone.0098786 (2014). 10.1371/journal.pone.0098786
[25]
Liu, I. Y. C., Lyons, W. E., Mamounas, L. A. & Thompson, R. F. Brain-derived neurotrophic factor plays a critical role in ontextual fear conditioning. J. Neurosci. 24, 7958–7963 (2004). 10.1523/jneurosci.1948-04.2004
[26]
Panja, D. & Bramham, C. R. BDNF mechanisms in late LTP formation: A synthesis and breakdown. Neuropharmacology 76, Part C, 664–676 (2014). 10.1016/j.neuropharm.2013.06.024
[27]
Tanaka, J.-i. et al. Protein synthesis and neurotrophin-dependent structural plasticity of single dendritic spines. Science 319, 1683–1687 (2008). 10.1126/science.1152864
[28]
Radka, S. F., Holst, P. A., Fritsche, M. & Altar, C. A. Presence of brain-derived neurotrophic factor in brain and human and rat but not mouse serum detected by a sensitive and specific immunoassay. Brain Res. 709, 122–301 (1996). 10.1016/0006-8993(95)01321-0
[29]
Angelucci, F., Aloe, L., Vasquez, P. J. & Mathe, A. A. Mapping the differences in the brain concentration of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in an animal model of depression. Neuroreport 11, 1369–1373 (2000). 10.1097/00001756-200004270-00044
[30]
Angelucci, F., Aloe, L., Jimenez-Vasquez, P. & Mathe, A. A. Lithium treatment alters brain concentrations of nerve growth factor, brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor in a rat model of depression. Int. J. Neuropsychopharmacol. 6, 225–231,10.1017/S1461145703003468 (2003). 10.1017/s1461145703003468
[31]
Altar, C. A., Whitehead, R. E., Chen, R., Wortwein, G. & Madsen, T. M. Effects of electroconvulsive seizures and antidepressant drugs on brain-derived neurotrophic factor protein in rat brain. Biol Psychiatry 54, 703–709 (2003). 10.1016/s0006-3223(03)00073-8
[32]
Jacobsen, J. P. & Mork, A. The effect of escitalopram, desipramine, electroconvulsive seizures and lithium on brain-derived neurotrophic factor mRNA and protein expression in the rat brain and the correlation to 5-HT and 5-HIAA levels. Brain Res. 1024, 183–192, 10.1016/j.brainres.2004.07.065 (2004). 10.1016/j.brainres.2004.07.065
[33]
Szapacs, M. E. et al. Exploring the relationship between serotonin and brain-derived neurotrophic factor: analysis of BDNF protein and extraneuronal 5-HT in mice with reduced serotonin transporter or BDNF expression. J Neurosci. Methods 140, 81–92, 10.1016/j.jneumeth.2004.03.026 (2004). 10.1016/j.jneumeth.2004.03.026
Metrics
33
Citations
33
References
Details
Published
Sep 19, 2016
Vol/Issue
6(1)
License
View
Cite This Article
Yong Kyoung Yoo, Jaekwang Lee, Gangeun Kim, et al. (2016). Ultra-sensitive detection of brain-derived neurotrophic factor (BDNF) in the brain of freely moving mice using an interdigitated microelectrode (IME) biosensor. Scientific Reports, 6(1). https://doi.org/10.1038/srep33694