title: Ultra-sensitive detection of brain-derived neurotrophic factor (BDNF) in the brain of freely moving mice using an interdigitated microelectrode (IME) biosensor.
abstract: Brain-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 BDNF in 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.
authors.affiliation: Center for BioMicrosystems, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea.|Department of Electrical Engineering, Kwangwoon University, 447-1 Wolgye, Nowon, Seoul 01897, Korea.
authors.forename: Yong Kyoung
authors.initials: YK
authors.lastname: Yoo
authors.affiliation: Center for Neuroscience and Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea.
authors.forename: Jaekwang
authors.initials: J
authors.lastname: Lee
authors.affiliation: Center for BioMicrosystems, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea.
authors.forename: Jinsik
authors.initials: J
authors.lastname: Kim
authors.affiliation: Center for BioMicrosystems, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea.
authors.forename: Gangeun
authors.initials: G
authors.lastname: Kim
authors.affiliation: Center for Neuroscience and Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea.
authors.forename: Sunpil
authors.initials: S
authors.lastname: Kim
authors.affiliation: Center for Neuroscience and Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea.
authors.forename: Jeongyeon
authors.initials: J
authors.lastname: Kim
authors.affiliation: Center for Neuroscience and Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea.
authors.forename: Heejung
authors.initials: H
authors.lastname: Chun
authors.affiliation: Department of Electrical Engineering, Kwangwoon University, 447-1 Wolgye, Nowon, Seoul 01897, Korea.
authors.forename: Jeong Hoon
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Center for Neuroscience and Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea.
authors.forename: C Justin
authors.initials: CJ
authors.lastname: Lee
authors.affiliation: Center for BioMicrosystems, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea.
authors.forename: Kyo Seon
authors.initials: KS
authors.lastname: Hwang
mesh_terms: D000818:Animals; D015374:Biosensing Techniques / Q000379:methods*; D001921:Brain / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000134:cerebrospinal fluid / Q000378:metabolism*; D003956:Dialysis; D017097:Electric Impedance; D020868:Gene Silencing; D016086:Lentivirus / Q000378:metabolism; D051379:Mice; D008839:Microelectrodes; D009068:Movement; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D034741:RNA, Small Interfering