PMID- 30971872
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 1662-4548 (Print)
IS  - 1662-453X (Electronic)
IS  - 1662-453X (Linking)
VI  - 13
DP  - 2019
TI  - Detection of BDNF-Related Proteins in Human Perilymph in Patients With Hearing 
      Loss.
PG  - 214
LID - 10.3389/fnins.2019.00214 [doi]
LID - 214
AB  - The outcome of cochlear implantation depends on multiple variables including the 
      underlying health of the cochlea. Brain derived neurotrophic factor (BDNF) has 
      been shown to support spiral ganglion neurons and to improve implant function in 
      animal models. Whether endogenous BDNF or BDNF-regulated proteins can be used as 
      biomarkers to predict cochlear health and implant outcome has not been 
      investigated yet. Gene expression of BDNF and downstream signaling molecules were 
      identified in tissue of human cochleae obtained from normal hearing patients (n = 
      3) during skull base surgeries. Based on the gene expression data, bioinformatic 
      analysis was utilized to predict the regulation of proteins by BDNF. The presence 
      of proteins corresponding to these genes was investigated in perilymph (n = 41) 
      obtained from hearing-impaired patients (n = 38) during cochlear implantation or 
      skull base surgery for removal of vestibular schwannoma by nanoscale liquid 
      chromatography coupled to tandem mass spectrometry (nano LC-MS/MS). Analyzed by 
      mass spectrometry were 41 perilymph samples despite three patients undergoing 
      bilateral cochlear implantation. These particular BDNF regulated proteins were 
      not detectable in any of the perilymph samples. Subsequently, targeted analysis 
      of the perilymph proteome data with Ingenuity Pathway Analysis (IPA) identified 
      further proteins in human perilymph that could be regulated by BDNF. These BDNF 
      regulated proteins were correlated to the presence of residual hearing (RH) prior 
      to implantation and to the performance data with the cochlear implant after 1 
      year. There was overall a decreased level of expression of BDNF-regulated 
      proteins in profoundly hearing-impaired patients compared to patients with some 
      RH. Phospholipid transfer protein was positively correlated to the preoperative 
      hearing level of the patients. Our data show that combination of gene expression 
      arrays and bioinformatic analysis can aid in the prediction of downstream 
      signaling proteins related to the BDNF pathway. Proteomic analysis of perilymph 
      may help to identify the presence or absence of these molecules in the diseased 
      organ. The impact of such prediction algorithms on diagnosis and treatment needs 
      to be established in further studies.
FAU - de Vries, Ines
AU  - de Vries I
AD  - Department of Otolaryngology, Hannover Medical School, Hanover, Germany.
FAU - Schmitt, Heike
AU  - Schmitt H
AD  - Department of Otolaryngology, Hannover Medical School, Hanover, Germany.
AD  - Cluster of Excellence Hearing4all, German Research Foundation, Hannover Medical 
      School, Hanover, Germany.
FAU - Lenarz, Thomas
AU  - Lenarz T
AD  - Department of Otolaryngology, Hannover Medical School, Hanover, Germany.
AD  - Cluster of Excellence Hearing4all, German Research Foundation, Hannover Medical 
      School, Hanover, Germany.
FAU - Prenzler, Nils
AU  - Prenzler N
AD  - Department of Otolaryngology, Hannover Medical School, Hanover, Germany.
FAU - Alvi, Sameer
AU  - Alvi S
AD  - Department of Otolaryngology, Head and Neck Surgery, University of Kansas School 
      of Medicine, Kansas City, MO, United States.
FAU - Staecker, Hinrich
AU  - Staecker H
AD  - Department of Otolaryngology, Head and Neck Surgery, University of Kansas School 
      of Medicine, Kansas City, MO, United States.
FAU - Durisin, Martin
AU  - Durisin M
AD  - Department of Otolaryngology, Hannover Medical School, Hanover, Germany.
FAU - Warnecke, Athanasia
AU  - Warnecke A
AD  - Department of Otolaryngology, Hannover Medical School, Hanover, Germany.
AD  - Cluster of Excellence Hearing4all, German Research Foundation, Hannover Medical 
      School, Hanover, Germany.
LA  - eng
PT  - Journal Article
DEP - 20190326
PL  - Switzerland
TA  - Front Neurosci
JT  - Frontiers in neuroscience
JID - 101478481
PMC - PMC6445295
OTO - NOTNLM
OT  - BDNF
OT  - bioinformatic analysis
OT  - cochlear implant
OT  - diagnostics
OT  - inner ear
OT  - neurotrophin
OT  - perilymph
OT  - proteomics
EDAT- 2019/04/12 06:00
MHDA- 2019/04/12 06:01
PMCR- 2019/01/01
CRDT- 2019/04/12 06:00
PHST- 2018/10/18 00:00 [received]
PHST- 2019/02/25 00:00 [accepted]
PHST- 2019/04/12 06:00 [entrez]
PHST- 2019/04/12 06:00 [pubmed]
PHST- 2019/04/12 06:01 [medline]
PHST- 2019/01/01 00:00 [pmc-release]
AID - 10.3389/fnins.2019.00214 [doi]
PST - epublish
SO  - Front Neurosci. 2019 Mar 26;13:214. doi: 10.3389/fnins.2019.00214. eCollection 
      2019.