PMID- 28596120
OWN - NLM
STAT- MEDLINE
DCOM- 20180522
LR  - 20231213
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Linking)
VI  - 357
DP  - 2017 Aug 15
TI  - Myelin-induced inhibition in a spiral ganglion organ culture - Approaching a 
      natural environment in vitro.
PG  - 75-83
LID - S0306-4522(17)30387-1 [pii]
LID - 10.1016/j.neuroscience.2017.05.053 [doi]
AB  - The performance of a cochlear implant depends on the defined interaction between 
      afferent neurons of the spiral ganglion and the inserted electrode. Neurite 
      outgrowth can be induced by neurotrophins such as brain-derived neurotrophic 
      factor (BDNF) via tropomyosin kinase receptor B (TrkB). However, neurotrophin 
      signaling through the p75 neurotrophin receptor (p75) inhibits neurite outgrowth 
      in the presence of myelin. Organotypic cultures derived from postnatal (P3-5) 
      mice were used to study myelin-induced inhibition in the cochlear spiral 
      ganglion. Neurite outgrowth was analyzed and quantified utilizing an adapted 
      Sholl analysis. Stimulation of neurite outgrowth was quantified after application 
      of BDNF, the selective TrkB agonist 7,8-dihydroxyflavone (7,8-DHF) and a 
      selective inhibitor of the Rho-associated kinase (Y27632), which inhibits the p75 
      pathway. Myelin-induced inhibition was assessed by application of 
      myelin-associated glycoprotein (MAG-Fc) to stimulate the inhibitory p75 pathway. 
      Inhibition of neurite outgrowth was achieved by the selective TrkB inhibitor 
      K252a. Stimulation of neurite outgrowth was observed after treatment with BDNF, 
      7,8 DHF and a combination of BDNF and Y27632. The 7,8-DHF-induced growth effects 
      could be inhibited by K252a. Furthermore, inhibition of neurite outgrowth was 
      observed after supplementation with MAG-Fc. Myelin-induced inhibition could be 
      overcome by 7,8-DHF and the combination of BDNF and Y27632. In this study, 
      myelin-induced inhibition of neurite outgrowth was established in a spiral 
      ganglion model. We reveal that 7,8-DHF is a viable novel compound for the 
      stimulation of neurite outgrowth in a myelin-induced inhibitory environment. The 
      combination of TrkB stimulation and ROCK inhibition can be used to overcome 
      myelin inhibition.
CI  - Copyright (c) 2017 IBRO. Published by Elsevier Ltd. All rights reserved.
FAU - Kramer, Benedikt
AU  - Kramer B
AD  - Department of Otorhinolaryngology - Head and Neck Surgery, Hearing Research 
      Centre Tubingen (THRC), University Tubingen, Germany.
FAU - Tropitzsch, Anke
AU  - Tropitzsch A
AD  - Department of Otorhinolaryngology - Head and Neck Surgery, Hearing Research 
      Centre Tubingen (THRC), University Tubingen, Germany.
FAU - Muller, Marcus
AU  - Muller M
AD  - Department of Otorhinolaryngology - Head and Neck Surgery, Hearing Research 
      Centre Tubingen (THRC), University Tubingen, Germany. Electronic address: 
      marcus.mueller@uni-tuebingen.de.
FAU - Lowenheim, Hubert
AU  - Lowenheim H
AD  - Department of Otorhinolaryngology - Head and Neck Surgery, Hearing Research 
      Centre Tubingen (THRC), University Tubingen, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170614
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (6,7-dihydroxyflavone)
RN  - 0 (Amides)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Carbazoles)
RN  - 0 (Flavones)
RN  - 0 (Indole Alkaloids)
RN  - 0 (Myelin Proteins)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Pyridines)
RN  - 0 (Receptors, Nerve Growth Factor)
RN  - 0 (Ngfr protein, mouse)
RN  - 138381-45-0 (Y 27632)
RN  - 97161-97-2 (staurosporine aglycone)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 2.7.11.1 (rho-Associated Kinases)
SB  - IM
MH  - Amides/pharmacology
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/administration & dosage/metabolism
MH  - Carbazoles/pharmacology
MH  - Flavones/pharmacology
MH  - Indole Alkaloids/pharmacology
MH  - Mice
MH  - Myelin Proteins/metabolism
MH  - Myelin Sheath/*metabolism
MH  - Nerve Growth Factors/pharmacology
MH  - Neuronal Outgrowth/drug effects/*physiology
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Pyridines/pharmacology
MH  - Receptor, trkB/agonists/antagonists & inhibitors/metabolism
MH  - Receptors, Nerve Growth Factor/metabolism
MH  - Spiral Ganglion/cytology/drug effects/*metabolism
MH  - *Tissue Culture Techniques
MH  - rho-Associated Kinases/antagonists & inhibitors/metabolism
OTO - NOTNLM
OT  - 7,8-DHF
OT  - BDNF
OT  - Y27632
OT  - cochlear implant
OT  - neurotrophin
OT  - spiral ganglion
EDAT- 2017/06/10 06:00
MHDA- 2018/05/23 06:00
CRDT- 2017/06/10 06:00
PHST- 2016/12/04 00:00 [received]
PHST- 2017/05/12 00:00 [revised]
PHST- 2017/05/30 00:00 [accepted]
PHST- 2017/06/10 06:00 [pubmed]
PHST- 2018/05/23 06:00 [medline]
PHST- 2017/06/10 06:00 [entrez]
AID - S0306-4522(17)30387-1 [pii]
AID - 10.1016/j.neuroscience.2017.05.053 [doi]
PST - ppublish
SO  - Neuroscience. 2017 Aug 15;357:75-83. doi: 10.1016/j.neuroscience.2017.05.053. 
      Epub 2017 Jun 14.