PMID- 23973291
OWN - NLM
STAT- MEDLINE
DCOM- 20140819
LR  - 20131216
IS  - 1873-7064 (Electronic)
IS  - 0028-3908 (Linking)
VI  - 75
DP  - 2013 Dec
TI  - TGF-beta superfamily member activin A acts with BDNF and erythropoietin to 
      improve survival of spiral ganglion neurons in vitro.
PG  - 416-25
LID - S0028-3908(13)00365-1 [pii]
LID - 10.1016/j.neuropharm.2013.08.008 [doi]
AB  - Activins are regulators of embryogenesis, osteogenesis, hormones and neuronal 
      survival. Even though activin receptor type II has been detected in spiral 
      ganglion neurons (SGN), little is known about the role of activins in the inner 
      ear. An activin-mediated neuroprotection is of considerable clinical interest 
      since SGN are targets of electrical stimulation with cochlear implants in hearing 
      impaired patients. Thus, the presence of activin type-I and type-II receptors was 
      demonstrated immunocytochemically and the individual and combined effects of 
      activin A, erythropoietin (EPO) and brain-derived neurotrophic factor (BDNF) on 
      SGN were examined in vitro. SGN isolated from neonatal rats (P 3-5) were cultured 
      in serum-free medium supplemented with activin A, BDNF and EPO. Compared to the 
      negative control, survival rates of SGN were significantly improved when 
      cultivated individually with activin A (p<0.001) and in combination with BDNF 
      (p<0.001). Neither neurite outgrowth nor neuronal survival was influenced by the 
      addition of EPO to activin A-treated neurons. However, when all three factors 
      were added, a significantly (p<0.001) improved neuronal survival was observed 
      (61.2+/-3.6%) compared to activin A (25.4+/-2.1%), BDNF (22.8+/-3.3%) and BDNF+EPO 
      (19.2+/-1.5%). Under the influence of the EPO-inhibitors, this increase in neuronal 
      survival was blocked. Acting with BDNF and EPO to promote neuronal survival in 
      vitro, activin A presents an interesting factor for pharmacological intervention 
      in the inner ear. The present study demonstrates a synergetic effect of a 
      combined therapy with several trophic factors.
CI  - Copyright (c) 2013 Elsevier Ltd. All rights reserved.
FAU - Kaiser, Odett
AU  - Kaiser O
AD  - Department of Otolaryngology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 
      Hannover, Germany. Electronic address: odettgenerlich@gmx.de.
FAU - Paasche, Gerrit
AU  - Paasche G
AD  - Department of Otolaryngology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 
      Hannover, Germany.
FAU - Stover, Timo
AU  - Stover T
AD  - Department of Otolaryngology, University Hospital, Johann Wolfgang Goethe 
      University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
FAU - Ernst, Stefanie
AU  - Ernst S
AD  - Institute for Biometry, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 
      Hannover, Germany.
FAU - Lenarz, Thomas
AU  - Lenarz T
AD  - Department of Otolaryngology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 
      Hannover, Germany.
FAU - Kral, Andrej
AU  - Kral A
AD  - Department of Otolaryngology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 
      Hannover, Germany.
FAU - Warnecke, Athanasia
AU  - Warnecke A
AD  - Department of Otolaryngology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 
      Hannover, Germany. Electronic address: warnecke.athanasia@mh-hannover.de.
LA  - eng
PT  - Journal Article
DEP - 20130822
PL  - England
TA  - Neuropharmacology
JT  - Neuropharmacology
JID - 0236217
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Culture Media, Serum-Free)
RN  - 0 (Drug Combinations)
RN  - 0 (Follistatin)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (activin A)
RN  - 104625-48-1 (Activins)
RN  - 11096-26-7 (Erythropoietin)
SB  - IM
MH  - Activins/*pharmacology
MH  - Animals
MH  - Animals, Newborn
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Culture Media, Serum-Free/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Drug Combinations
MH  - Erythropoietin/*pharmacology
MH  - Female
MH  - Follistatin/metabolism
MH  - Male
MH  - Nerve Tissue Proteins/metabolism
MH  - Neurons/*drug effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Spiral Ganglion/*cytology
OTO - NOTNLM
OT  - Activin
OT  - Brain-derived neurotrophic factor
OT  - Erythropoietin
OT  - Inner ear
OT  - Spiral ganglion neurons
EDAT- 2013/08/27 06:00
MHDA- 2014/08/20 06:00
CRDT- 2013/08/27 06:00
PHST- 2013/04/25 00:00 [received]
PHST- 2013/07/03 00:00 [revised]
PHST- 2013/08/08 00:00 [accepted]
PHST- 2013/08/27 06:00 [entrez]
PHST- 2013/08/27 06:00 [pubmed]
PHST- 2014/08/20 06:00 [medline]
AID - S0028-3908(13)00365-1 [pii]
AID - 10.1016/j.neuropharm.2013.08.008 [doi]
PST - ppublish
SO  - Neuropharmacology. 2013 Dec;75:416-25. doi: 10.1016/j.neuropharm.2013.08.008. 
      Epub 2013 Aug 22.