TY - JOUR
T1 - TGF-beta superfamily member activin A acts with BDNF and erythropoietin to improve survival of spiral ganglion neurons in vitro
AU - Kaiser, Odett
AU - Paasche, Gerrit
AU - Stöver, Timo
AU - Ernst, Stefanie
AU - Lenarz, Thomas
AU - Kral, Andrej
AU - Warnecke, Athanasia
PY - 2013/1/1
Y1 - 2013/1/1
N2 - 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.
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.
KW - Activin
KW - Brain-derived neurotrophic factor
KW - Erythropoietin
KW - Inner ear
KW - Spiral ganglion neurons
UR - http://www.scopus.com/inward/record.url?scp=84884297315&partnerID=8YFLogxK
U2 - 10.1016/j.neuropharm.2013.08.008
DO - 10.1016/j.neuropharm.2013.08.008
M3 - Article
C2 - 23973291
AN - SCOPUS:84884297315
SN - 0028-3908
VL - 75
SP - 416
EP - 425
JO - Neuropharmacology
JF - Neuropharmacology
ER -