Neurite outgrowth on cultured spiral ganglion neurons induced by erythropoietin.
The morphological correlate of deafness is the loss of hair cells with subsequent degeneration of spiral ganglion neurons (SGN). Neurotrophic factors have a neuroprotective effect, and especially brain-derived neurotrophic factor (BDNF) has been demonstrated to protect SGN in vitro and after ototoxic trauma in vivo. Erythropoietin (EPO) attenuates hair cell loss in rat cochlea explants that were treated with gentamycin. Recently, it has also been shown that EPO reduces the apoptose rate in hippocampal neurons. Therefore, the aim of the study was to examine the effects of EPO on SGN in vitro. Spiral ganglion cells were isolated from neonatal rats and cultured for 48 h in serum-free medium supplemented with EPO and/or BDNF. Results showed that survival rates of SGN were not significantly improved when cultivated with EPO alone. Also, EPO did not further increase BDNF-induced survival of SGN. However, significant elongation of neurites was determined when SGN were cultivated with EPO alone. Even though a less than additive effect was observed, combined treatment with BDNF and EPO led to a significant elongation of neurites when compared to individual treatment with BDNF or EPO. It can be concluded that EPO induces neurite outgrowth rather than promoting survival. Thus, EPO presents as an interesting candidate to enhance and modulate the regenerative effect of BDNF on SGN.
Berkingali
Nurdanat
N
Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Hannover, Hannover, Germany.
Warnecke
Athanasia
A
Gomes
Priya
P
Paasche
Gerrit
G
Tack
Jan
J
Lenarz
Thomas
T
Stöver
Timo
T
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004921:Erythropoietin / Q000494:pharmacology*; D007150:Immunohistochemistry; D009416:Nerve Regeneration / Q000187:drug effects; D016501:Neurites / Q000187:drug effects* / Q000648:ultrastructure*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D017467:Receptors, Erythropoietin / Q000378:metabolism; D011994:Recombinant Proteins; D013136:Spiral Ganglion / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure*
D019208:Brain-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; D017467:Receptors, Erythropoietin; D011994:Recombinant Proteins; D004921:Erythropoietin