Morphological changes in spiral ganglion cells after intracochlear application of brain-derived neurotrophic factor in deafened guinea pigs.
When guinea pigs are deafened with ototoxic drugs spiral ganglion cells (SGCs) degenerate progressively. Application of neurotrophins can prevent this process. Morphological changes of rescued SGCs have not been quantitatively determined yet. It might be that SGCs treated with neurotrophins are more vulnerable than SGCs in cochleae of normal-hearing guinea pigs. Therefore, the mitochondria and myelinisation of type-I SGCs were studied and the perikaryal area, cell circularity and electron density were determined. Guinea pigs were deafened with a subcutaneous injection of kanamycin followed by intravenous infusion of furosemide. Brain-derived neurotrophic factor (BDNF) delivery was started two weeks after the deafening procedure and continued for four weeks. Four cohorts of cochleae were studied: (1) cochleae of normal-hearing guinea pigs; (2) of guinea pigs two weeks after deafening; (3) six weeks after deafening; (4) cochleae treated with BDNF after deafening. The deafening procedure resulted in a progressive loss of SGCs. Six weeks after deafening the size of mitochondria, perikaryal area and cell circularity of the remaining untreated SGCs were decreased and the number of layers of the myelin sheath was reduced. In the basal part of the cochlea BDNF treatment rescued SGCs from degeneration. SGCs treated with BDNF were larger than SGCs in normal-hearing guinea pigs, whereas circularity had normal values and electron density was unchanged. The number of layers in the myelin sheath of BDNF-treated SGCs was reduced as compared to the number of layers in the myelin sheath of SGCs in normal-hearing guinea pigs. The morphological changes of SGCs might be related to the rapid loss of SGCs that has been reported to occur after cessation of BDNF treatment.
Agterberg
Martijn J H
MJ
Department of Otorhinolaryngology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Room G.02.531, P.O. Box 85500, 3508 GA Utrecht, The Netherlands. m.j.h.agterberg@umcutrecht.nl
Versnel
Huib
H
de Groot
John C M J
JC
Smoorenburg
Guido F
GF
Albers
Frans W J
FW
Klis
Sjaak F L
SF
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D003051:Cochlea / Q000378:metabolism; D004583:Electrons; D005260:Female; D005665:Furosemide / Q000494:pharmacology; D006168:Guinea Pigs; D007612:Kanamycin / Q000494:pharmacology; D008854:Microscopy, Electron; D008928:Mitochondria / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D013136:Spiral Ganglion / Q000473:pathology*
D019208:Brain-Derived Neurotrophic Factor; D007612:Kanamycin; D005665:Furosemide