Agterberg Martijn J H, Versnel Huib, de Groot John C M J, Smoorenburg Guido F, Albers Frans W J, Klis Sjaak F L
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.
Hear Res. 2008 Oct;244(1-2):25-34. doi: 10.1016/j.heares.2008.07.004. Epub 2008 Jul 25.
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.
当豚鼠因耳毒性药物致聋时,螺旋神经节细胞(SGCs)会逐渐退化。应用神经营养因子可阻止这一过程。然而,获救的SGCs的形态变化尚未进行定量测定。有可能用神经生长因子处理过的SGCs比听力正常的豚鼠耳蜗中的SGCs更脆弱。因此,研究了I型SGCs的线粒体和髓鞘形成,并测定了胞体面积、细胞圆度和电子密度。通过皮下注射卡那霉素,随后静脉输注速尿使豚鼠致聋。在致聋程序两周后开始给予脑源性神经营养因子(BDNF),并持续四周。研究了四组耳蜗:(1)听力正常的豚鼠的耳蜗;(2)致聋两周后的豚鼠的耳蜗;(3)致聋六周后的豚鼠的耳蜗;(4)致聋后用BDNF处理的耳蜗。致聋程序导致SGCs逐渐丧失。致聋六周后,未处理的剩余SGCs的线粒体大小、胞体面积和细胞圆度减小,髓鞘层数减少。在耳蜗基部,BDNF治疗使SGCs免于退化。用BDNF处理的SGCs比听力正常的豚鼠的SGCs更大,而圆度值正常,电子密度不变。与听力正常的豚鼠的SGCs的髓鞘层数相比,用BDNF处理的SGCs的髓鞘层数减少。SGCs的形态变化可能与据报道在停止BDNF治疗后发生的SGCs的快速丧失有关。