Effects of Localized Neurotrophin Gene Expression on Spiral Ganglion Neuron Resprouting in the Deafened Cochlea
Effects of Localized Neurotrophin Gene Expression on Spiral Ganglion Neuron Resprouting in the Deafened Cochlea
复制标题
DOI：
10.1038/mt.2010.28
复制
发表时间：
2010-06-01
影响因子：
12.4
通讯作者：
Richardson, Rachael T.
中科院分区：
文献类型：
--
作者：
Wise, Andrew K.;Hume, Clifford R.;Richardson, Rachael T.
重度感音神经性听力损失（SNHL）患者可使用人工耳蜗电刺激螺旋神经节神经元（sgn）。然而，这些神经元在SNHL后由于失去通常由感觉毛细胞（HCs）提供的神经营养物质而逐渐退化。实验表明，外源性神经营养因子可防止SGN变性，但也可导致其周围纤维的异常再生。本研究旨在创造一种目标来源的神经营养因子，以增加SNHL后神经元的存活和重定向纤维再生。将表达绿色荧光蛋白（GFP）的腺病毒（Ad）载体单独或联合脑源性神经营养因子（BDNF）或神经营养因子-3 （NT3）注射到氨基糖苷致聋的豚鼠耳蜗或耳膜介质中，持续1周。3周后，检测耳蜗基因表达、神经元存活和外周纤维对基因表达的反应。将载体注射到scala培养基中，基因表达比注射到scala鼓室中更局部，并且在Corti部分变性器官中观察到的基因表达一致。神经细胞存活率更高，并且有证据表明，中scala注射后，Corti器官内的局部纤维对神经营养因子表达细胞有反应（P < 0.05），这是通过基因治疗促进听觉外周纤维有组织再生的第一步。
A cochlear implant may be used to electrically stimulate spiral ganglion neurons (SGNs) in people with severe sensorineural hearing loss (SNHL). However, these neurons progressively degenerate after SNHL due to loss of neurotrophins normally supplied by sensory hair cells (HCs). Experimentally, exogenous neurotrophin administration prevents SGN degeneration but can also result in abnormal resprouting of their peripheral fibers. This study aimed to create a target-derived neurotrophin source to increase neuron survival and redirect fiber resprouting following SNHL. Adenoviral (Ad) vectors expressing green fluorescent protein (GFP) alone or in combination with brain-derived neurotrophic factor (BDNF) or neurotrophin-3 (NT3) were injected into the cochlear scala tympani or scala media of guinea-pigs (GPs) deafened via aminoglycosides for 1 week. After 3 weeks, cochleae were examined for gene expression, neuron survival, and the projection of peripheral fibers in response to gene expression. Injection of vectors into the scala media resulted in more localized gene expression than scala tympani injection with gene expression consistently observed within the partially degenerated organ of Corti. There was also greater neuron survival and evidence of localized fiber responses to neurotrophin-expressing cells within the organ of Corti from scala media injections (P < 0.05), a first step in promoting organized resprouting of auditory peripheral fibers via gene therapy.