局部神经营养因子基因表达对耳聋耳蜗螺旋神经节神经元再生的影响。
Effects of localized neurotrophin gene expression on spiral ganglion neuron resprouting in the deafened cochlea.
机构信息
Bionic Ear Institute, East Melbourne, Victoria, Australia.
出版信息
Mol Ther. 2010 Jun;18(6):1111-22. doi: 10.1038/mt.2010.28. Epub 2010 Mar 9.
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.
人工耳蜗可用于对患有严重感觉神经性听力损失(SNHL)的人进行电刺激螺旋神经节神经元(SGN)。然而,由于感觉毛细胞(HCs)正常供应的神经营养因子丧失,这些神经元在 SNHL 后会逐渐退化。在实验中,外源性神经营养因子的给予可防止 SGN 退化,但也可能导致其外周纤维异常再生。本研究旨在创建一种靶源性神经营养源,以增加神经元的存活并在 SNHL 后重新引导纤维再生。将单独表达绿色荧光蛋白(GFP)或与脑源性神经营养因子(BDNF)或神经营养因子-3(NT3)组合的腺病毒(Ad)载体注入氨基糖苷类药物致聋的豚鼠(GP)耳蜗鼓阶或中阶。3 周后,检查耳蜗的基因表达、神经元存活以及外周纤维对基因表达的投射情况。与鼓阶注射相比,中阶注射的载体导致更局部的基因表达,基因表达始终在部分退化的 Corti 器官内观察到。从中阶注射的 Corti 器官内的神经营养因子表达细胞中也观察到了更多的神经元存活和局部纤维反应的证据(P < 0.05),这是通过基因治疗促进有组织的听觉外周纤维再生的第一步。