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AAV8-mediated Atoh1 overexpression induces dose-dependent regeneration of vestibular hair cells in adult mice

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单位: [1]Department of Otolaryngology-Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
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关键词: Adeno-associated virus Atoh1 Vestibule Hair cell Regeneration Stereocilium

摘要:
Vestibular hair cells (HCs) are mechanoreceptors for the detection of head movement. Vestibular HCs of adult mammals never completely regenerate after damage, resulting in vestibular dysfunction. Overexpression of Atoh1 is effective for inducing HC regeneration. However, method of clinical feasibility and improvement of regenerative extent are both in need. Here we used an adeno-associated virus (AAV) serotype 8 vector of two different titers to overexpress Atoh1 in the injured utricles of adult mice. One month after virus inoculation, abundant myosin VIIa-positive cells and immature stereocilia were observed. Quantitative analyses revealed that Atoh1 overexpression replenished vestibular HCs in a dose-dependent manner. Vectors of a higher titer increased the number of myosin VIIa-positive cells compared to those of lower titer. Moreover, only Atoh1 overexpression in the higher titer group enhanced stereocilium regeneration, which is an important step in the maturation of regenerated HCs. Although the current treatment failed to initiate functional recovery of the animals, our results prompt further improvements in the recovery of vestibular dysfunction by AAV.

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出版当年[2020]版:
大类 | 4 区 医学
小类 | 4 区 神经科学
最新[2025]版:
大类 | 4 区 医学
小类 | 4 区 神经科学
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出版当年[2019]版:
Q3 NEUROSCIENCES
最新[2023]版:
Q3 NEUROSCIENCES

影响因子: 最新[2023版] 最新五年平均[2021-2025] 出版当年[2019版] 出版当年五年平均[2015-2019] 出版前一年[2018版] 出版后一年[2020版]

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第一作者单位: [1]Department of Otolaryngology-Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
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通讯机构: [1]Department of Otolaryngology-Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China [*1]Department of Otolaryngology Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University, 95th Yong’an Road, Xicheng District, Beijing, 100050, China.
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