单位:[1]Department of Otolaryngology-Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China临床科室耳鼻咽喉头颈外科耳鼻咽喉头颈外科首都医科大学附属北京友谊医院
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.
基金:
National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81900929, 81771016, 81830030, 81570912]; Beijing Natural Science FoundationBeijing Natural Science Foundation [7194256, 7212022]; Beijing Hospital Authority Youth Program [QML20180101]; Beijing Talents Fund [2018000021469G206]
第一作者单位:[1]Department of Otolaryngology-Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
通讯作者:
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.
推荐引用方式(GB/T 7714):
Guo Jing-Ying,He Lu,Chen Zhong-Rui,et al.AAV8-mediated Atoh1 overexpression induces dose-dependent regeneration of vestibular hair cells in adult mice[J].NEUROSCIENCE LETTERS.2021,747:doi:10.1016/j.neulet.2021.135679.
APA:
Guo Jing-Ying,He Lu,Chen Zhong-Rui,Liu Ke,Gong Shu-Sheng&Wang Guo-Peng.(2021).AAV8-mediated Atoh1 overexpression induces dose-dependent regeneration of vestibular hair cells in adult mice.NEUROSCIENCE LETTERS,747,
MLA:
Guo Jing-Ying,et al."AAV8-mediated Atoh1 overexpression induces dose-dependent regeneration of vestibular hair cells in adult mice".NEUROSCIENCE LETTERS 747.(2021)