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Therapeutic value of nerve growth factor in promoting neural stem cell survival and differentiation and protecting against neuronal hearing loss

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Abstract

Nerve growth factor (NGF) is a neurotrophic factor that modulates survival and differentiation of neural stem cells (NSCs). We investigated the function of NGF in promoting growth and neuronal differentiation of NSCs isolated from mouse cochlear tissue, as well as its protective properties against gentamicin (GMC) ototoxicity. NSCs were isolated from the cochlea of mice and cultured in vitro. Effect of NGF on survival, neurosphere formation, and differentiation of the NSCs, as well as neurite outgrowth and neural excitability in the subsequent in vitro neuronal network, was examined. Mechanotransduction capacity of intact cochlea and auditory brainstem response (ABR) threshold in mice were also measured following GMC treatment to evaluate protection using NGF against GMC-induced neuronal hearing loss. NGF improved survival, neurosphere formation, and neuronal differentiation of mouse cochlear NSCs in vitro, as well as promoted neurite outgrowth and neural excitability in the NSC-differentiated neuronal culture. In addition, NGF protected mechanotransduction capacity and restored ABR threshold in gentamicin ototoxicity mouse model. Our study supports a potential therapeutic value of NGF in promoting proliferation and differentiation of NSCs into functional neurons in vitro, supporting its protective role in the treatment of neuronal hearing loss.

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Funding

This work was supported by grant from the National Natural Science Foundation of China (NSFC, 81371093) to Zhao Han.

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    Authors and Affiliations

    1. Department of Otology and Skull Base Surgery, Eye Ear Nose and Throat Hospital, Fudan University, Shanghai, 200031, China

      Zhao Han, Ning Cong, Yu-Yan Gu, Rui Ma & Fang-Lu Chi

    2. Shanghai Auditory Medical Center, Shanghai, China

      Zhao Han, Ning Cong, Yu-Yan Gu, Rui Ma & Fang-Lu Chi

    3. Key Laboratory of Hearing Science, Ministry of Health, Shanghai, China

      Zhao Han, Ning Cong, Yu-Yan Gu, Rui Ma & Fang-Lu Chi

    4. Fudan University, Shanghai, China

      Zhao Han, Ning Cong, Yu-Yan Gu, Rui Ma & Fang-Lu Chi

    5. Department of Pharmacy, Eye Ear Nose & Throat Hospital, Fudan University, 83 Fenyang Road, Shanghai, 200031, China

      Cong-Pin Wang

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    1. Zhao Han
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    Correspondence to Zhao Han or Fang-Lu Chi.

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    Zhao Han and Cong-Pin Wang have contributed equally to this paper.

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    Han, Z., Wang, CP., Cong, N. et al. Therapeutic value of nerve growth factor in promoting neural stem cell survival and differentiation and protecting against neuronal hearing loss. Mol Cell Biochem 428, 149–159 (2017). https://doi.org/10.1007/s11010-016-2925-5

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