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The spread of adenoviral vectors to central nervous system through pathway of cochlea in mimetic aging and young rats

Gene Therapy volume 22, pages 866–875 (2015)Cite this article

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Abstract

There is no definitive conclusion concerning the spread of viral vectors to the brain after a cochlear inoculation. In addition, some studies have reported different distribution profiles of viral vectors in the central auditory system after a cochlear inoculation. Thus, rats were grouped into either a mimetic aging group or a young group and transfected with adenoviral vectors (AdVs) by round window membrane injection. The distribution of AdV in central nervous system (CNS) was demonstrated in the two groups with transmission electron microscopy and immunofluorescence. We found that the AdV could disseminate into the CNS and that the neuronal damage and stress-induced GRP78 expression were reduced after transfection with PGC-1α, as compared with the control vectors, especially in the mimetic aging group. We also found that the host immune response was degraded in CNS in the mimetic aging group after transduction through the cochlea, as compared with the young group. These results demonstrate that viral vectors can disseminate into the CNS through the cochlea. Moreover, mimetic aging induced by D-galactose could facilitate the spread of viral vectors into the CNS from the cochlea. These findings may indicate a new potential approach for gene therapy against age-related diseases in the CNS.

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Acknowledgements

This work was supported by grants from the Major State Basic Research Development Program of China (973 Program; No. 2011CB504504), National Nature Science Foundation of China (No. 81230021 and No. 81000409) and International S&T Cooperation Program of China (No. 2013DFE33160). We thank Baoping Chen and Senlin Lei for the help of transmission electronic microscopy.

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  1. X Chen, X Zhao and Y Hu: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Otolaryngology–Head and Neck Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    X Chen, X Zhao, Y Hu, F Lan, H Sun, G Fan, Y Sun, J Wu & W Kong

  2. Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    W Kong

  3. Research Institute of Otorhinolaryngology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    W Kong

  4. Key Laboratory of Neurological Disease, Ministry of Education, Wuhan, China

    W Kong

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Chen, X., Zhao, X., Hu, Y. et al. The spread of adenoviral vectors to central nervous system through pathway of cochlea in mimetic aging and young rats. Gene Ther 22, 866–875 (2015). https://doi.org/10.1038/gt.2015.63

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