Rescue and Regrowth of Sensory Nerves Following Deafferentation by Neurotrophic Factors

Authors

  • R. A. ALTSCHULER,

    Corresponding author
    1. Kresge Hearing Research Institute, University of Michigan, 1301 East Ann Street, Ann Arbor, Michigan 48109–0506, USA
    2. Department of Anatomy and Cell Biology, University of Michigan, Ann Arbor, Michigan 48109–0506, USA
    Search for more papers by this author
  • Y. CHO,

    1. Kresge Hearing Research Institute, University of Michigan, 1301 East Ann Street, Ann Arbor, Michigan 48109–0506, USA
    2. Department of Anatomy and Cell Biology, University of Michigan, Ann Arbor, Michigan 48109–0506, USA
    Search for more papers by this author
  • J. YLIKOSKI,

    1. Institute of Biotechnology, University of Helsinki, P.O. Box 56, Viikinkaari 9, FIN-0014 Helsinki, Finland
    Search for more papers by this author
  • U. PIRVOLA,

    1. Institute of Biotechnology, University of Helsinki, P.O. Box 56, Viikinkaari 9, FIN-0014 Helsinki, Finland
    Search for more papers by this author
  • E. MAGAL,

    1. Department of Neurobiology, Amgen Inc., Thousand Oaks, California 91320, USA
    Search for more papers by this author
  • J. M. MILLER

    1. Kresge Hearing Research Institute, University of Michigan, 1301 East Ann Street, Ann Arbor, Michigan 48109–0506, USA
    Search for more papers by this author

eTo whom correspondence may be addressed. Phone: 734/763-0060; fax: 734/764-0014; e-mail: shuler@umich.edu

Abstract

ABSTRACT: Trauma and loss of cochlear inner hair cells causes a series of events that result first in the retraction of the peripheral processes of the auditory nerve, scar formation in the organ of Corti, and over the course of weeks to months (depending on the species) the loss of auditory nerve cell bodies (spiral ganglion cells). Neurotrophic factors play an important role in the mature nervous system as survival factors for maintenance and protection and also can play a role in regrowth. Studies in the cochlea now show that application of exogenous neurotrophic factors can enhance survival of spiral ganglion cells after deafness and induce regrowth of peripheral processes, perhaps by replacing lost endogenous factors. Combinations of factors may be most effective for achieving greatest survival and regrowth. Our studies find that brain-derived neurotrophic factor (BDNF) and glial-line-derived neurotrophic factor (GDNF) are very effective at enhancing spiral ganglion cell survival following deafness from ototoxic drugs or noise. It has also been found that BDNF plus fibroblast growth factor (FGF) is very effective at inducing process regrowth. Electrical stimulation also acts to enhance spiral ganglion cell survival, and the combination of electrical stimulation and neurotrophic factors could prove a most effective intervention.

Ancillary