Administration of transforming growth factor-α enhances anatomical and behavioral recovery following olfactory nerve transection

C. D. Herzog, T. Otto

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Although replacement of olfactory receptor neurons (ORNs) and subsequent reinnervation of the olfactory bulb occur following ORN injury, the intrinsic and extrinsic factors that contribute to the regulation of this dynamic process have not yet been fully identified. Recent research indicates that several growth factors have neurogenic effects on ORNs in vitro, and that chronic in vivo administration of either basic fibroblast growth factor, epidermal growth factor, or transforming growth factor-α (TGF-α) following chemical lesion can enhance the normal rate of ORN reinnervation of the olfactory bulb. The primary goal of the present experiments was to further assess the extent to which growth factor-related enhancements in the rate of anatomical recovery during ORN reconstitution and subsequent reinnervation of olfactory bulb are accompanied by enhancements in the rate of recovery of odor-guided behavior. A series of experiments in rats was conducted to initially characterize the time course of the anatomical and behavioral recovery normally observed following ORN reconstitution as a consequence of olfactory nerve transection, and to subsequently characterize the anatomical and behavioral effects of TGF-α administration on this normal rate of recovery. Consistent with a host of prior studies, olfactory nerve transection produced consistent and substantial deafferentation of olfactory bulb followed by a time-dependent anatomical recovery which was significantly enhanced by administration of TGF-α. The effect of TGF-α on functional recovery following olfactory nerve transection was also assessed using an odor-guided fear conditioning task. ORN lesioned animals receiving injections of TGF-α during recovery were found to display enhanced conditioned responding to an olfactory stimulus compared to untreated subjects. Further behavioral analyses suggested that this enhanced functional recovery was likely not due to non-specific effects of TGF-α on cognition or motor activity, but rather to enhanced olfactory input to the CNS. Future studies will likely reveal the exact mechanism of action mediating the anatomical and concomitant behavioral effects of this growth factor. Since ORNs are one of only a few populations of neurons capable of regeneration or replacement, the continued study of the cellular and molecular factors that coordinate this regenerative process may ultimately lead to the development of therapeutic strategies to promote an enhanced functional recovery following injury to other neuronal populations.

Original languageEnglish (US)
Pages (from-to)569-580
Number of pages12
JournalNeuroscience
Volume113
Issue number3
DOIs
StatePublished - Sep 2 2002

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Keywords

  • Fear conditioning
  • Growth factors
  • Neurogenesis
  • Olfactory bulb
  • Olfactory receptor neuron
  • Rat
  • Transforming growth factor-α

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