The upregulated expression of Sonic hedgehog in motor neurons after rat facial nerve axotomy

Chihiro Akazawa, Hayami Tsuzuki, Yasuko Nakamura, Yo Sasaki, Kanae Ohsaki, Shun Nakamura, Yoshihiro Arakawa, Shinichi Kohsaka

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

Abstract

Nerve injury leads to the induction of a large number of genes to repair the damage and to restore synaptic transmission. We have attempted to identify molecules whose mRNA expression is altered in response to facial nerve axotomy. Here we report that facial nerve axotomy upregulates Sonic hedgehog (Shh) and its receptor Smoothened (Smo) in facial motor neurons of adult rats, whereas facial nerve axotomy does not upregulate mRNA of Shh or Smo in neonatal rats. We tested whether overexpression of Shh in facial motor neurons of axotomized neonatal rats may promote neuronal survival. Adenovirus-mediated overexpression of Shh, but not that of β-galactosidase, transiently rescues axotomy-induced neuronal cell death for 3-5 d after axotomy. Finally, the pharmacological inhibitor of Shh signaling, cyclopamine, induces motor neuron death in adult rats after axotomy. These results suggest that Shh plays a regulatory role in nerve injury.

Original languageEnglish
Pages (from-to)7923-7930
Number of pages8
JournalJournal of Neuroscience
Volume24
Issue number36
DOIs
StatePublished - Sep 8 2004

Keywords

  • Adenovirus
  • Axotomy
  • Facial nerve
  • Motor neuron
  • Neuronal death
  • Shh

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