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 beta-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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenoviridae / genetics
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Age Factors
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Animals
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Animals, Newborn
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Axotomy
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Cell Death / drug effects
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Chickens
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Facial Nerve Injuries / genetics
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Facial Nerve Injuries / physiopathology*
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Facial Nerve Injuries / therapy
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Gene Expression Profiling
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Gene Expression Regulation
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Genetic Therapy
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Genetic Vectors / therapeutic use
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Hedgehog Proteins
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Motor Neurons / metabolism
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Motor Neurons / pathology
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Nerve Regeneration / genetics
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Nerve Regeneration / physiology*
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Nerve Tissue Proteins / biosynthesis
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / physiology*
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RNA, Messenger / biosynthesis
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RNA, Messenger / genetics
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Rats
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Rats, Wistar
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Receptors, G-Protein-Coupled / biosynthesis
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Receptors, G-Protein-Coupled / genetics
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Receptors, G-Protein-Coupled / physiology*
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Recombinant Fusion Proteins / physiology
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Smoothened Receptor
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Trans-Activators / biosynthesis
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Trans-Activators / genetics
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Trans-Activators / physiology*
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Up-Regulation
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Veratrum Alkaloids / toxicity
Substances
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Hedgehog Proteins
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Nerve Tissue Proteins
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RNA, Messenger
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Receptors, G-Protein-Coupled
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Recombinant Fusion Proteins
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Smo protein, rat
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Smoothened Receptor
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Trans-Activators
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Veratrum Alkaloids
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cyclopamine