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The Journal of Neuroscience, September 8, 2004, 24(36):7923-7930; doi:10.1523/JNEUROSCI.1784-04.2004

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Development/Plasticity/Repair
The Upregulated Expression of Sonic Hedgehog in Motor Neurons after Rat Facial Nerve Axotomy

Chihiro Akazawa,¹ Hayami Tsuzuki,¹ Yasuko Nakamura,¹ Yo Sasaki,¹ Kanae Ohsaki,² Shun Nakamura,² Yoshihiro Arakawa,³ and Shinichi Kohsaka¹

Departments of ¹Neurochemistry and ²Biochemistry and Cellular Biology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8502, Japan, and ³Department of Clinical Research Center, Branch Hospital, Faculty of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan

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-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.

Key words: Shh; neuronal death; axotomy; facial nerve; motor neuron; adenovirus

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Received Sep 9, 2003; revised July 12, 2004; accepted July 14, 2004.

This article has been cited by other articles:

				W.-K. Kim, V. Meliton, K. W. Park, C. Hong, P. Tontonoz, P. Niewiadomski, J. A. Waschek, S. Tetradis, and F. Parhami Negative Regulation of Hedgehog Signaling by Liver X Receptors Mol. Endocrinol., October 1, 2009; 23(10): 1532 - 1543. [Abstract] [Full Text] [PDF]

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