Neuronal-glial differential expression of TGF-alpha and its receptor in the dorsal root ganglia in response to sciatic nerve lesion.

Abstract

Injury to peripheral nerves often results in structural and functional changes in the dorsal root ganglia (DRG). Although the mechanisms underlying these changes remain largely unknown, satellite cell activation and up-regulation of several neurotrophic factors in the DRG occur in response to the nerve lesion, modulating the plasticity of affected neurons. To investigate potential roles of transforming growth factor alpha (TGF-alpha) in these plastic changes in the DRG following a sciatic nerve transection, here we examined the expression in DRGs of TGF-alpha and its receptor (EGF receptor), molecules known to be mitogenic to glia and Schwann cells and to be neurotrophic for some differentiated neurons. In the normal DRGs, TGF-alpha and its receptor are expressed mainly in small neurons and satellite cells surrounding some large or medium-sized neurons as determined by immunohistochemistry and in situ hybridization. In response to sciatic nerve lesion, there was a marked and differential up-regulation of TGF-alpha and EGF receptor expression within DRG, evident as early as 24 h after lesion and lasting for at least 14 days. While the up-regulated TGF-alpha was localized mainly on satellite cells in the ipsilateral and contralateral DRGs, EGF receptor up-regulation was mainly neuronal (with the expression expanding to include all neurons) in the ipsilateral DRGs, but mainly glial in the contralateral DRGs. These changes in TGF-alpha and its receptor expression suggest that TGF-alpha may play a role in the satellite cell proliferation and/or activation as well as in neuronal survival after nerve lesion.