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

Injury to peripheral nerves often results in structural and functional chan ges in the dorsal root ganglia (DRG). Although the mechanisms underlying th ese changes remain largely unknown, satellite cell activation and up-regula tion of several neurotrophic factors in the DRG occur in response to the ne rve lesion, modulating the plasticity of affected neurons. To investigate p otential roles of transforming growth factor a (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), molec ules 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 rec eptor are expressed mainly in small neurons and satellite cells surrounding some large or medium-sized neurons as determined by immunohistochemistry a nd in situ hybridization. In response to sciatic nerve lesion, there was a marked and differential up-regulation of TGF-alpha and EGF receptor express ion within DRG, evident as early as 24 h after lesion and lasting for at le ast 14 days. While the up-regulated TGF-alpha was localized mainly on satel lite cells in the ipsilateral and contralateral DRGs, EGF receptor up-regul ation was mainly neuronal (with the expression expanding to include all neu rons) in the ipsilateral DRGs, but mainly glial in the contralateral DRGs. These changes in TGF-alpha and its receptor expression suggest that TGF-alp ha may play a role in the satellite cell proliferation and/or activation as well as in neuronal survival after nerve lesion. (C) 1999 Academic Press.