Effect of peripheral nerve lesion and lumbar sympathectomy on peptide regulation in dorsal root ganglia in the NGF-overexpressing mouse

Galanin is a peptide normally expressed at low levels both in sensory and i n sympathetic neurons, It is strongly upregulated after peripheral nerve le sions, and it has been proposed that nerve growth factor (NGF) plays a role in this regulation. In the present study the effect of both sciatic nerve transection and lumbar sympathectomy on galanin in lumbar dorsal root gangl ia (DRGs) was examined in mice overexpressing NGF (NGFOE) in the skin under the keratin promoter. The superior cervical ganglia (SCG) were also studie d. In the DRG pericellular baskets containing tyrosine hydroxylase- (TH) an d galanin-like immunoreactivity (LI) were found, mostly in the same fibers. Galanin-positive baskets were also found in the trigeminal ganglia. Howeve r, only single neuropeptide Y (NPY)-positive baskets were observed within t he DRGs, No marked difference in number of galanin-positive neurons was see n between wild-type and NGFOE mice. After sciatic nerve transection galanin was upregulated in DRG neurons to about the same extent in NGFOE mice as i n wild-type mice. Galanin-, but not TH-LIs decreased in the pericellular ba skets. After lumbar sympathectomy both galanin- and TH-immunoreactive baske ts disappeared, suggesting a sympathetic origin. In the SCG the very low ga lanin mRNA levels were strongly increased after lesion of the carotid nerve s, both in wild-type and in NGFOE mice. However, whereas NPY mRNA levels de creased in the SCG after axotomy in the wild-type mice, there was a distinc t increase in the NGFOE mice. Our results show that high NGF levels in skin induce formation of pericellular baskets in DRGs expressing galanin- and T H-LI and that galanin in these baskets is strongly influenced by peripheral axotomy, However, overexpression of NGF did not markedly influence galanin expression in DRG neurons, neither normally nor after nerve lesions. Final ly, expression of NPY in sympathetic ganglia is differently regulated in NG ;FOE compared to wild-type mice. (C) 2001 Academic Press.