Distribution and colocalization of NGF and GDNF family ligand receptor mRNAs in dorsal root and nodose ganglion neurons of adult rats

Abstract

To understand the dependence of primary sensory neurons on neurotrophic factors, we examined the distribution and colocalization of mRNAs for receptors of nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF) family ligands in dorsal root ganglion (DRG) and nodose ganglion (NG) neurons of adult rats by in situ hybridization (ISH) histochemistry using serial sections. About 35, 10, and 20% of the lumbar DRG neurons expressed trkA, trkB and trkC mRNAs, respectively. Messenger RNA signals for c-ret, a common signaling receptor of GDNF family ligands, were seen in about 60% of DRG neurons, and some of these neurons expressed trkA, trkB, or trkC mRNAs. Most (97%) of the DRG neurons observed were positive to at least one of these four mRNAs. About 50, 20, and 20% of DRG neurons expressed GDNF family receptor α1 (GFR α1), GFR α2, and GFR α3 mRNAs, respectively, and most of these neurons were positive to c-ret mRNA. Interestingly, GFR α2 and GFR α3 mRNA signals were frequently seen in the same neurons, which lack GFR α1 mRNA signals. On the other hand, 98% of NG neurons expressed trkB mRNA and 30–40% of NG neurons co-expressed c-ret and GFR α1 mRNAs. However, mRNA signals for other receptors (TrkA, TrkC, GFR α2, GFR α3) were seen in only a few NG neurons. These findings suggest that all the DRG neurons in adult rats depend on at least one of the NGF and GDNF family ligands, and that some DRG neurons depend on two ligands or more. In contrast, NG neurons were suggested to be divided into two major groups; one group depends on brain-derived neurotrophic factor (BDNF)/neurotrophin-4/5 (NT-4/5), and the other depends on both BDNF/NT-4/5 and GDNF.