Neurochemical Research, Vol. 21, No. 7, 1996, pp. 809-814 Neurotrophin-3 and TrkC-Immunoreactive Neurons in Rat Dorsal Root Ganglia Correlate by Distribution and Morphology* Colin Chen, ~ Xin-Fu Zhou, 1,2 and Robert A. Rush 1 (Accepted January 23, 1996) Previous studies have shown that a subpopulation of large dorsal root ganglion neurons contains neurotrophin-3 (NT3)-like immunoreactivity. It is not known, however, whether these NT3 im- munoreactive neurons also express the high affinity receptor for NT3, trkC. In the present study, the distribution and morphology of trkC immunoreactive neurons have been correlated with those of NT3 immunoreactive neurons in the dorsal root ganglia. Size and segmental distributions of both antigens indicate that they are present in the same group of large sensory neurons. Almost twice the number of these neurons are present in the cervical and lumbar spinal ganglia than in the thoracic. Co-localization study indicates that 94% of NT3 immunoreactive neurons express trkC. Our findings support the proposal that NT3 in these neurons is derived from their peripheral targets rather than synthesized in situ. KEY WORDS: Neurotrophin 3; TrkC; dorsal root ganglion; sensory neuron; immunohistochemistry. INTRODUCTION Neurons require neurotrophic factors for their sur- vival and growth. One family of neurotrophic factors, the neurotrophins, are a group of structurally related ba- sic proteins known to influence the development of many neuronal populations, including those of the dorsal root ganglia (DRG; 1). One member of this family, neu- rotrophin 3 (NT3), acts as a survival factor for a sub- population of sensory neurons both" in vitro (2,3) and in vivo (4-6). This action most likely is mediated by the high affinity, tyrosine kinase receptor, trkC (7,8). mRNA Department of Human Physiology and Centre for Neuroscience, Flin- ders University of South Australia, G.P.O. Box 2100, Adelaide 5001, Australia. 2 Address reprint requests to: Dr. Xin-Fu Zhou, Growth Factor Labo- ratory, Department of Human Physiology and Centre for Neurosei- ence, Flinders Medical Centre, G.P.O. Box 2100, Adelaide 5001, Australia. Tel: (618) 204 4408; e-mail: pzxfz@cc.flinders.edu.au. * Special issue dedicated to Dr. Hans Thoenen. 809 for both NT3 and trkC are present in developing DRG, but the level of NT3 mRNA declines in maturity to in- significant levels (9,10). Many large diameter neurons are capable of transporting ~2SI-labeled exogenous NT3 from the periphery to the cell soma (11) and are im- munoreactive for endogenous NT3 (12). NT3 mRNA has been detected biochemically within skeletal muscle and skin (13,14) and histochemically within muscle spindles (15,16). Mutant mice, created by deletion of either the NT3 or trkC gene, lack a significant number of sensory neurons and particularly those involved in proprioception (4,5,17). These findings suggest that en- dogenous NT3 is derived from peripheral tissues and is retrogradely transported within a subpopulation of sen- sory neurons to regulate neuronal metabolism. However, no attempt has yet been made to directly demonstrate the presence of NT3 in neurons synthesizing the trkC protein. In the present study, the distribution and mor- phology of trkC immunoreactive (-ir) neurons in the DRG have been correlated with those containing NT3 0364-3190/96/0700-0809509.50/0 9 1996Plenum Publishing Corporation