Anatomical evidence supporting the potential for modulation by multiple neurotrophins in the majority of adult lumbar sensory neurons

Neurotrophins exert effects on sensory neurons through receptor tyrosine ki nases (trks) and a common neurotrophin receptor (p75). Quantitative in situ hybridization studies were performed on serial sections to identify neuron s expressing single or multiple neurotrophin trk receptor mRNA(s) in adult lumbar dorsal root ganglion (DRG) in order to examine the possibility of mu lti-neurotrophin modulation of phenotype via different trk receptors or var ious trk isoforms. Expression of mRNA encoding trkA, trkB, trkC, or p75 is restricted to select subpopulations representing approximately 41%, 33%, 43 %, and 79% of DRG neurons, respectively. Colocalization studies reveal that approximately 10% of DRG neurons coexpress trkA and trkB mRNA; 19% coexpre ss trkA and trkC mRNA; and 18% coexpress trkB and trkC mRNA. Trilocalizatio n of all three trk mRNAs is rare, with approximately 3-4% of neurons in thi s category. Overall incidence of expression of more than one full length tr k mRNA occurs in approximately 40% of DRG neurons, whereas expression of in dividual trk mRNA is found in approximately 34%. Full length trk receptor m RNA is rarely detected without p75, implicating the latter in neuronal resp onse to neurotrophins. Examination of two full-length isoforms of trkA reve al that they are coexpressed with relative levels of expression positively correlated. TrkC mRNAs corresponding to 14- or 39-amino acid insert isoform s colocalize with the non-insert trkC isoform, but the converse is not nece ssarily true. The data suggest that substantial subpopulations of adult sen sory neurons may be modulated through interactions with multiple neurotroph ins, the consequences of which are largely unknown. (C) 1999 Wiley-Liss, In c.