Glial cell line‐derived neurotrophic factor (GDNF) from adult rat tooth serves a distinct population of large‐sized trigeminal neurons

Abstract

Glial cell line-derived neurotrophic factor (GDNF) mediates trophic effects for specific classes of sensory neurons. The adult tooth pulp is a well-defined target of sensory trigeminal innervation. Here we investigated potential roles of GDNF in the regulation of adult trigeminal neurons and the dental pulp nerve supply of the rat maxillary first molar. Western blot analysis and radioactive 35S-UTP in situ hybridization revealed that GDNF in the dental pulp and its mRNAs were localized with Ngf in the coronal pulp periphery, in particular in the highly innervated subodontoblast layer. Retrograde neuronal transport of iodinated GDNF and Fluorogold (FG) from the dental pulp indicated that GDNF was transported in about one third of all the trigeminal dental neurons. Of the GDNF-labelled neurons, nearly all (97%) were large-sized (> or =35 microm in diameter). Analysis of FG-labelled neurons revealed that, of the trigeminal neurons supporting the adult dental pulp, approximately 20% were small-sized, lacked isolectin B4 binding and did not transport GDNF. Of the large-sized dental trigeminal neurons approximately 40% transported GDNF. About 90% of the GDNF-accumulating neurons were negative for the high-temperature nociceptive marker VRL-1. Our results show that a subclass of large adult trigeminal neurons are potentially dependent on dental pulp-derived GDNF while small dental trigeminal neurons seems not to require GDNF. This suggests that GDNF may function as a neurotrophic factor for subsets of nerves in the tooth, which apparently mediate mechanosensitive stimuli. As in dorsal root ganglia both small- and large-sized neurons are known to be GDNF-dependent; these data provide molecular evidence that the sensory supply in the adult tooth differs, in some aspects, from the cutaneous sensory system.

Projection of Non-peptidergic Afferents to Mouse Tooth Pulp

“…Using this approach, we found that pulpal afferents were 2.5% GFPpositive in mice. This confirms the results from the studies in rats reporting a rare population of IB4-positive pulpal afferents identified by approaches similar to those used in the current study (Fried et al, 1989;Yang et al, 2002;Kvinnsland et al, 2004;Gibbs et al, 2011).…”

“…The extent of the proportion of IB4-positive pulpal afferents in retrogradely labeled pulpal afferents is controversial. In rats, labeling of IB4 in TG sections showed that less than 5% of retrogradely labeled dental afferents are IB4-positive (Fried et al, 1989;Yang et al, 2002;Kvinnsland et al, 2004;Gibbs et al, 2011). In contrast, the percentages of IB4-positive pulpal afferents in cultured dental afferents were as high as 75% (Park et al, 2006;Kim et al, 2011).…”

Coordination of trigeminal axon navigation and patterning with tooth organ formation: epithelial-mesenchymal interactions, and epithelial Wnt4 and Tgfβ1 regulate semaphorin 3a expression in the dental mesenchyme

“…Our tissue recombination experiments showing that the E10.5 oral and E11 dental epithelia induce mesenchymal Sema3a expression indicate that, besides the odontogenic information, the presumptive dental epithelium also possesses the instructive information to control the formation of early tooth nerve supply and possible tooth-specific sensory innervation that is distinct, in some aspects, from the adjacent cutaneous sensory system (Fried et al, 2000;Kvinnsland et al, 2004). Furthermore, because the formation of teeth of all types is controlled by the epithelialmesenchymal interactions, the interactions also appear to provide a rationale for the fact that the timing and pattern of tooth innervation in different teeth and species correlate better to the developmental stage of the individual tooth than the chronological age of the animal.…”

Developmental changes in pulpal sensory innervation of rat incisors and molars shown on a single injection of the fluorescent dye AM1-43

“…Among these, nerve growth factor is a candidate for directing early pulp innervation in both incisors and molars because mice with a knockout of the trkA nerve growth factor receptor lack sensory nerves in the pulp of molars and incisors (Matsuo et al ., 2001). Glial cell line‐derived neurotrophic factor has also been shown to participate in dental pulp innervation (Luukko et al ., 1997; Kvinnsland et al ., 2004).…”