Expression of TrkB in the murine kidney.

Neurotrophins acting through Trk signal-transducing receptors play essential roles in the nervous system, and probably in some nonneuronal tissues. In the present study we used Western-blot and immunohistochemistry to investigate the occurrence and cellular localization of TrkB in the mouse kidney. Furthermore, the structure and ultrastructure of the kidney in mice carrying a mutation in the trkB gene were analyzed. TrkB in the kidney was identical to the cerebral one (145 kDa). Since the antibody used recognize a sequence within the tyrosine-kinase domain of TrkB, the renal TrkB receptor identified here must be regarded as able to mediate biological effects of their ligands. TrkB immunoreactivity was restricted to the juxtaglomerular apparatus, including differentiated vascular cells and extaglomerular mesangial cells. In these cells, TrkB colocalized with renin. The structural analysis revealed no major changes in the kidney structure of TrkB-deficient mice, with the exception of a significant reduction of the glomerular area. Nevertheless, in these animals there was an apparent increase in the number of extraglomerular mesangial cells (which retain the ability to synthesize renin) and absence of the macula densa. Taken together, these results strongly suggest a role of TrkB and their ligands in the control of the normal development and maintenance of the juxtaglomerular apparatus.

BDNF, but not NT-4, is necessary for normal development of Meissner corpuscles.

Meissner corpuscles are rapidly adapting cutaneous mechanoreceptors depending for development on TrkB expressing sensory neurons, but it remains to be established which of the known TrkB ligands, BDNF or NT-4, is responsible of this dependence. In this study we analyze Meissner corpuscles in the digital pads of mice with target mutations in the genes encoding for either BDNF or NT-4, using immunohistochemistry and transmission-electron microscopy, and they were identified based on their morphology and expression of S100 protein. All wild-type animals as well as NT-4(-/-) animals and BDNF and NT4 heterozygous animals have Meissner corpuscles that are normal in number and size. However, Meissner corpuscles are absent the BDNF(-/-) mice. These results suggest that BDNF is the only TrkB ligand involved in the development of Meissner corpuscles in murine glabrous skin, and it probably regulates the development of the sensory neurons that innervate Meissner corpuscles.

Absence of Meissner corpuscles in the digital pads of mice lacking functional TrkB.

The TrkB-expressing sensory neurons seem to be involved in touch and other discriminative sensibilities. Thus, several slowly and rapidly adapting cutaneous mechanoreceptors, as well as muscle spindles, are reduced or absent in the territory of the trigeminal nerve in functionally TrkB-deficient mice. Whether this also occurs in the cutaneous or muscular territories of dorsal root ganglia has not been analyzed. Here we used immunohistochemistry and transmission-electron microscopy to analyze the impact of a mutation in the gene coding for TrkB on Meissner and Pacinian corpuscles, and muscle spindles. The animals were studied at the post-natal days 15 and 25, because at this time all the mechanoreceptors examined are fully developed. Typical Meissner's corpuscles, displaying S-100 protein immunoreactivity, were found in the digital pads of wild-type and TrkB+/- mice whereas they were absent in the TrkB-/- animals. Regarding Pacinian corpuscles, the mutation in the trkB gene does not alter either the immunohistochemical or the ultrastructural characteristics. Finally, in muscle spindles the arrangement of the intrafusal muscle fibers and nerve fibers was unchanged in the mutated animals. Nevertheless, about 10% of muscle spindles showed increased number of the intrafusal cells (between 6 and 12) and were supplied by more than one large myelinic nerve fiber. The present results strongly suggest that TrkB-expressing sensory neurons in dorsal root ganglia, like those of the trigeminal ganglion, are responsible for the development and maintenance of several rapidly adapting cutaneous mechanoreceptors, i.e. Meissner's corpuscles.