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.

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.

Age-dependent changes in the nervous and endocrine control of the thymus.

The immune system, especially the thymus, undergoes age-related modifications leading to structural and functional changes in the lymphoid organs and immunocompetent cells. Nevertheless, the consequences of thymic involution in the peripheral pool of T-cells are still a matter of controversy. The control of the thymic function is very complex and involves intrathymic signals, the autonomic nervous system, and the endocrine system. Both thymocytes and thymic stromal cells express receptors for a wide range of hormones, as well as for neurotransmitters and neuropeptides, thus affecting thymocytes maturation. This review summarizes the age-dependent variations in the extrathymic components of the thymic microenvironment, i.e., vegetative nerves and hormones, and the possible effects of those changes in the immune function.