Ultrastructural aspects of DRG satellite cell involvement in experimental cisplatin neuronopathy

Abstract

Different substances may induce neurological impairment, clinically expressed as peripheral neuropathies, due to damage of the neuronal bodies (neuronopathy) of sensory or motor neurons. Neuronopathies have generally been studied referring to neurons, although other cellular components may also be damaged. Cisplatin (CDDP) is known to be neurotoxic to the neurons of the dorsal root ganglia (DRG). The scarcity of information as to the possible involvement and role played by dorsal root ganglion (DRG) satellite cells in neuronopathies prompted this study using the chronic DRG neuronopathy induced by the repeated administration of CDDP in rats as a model. Eighteen female Wistar rats were treated according to 3 different schedules of CDDP administration (6 rats for each group). Six further animals were used as controls. At the end of the experiment the L4-L5-L6 dorsal root ganglia were examined at the light and electron microscope. Ag-NOR reaction was also examined in 4 further CDDP-treated rats and 4 controls. Pathological changes in satellite cells of animals treated with CDDP were remarkable in the nucleus where heterochromatin clumps were reduced or even completely absent. Morphometric analysis of the area occupied by heterochromatin indicated that this nuclear component decreased in an exposure-time dependent manner. Frequently, nucleolar-like structures became apparent in the nucleus of the rats treated with the higher doses of CDDP. Ag-NOR positive regions in the nuclei of treated rats were increased with respect to the controls. Cytoplasmic changes in DRG satellite cells of CDDP treated rats were limited, being characterized by an increased electron-density of the matrix. In treated rats deep invaginations between satellite cells and the neuronal surface were evident, leading to the formation of vacuoli. The interstitial connective space often showed edematous areas. Our observations demonstrate that in chronic cisplatin neuronopathy, DRG satellite cells are also involved in the pathological changes induced by drug exposure, and that these changes may be interpreted as being mainly reactive.