Neuropeptides and morphological changes in cisplatin-induced dorsal root ganglion neuronopathy.

Abstract:

:Dorsal root ganglia (DRG) neuronopathy was induced in rats by chronic treatment (2 mg/kg twice a week for nine injections) with the antineoplastic drug cisplatin. Morphological alterations and changes in peptide [calcitonin gene-related peptide (CGRP), substance P, galanin (Gal), and somatostatin] concentration were studied in the DRG, the spinal cord, and the sciatic nerve. Peptide concentration was increased in DRG neurons, with CGRP and Gal showing the highest increase. Conversely, in the sciatic nerve there was a general decrease in peptide content. In DRG a reduction in the nuclear, cytoplasmic, and nucleolar areas of primary sensory neurons was evident and was accompanied by clear-cut aspects of nucleolar structural damage. In peripheral nerves only extensive morphometric determinations could evidence a reduction in nerve conduction velocities and impairment in pain detection and coordination. Some of the nerve fibers presented axonal and adaxonal accumulations, suggesting the presence of an axonopathy. These results confirm that DRG cells are the primary target of cisplatin-induced neurotoxicity. Milder alterations can be detected in peripheral nerves. The increase in peptide concentration in DRG is probably due to cisplatin-related damage to the axonal transport system rather than to an increased synthesis.

journal_name

Exp Neurol

journal_title

Experimental neurology

authors

Barajon I,Bersani M,Quartu M,Del Fiacco M,Cavaletti G,Holst JJ,Tredici G

doi

10.1006/exnr.1996.0050

subject

Has Abstract

pub_date

1996-03-01 00:00:00

pages

93-104

issue

1

eissn

0014-4886

issn

1090-2430

pii

S0014-4886(96)90050-3

journal_volume

138

pub_type

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