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

Isabella Barajon, Maurizio Bersani, Marina Quartu, Marina Del Fiacco, Guido Cavaletti, Jens Juul Holst, Giovanni Tredici

Research output: Contribution to journalArticle

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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 large myelinated fibers. Electrophysiological and behavioral studies evidenced 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.

Original languageEnglish
Pages (from-to)93-104
Number of pages12
JournalExperimental Neurology
Volume138
Issue number1
DOIs
Publication statusPublished - Mar 1996

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Spinal Ganglia
Neuropeptides
Cisplatin
Galanin
Peptides
Calcitonin Gene-Related Peptide
Sciatic Nerve
Peripheral Nerves
Axonal Transport
Neural Conduction
Sensory Receptor Cells
Substance P
Somatostatin
Nerve Fibers
Antineoplastic Agents
Spinal Cord
Neurons
Pain
Injections

ASJC Scopus subject areas

  • Neurology
  • Neuroscience(all)

Cite this

Barajon, I., Bersani, M., Quartu, M., Del Fiacco, M., Cavaletti, G., Holst, J. J., & Tredici, G. (1996). Neuropeptides and morphological changes in cisplatin-induced dorsal root ganglion neuronopathy. Experimental Neurology, 138(1), 93-104. https://doi.org/10.1006/exnr.1996.0050

Neuropeptides and morphological changes in cisplatin-induced dorsal root ganglion neuronopathy. / Barajon, Isabella; Bersani, Maurizio; Quartu, Marina; Del Fiacco, Marina; Cavaletti, Guido; Holst, Jens Juul; Tredici, Giovanni.

In: Experimental Neurology, Vol. 138, No. 1, 03.1996, p. 93-104.

Research output: Contribution to journalArticle

Barajon, I, Bersani, M, Quartu, M, Del Fiacco, M, Cavaletti, G, Holst, JJ & Tredici, G 1996, 'Neuropeptides and morphological changes in cisplatin-induced dorsal root ganglion neuronopathy', Experimental Neurology, vol. 138, no. 1, pp. 93-104. https://doi.org/10.1006/exnr.1996.0050
Barajon, Isabella ; Bersani, Maurizio ; Quartu, Marina ; Del Fiacco, Marina ; Cavaletti, Guido ; Holst, Jens Juul ; Tredici, Giovanni. / Neuropeptides and morphological changes in cisplatin-induced dorsal root ganglion neuronopathy. In: Experimental Neurology. 1996 ; Vol. 138, No. 1. pp. 93-104.
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