Evidence that nerve growth factor promotes the recovery of peripheral neuropathy induced in mice by cisplatin: behavioral, structural and biochemical analysis.
In this study we investigate the neurotoxic action of Cisplatin (6 micrograms/g body weight for 5 treatment cycles during 15 weeks with a total dose of 30 micrograms/g), an antitumor drug, and its effect on the level of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in peripheral tissues. We found that Cisplatin in adult rodents impairs peripheral sensory function and both sympathetic and sensory peripheral innervation as shown by the hot-plate response, catecholamine distribution and substance P immunoreactivity respectively. These changes are associated with decreased NGF in intestine, paws, and bladder while NGF increased in the spinal cord. Also BDNF decreased in bladder and paws and increased in spinal cord and intestine. To further investigate the role of NGF in the pathogenesis of Cisplatin-induced peripheral neuropathies a group of animals was injected with NGF (1 microgram/g every 4 days for 4 times) following Cisplatin treatment and evaluated for sensory function, sympathetic and sensory innervation and BDNF levels. Data demonstrated that exogenous NGF administration is able to restore biochemical, structural and functional changes induced by Cisplatin. These findings suggest that the reduction of NGF availability could be a cause of Cisplatin-induced peripheral neuropathies and that NGF exogenous administration could prevent or reduce Cisplatin neurotoxicity also in cancer patients, reducing the side effects of chemotherapy.
Institute of Neurobiology, Consiglio Nazionale delle Ricerche, Viale Marx, 15/43, 00137 Rome, Italy. aloe@in.rm.cnr.it
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Manni
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Properzi
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D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002945:Cisplatin / Q000633:toxicity*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D020932:Nerve Growth Factor / Q000378:metabolism* / Q000494:pharmacology*; D010147:Pain Measurement; D010525:Peripheral Nerves / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D013373:Substance P / Q000378:metabolism; D017779:Sympathetic Fibers, Postganglionic / Q000187:drug effects / Q000473:pathology
D000970:Antineoplastic Agents; D019208:Brain-Derived Neurotrophic Factor; D013373:Substance P; D020932:Nerve Growth Factor; D002945:Cisplatin