Neurotrophin-3 reverses experimental cisplatin-induced peripheral sensory neuropathy.
Cisplatin, a widely used chemotherapeutic agent, induces a sensory neuropathy with selective loss of vibration sense and proprioception. Here we demonstrate that neurotrophin-3 (NT-3), a member of the nerve growth factor family of neurotrophic factors, restored to normal levels the reduced H-reflex-related sensory nerve conduction velocity induced by cisplatin in rats. NT-3 treatment corrected an abnormal cytoplasmic distribution of neurofilament protein in large sensory neurons in dorsal root ganglia and the reduction in the numbers of myelinated fibers in sural nerves caused by cisplatin. The NT-3-dependent reversal of cisplatin neurotoxicity thus suggests the possible use of NT-3 in the treatment of peripheral sensory neuropathy.
Gao
W Q
WQ
Department of Neuroscience, Genentech Inc, South San Francisco, CA 94080, USA.
Dybdal
N
N
Shinsky
N
N
Murnane
A
A
Schmelzer
C
C
Siegel
M
M
Keller
G
G
Hefti
F
F
Phillips
H S
HS
Winslow
J W
JW
D000818:Animals; D002945:Cisplatin / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects / Q000502:physiology; D006181:H-Reflex / Q000187:drug effects / Q000502:physiology; D007150:Immunohistochemistry; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology; D020933:Neurotrophin 3; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar
D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D002945:Cisplatin