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Neurotoxicity caused by didanosine on cultured dorsal root ganglion neurons

Cell Biology and Toxicology : Volume 23

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Neurotoxicity caused by didanosine on cultured dorsal root ganglion neurons

Content Provider	Springer Nature Link
Author	Liu, H. Liu, Z. Yang, X. Huang, F. Ma, C. Li, Z.
Copyright Year	2007
Abstract	The purpose of the present study was to investigate whether didanosine (ddI) directly causes morphological and ultrastructural abnormalities of dorsal root ganglion (DRG) neurons in vitro. Dissociated DRG cells and organotypic DRG explants from embryonic 15-day-old Wistar rats were cultured for 3 days and then exposed to ddI (1 μg/ml, 5 μg/ml, 10 μg/ml, and 20 μg/ml) for another 3 days and 6 days, respectively. Neurons cultured continuously in medium served as normal controls. The diameter of the neuronal cell body and neurite length were measured in dissociated DRG cell cultures. Neuronal ultrastructural changes were observed in both culture models. ddI induced dose-dependent decreases in neurite number, length of the longest neurite in each neuron, and total neurite length per neuron in dissociated DRG cell cultures with 3 days treatment. There were no morphological changes seen in organotypic DRG cultures even with longer exposure time (6 days). But ddI induced ultrastructural changes in both culture models. Ultrastructural abnormalities included loss of cristae in mitochondria, clustering of microtubules and neurofilaments, accumulation of glycogen-like granules, and emergence of large dense particles between neurites or microtubules. Lysosome-like large particles emerged inconstantly in neurites. ddI induced a neurite retraction or neurite loss in a dose-dependent manner in dissociated DRG neurons, suggesting that ddI may partially contribute to developing peripheral neuropathy. Cytoskeletal rearrangement and ultrastructural abnormalities caused by ddI in both culture models may have a key role in neurite degeneration.
Starting Page	113
Ending Page	121
Page Count	9
File Format	PDF
ISSN	07422091
Journal	Cell Biology and Toxicology
Volume Number	24
Issue Number	1
e-ISSN	15736822
Language	English
Publisher	Springer Netherlands
Publisher Date	2007-07-06
Publisher Place	Dordrecht
Access Restriction	Subscribed
Subject Keyword	Acquired immunodeficiency syndrome Didanosine Dorsal root ganglion Human immunodeficiency virus Neuropathy Biochemistry Pharmacology/Toxicology Cell Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Health, Toxicology and Mutagenesis Toxicology

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