Neurotoxicity caused by didanosine on cultured dorsal root ganglion neurons |
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Authors: | H Liu Z Liu X Yang F Huang C Ma Z Li |
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Institution: | (1) Department of Rheumatology, Shandong University Qilu Hospital, Jinan, China;(2) Department of Anatomy, Shandong University School of Medicine, 44 West Wenhua Road, Jinan, Shandong Province, 250012, China;(3) Department of Nephrology, Shandong University Qilu Hospital, Jinan, China;(4) Department of Immunology, Shandong University School of Medicine, Jinan, China |
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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. |
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Keywords: | Acquired immunodeficiency syndrome Didanosine Dorsal root ganglion Human immunodeficiency virus Neuropathy |
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