Beta-nerve growth factor gene therapy alleviates pyridoxine-induced neuropathic damage by increasing doublecortin and tyrosine kinase A in the dorsal root ganglion

초록

Beta-nerve growth factor (beta-NGF) is known to be a major leading cause of neuronal plasticity. To identify the possible action mechanisms of beta-NGF gene therapy for sciatic nerve recovery, experimental dogs were randomly divided into control, pyridoxine, and pyridoxine + beta-NGF groups. We observed chronological changes of morphology in the dorsal root ganglia in response to pyridoxine toxicity based on cresyl violet staining. The number of large neurons positive for cresyl violet was dramatically decreased after pyridoxine intoxication for 7 days in the dorsal root ganglia and the neuron number was gradually increased after pyridoxine withdrawal. In addition, we also investigated the effects of beta-NGF gene therapy on neuronal plasticity in pyridoxine-induced neuropathic dogs. To accomplish this, tyrosine kinase receptor A (TrkA), beta III-tubulin and doublecortin (DCX) immunohistochemical staining was performed at 3 days after the last pyridoxine treatment. TrkA-immunoreactive neurons were dramatically decreased in the pyridoxine group compared to the control group, but strong TrkA immunoreactivity was observed in the small-sized dorsal root ganglia in this group. TrkA immunoreactivity in the dorsal root ganglia was similar between beta-NGF and control groups. The numbers of beta III-tubulin- and DCX-immunoreactive cells decreased significantly in the pyridoxine group compared to the control group. However, the reduction of beta III-tubulin- and DCX-immunoreactive cells in the dorsal root ganglia in the beta-NGF group was significantly ameliorated than that in the pyridoxine group. These results indicate that beta-NGF gene therapy is a powerful treatment of pyridoxine-induced neuropathic damage by increasing the TrkA and DCX levels in the dorsal root ganglia.

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