Neural Regeneration Research ›› 2020, Vol. 15 ›› Issue (1): 162-168.doi: 10.4103/1673-5374.264472

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

Hyun-Kee Cho1, Woosuk Kim2, Kwon-Young Lee3, Jin-Ok Ahn1, Jung Hoon Choi3, In Koo Hwang2, Jin-Young Chung1   

  1. 1 Department of Veterinary Internal Medicine and Institute of Veterinary Science, College of Veterinary Medicine, Kangwon National University, Chuncheon, Kangwon-do, South Korea
    2 Department of Anatomy and Cell Biology, College of Veterinary Medicine, Research Institute for Veterinary Science, Seoul National University, Seoul, South Korea
    3 Department of Anatomy, College of Veterinary Medicine, Kangwon National University, Chuncheon, Kangwon-do, South Korea
  • Online:2020-01-15 Published:2020-05-22
  • Contact: In Koo Hwang, DVM, PhD,vetmed2@snu.ac.kr; Jin-Young Chung, DVM, PhD,chungjinyoung@kangwon.ac.kr.
  • Supported by:
    This work was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by
    the Ministry of Science, ICT & Future Planning (No. NRF-2017R1A1A1A05000762) and by Cooperative Research Program for Agriculture Science and Technology Development, Rural Development Administration, Republic of Korea (No. PJ01395602; both to JYC).

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Abstract: Beta-nerve growth factor (β-NGF) is known to be a major leading cause of neuronal plasticity. To identify the possible action mechanisms of β-NGF gene therapy for sciatic nerve recovery, experimental dogs were randomly divided into control, pyridoxine, and pyridoxine + β-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 β-NGF gene therapy on neuronal plasticity in pyridoxine-induced neuropathic dogs. To accomplish this, tyrosine kinase receptor A (TrkA), βIII-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 β- NGF and control groups. The numbers of βIII-tubulin- and DCX-immunoreactive cells decreased significantly in the pyridoxine group compared to the control group. However, the reduction of βIII-tubulin- and DCX-immunoreactive cells in the dorsal root ganglia in the β-NGF group was significantly ameliorated than that in the pyridoxine group. These results indicate that β-NGF gene therapy is a powerful treatment of pyridoxine-induced neuropathic damage by increasing the TrkA and DCX levels in the dorsal root ganglia. The experimental protocol was approved by the Institutional Animal Care and Use Committee (IACUC) of Seoul National University, South Korea (approval No. SNU-060623-1, SNU-091009-1) on June 23, 2006 and October 9, 2009, respectively.

Key words: β-nerve growth factor, βIII-tubulin, doublecortin, gene therapy, neuron-glial antigen 2, neuropathy, pyridoxine