Stimulated neuronal expression of brain-derived neurotrophic factor by Neurotropin

Yu Fukuda, Thomas L. Berry, Matthew Nelson, Christopher L. Hunter, Koki Fukuhara, Hideki Imai, Shinji Ito, Ann Charlotte Granholm-Bentley, Allen P. Kaplan, Tatsuro Mutoh

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)


Expression of brain-derived neurotrophic factor (BDNF) was stimulated in human neuroblastoma SH-SY5Y cells by a nonprotein extract of inflamed rabbit skin inoculated with vaccinia virus (Neurotropin®), an analgesic widely used in Japan for treatment of disorders associated with chronic pain, with the optimal dosage at 10. mNU/mL. This stimulation was accompanied by activations of p42/44 MAP kinase, CREB and c-Fos expression. Inhibitors of MAP kinases or PI 3-kinase prevented the stimulatory action of Neurotropin, indicating that neuronal TrkB/CREB pathway mediates the action. Repetitive oral administration of Neurotropin (200. NU/kg/day, 3. months) prevented the age-dependent decline in hippocampal BDNF expression in Ts65Dn mice, a model of Down's syndrome. This effect was associated with the improvement of spatial cognition of the mice. These results open an intriguing new strategy in which Neurotropin may prove beneficial treatment for neurodegenerative disorders.

Original languageEnglish
Pages (from-to)226-233
Number of pages8
JournalMolecular and Cellular Neuroscience
Issue number3
Publication statusPublished - 11-2010

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology


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