Stimulated neuronal expression of brain-derived neurotrophic factor by Neurotropin.
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 10mNU/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 (200NU/kg/day, 3months) 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.
Fukuda
Yu
Y
Department of Neurology, Fujita Health University School of Medicine, Kutsukake-cho, Toyoake 470-1192, Japan.
Berry
Thomas L
TL
Nelson
Matthew
M
Hunter
Christopher L
CL
Fukuhara
Koki
K
Imai
Hideki
H
Ito
Shinji
S
Granholm-Bentley
Ann-Charlotte
AC
Kaplan
Allen P
AP
Mutoh
Tatsuro
T
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004314:Down Syndrome / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008297:Male; D008568:Memory / Q000187:drug effects; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009447:Neuroblastoma / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D011134:Polysaccharides / Q000494:pharmacology*; D011817:Rabbits; D020813:Receptor, trkB / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D011134:Polysaccharides; C010491:neurotropin; D020813:Receptor, trkB; D020928:Mitogen-Activated Protein Kinases