The effect of Am-80, a synthetic retinoid, on spinal cord injury-induced motor dysfunction in rats.
The present study investigated the effect of 4[(5,6,7,8-tetrahydro-5,5,8,8,-tetramethyl-2-naphthalenyl)carbamoyl] benzoic acid (Am-80), a synthetic retinoid, on spinal cord injury (SCI) in rats. Treatment with Am-80 (orally and subcutaneously) significantly promoted recovery from SCI-induced motor dysfunction. On day 28 after injury, the lesion cavity was markedly reduced, while the expression of myelin basic protein (MBP; myelin), betaIIItubulin (neuron), and glial fibrillary acidic protein (GFAP; astrocyte) was increased, in comparison with SCI controls. Interestingly, expression of neurotrophin receptor, tyrosine kinase B (TrkB) was over 3-fold higher after Am-80 treatment than in SCI controls. A lot of TrkB-positive cells as well as brain-derived neurotrophic factor (BDNF)-positive ones were observed around the injured site. Am-80 (10 microM) combined with BDNF (100 ng/ml) promoted extensive neurite outgrowth and TrkB gene expression by cultured SH-SY5Y cells, as did all-trans retinoic acid (ATRA). Thymidine incorporation was dramatically suppressed, but there was little effect on cell viability. These findings suggest that Am-80 has the potential to be used for treating neurodegenerative disorders, including SCI. Its efficacy may be partly ascribed to promotion of cell viability and differentiation of neural stem cells through increased TrkB expression.
Takenaga
Mitsuko
M
Institute of Medical Science, St. Marianna University School of Medicine, Kawasaki, Japan. m2take@marianna-u.ac.jp
Ohta
Yuki
Y
Tokura
Yukie
Y
Hamaguchi
Akemi
A
Shudo
Koichi
K
Okano
Hideyuki
H
Igarashi
Rie
R
D000818:Animals; D001565:Benzoates / Q000494:pharmacology*; D015415:Biomarkers; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D005260:Female; D006614:Hindlimb / Q000294:innervation / Q000502:physiology; D006801:Humans; D007641:Keratolytic Agents / Q000494:pharmacology; D008124:Locomotion / Q000187:drug effects; D009069:Movement Disorders / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D009474:Neurons / Q000187:drug effects / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D012176:Retinoids / Q000494:pharmacology*; D013119:Spinal Cord Injuries / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D014212:Tretinoin / Q000494:pharmacology
D001565:Benzoates; D015415:Biomarkers; D007641:Keratolytic Agents; D009419:Nerve Tissue Proteins; D012176:Retinoids; D013764:Tetrahydronaphthalenes; C061133:tamibarotene; D014212:Tretinoin