tretinoin and Movement-Disorders

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.

Topics: Animals; Benzoates; Biomarkers; Blotting, Western; Cell Differentiation; Cell Line, Tumor; Female; Hindlimb; Humans; Keratolytic Agents; Locomotion; Movement Disorders; Nerve Tissue Proteins; Neurons; Rats; Rats, Sprague-Dawley; Retinoids; Spinal Cord Injuries; Tetrahydronaphthalenes; Tretinoin

The present study extends previous investigations examining the behavioral outcomes of all-trans retinoic acid (RA) exposure at embryonic (E) days 14-16. A sublethal dose (2.5 mg/kg b.w.) compatible with high neonatal survival sufficient to supply offspring for later behavioral testing, was used. The results show that E14-16 RA exposure, similar to E8-10 or E11-13 (previous studies), impairs locomotor activity (open field test) as well as motor coordination and motor learning (rotarod/accelerod task) in young-adult rats. The results provide further evidence that RA exposure induces a pattern of motor deficits which are not strictly related to the embryonic stage, compatible with the protracted developmental profile of the cerebellum.

Topics: Analysis of Variance; Animals; Animals, Newborn; Antineoplastic Agents; Body Weight; Escape Reaction; Female; Forelimb; Hand Strength; Motor Activity; Movement Disorders; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Sprague-Dawley; Reflex; Reproduction; Rotarod Performance Test; Statistics, Nonparametric; Tretinoin