Evidence for down-regulation of GAP-43 mRNA in Wobbler mouse spinal motoneurons by corticosterone and a 21-aminosteroid

Expression of the growth-associated protein GAP-43 is increased in the spin al cord of ALS patients and Wobbler (wr) mice, murine models of the disease . In this work we examined if expression of GAP-43 mRNA in control and wr m ice was sensitive to steroid treatment. A group of control and wr mice rece ived s.c. a 50 mg pellet of the natural hormone corticosterone (CORT) or th e antioxidant 21-aminosteroid U-74389F during 4 days. Basal levels of GAP-4 3 mRNA were 10-fold elevated in ventral horn motoneurons of untreated wr mi ce, compared to the low levels in controls. The high expression of GAP-43 m RNA in wr was attenuated by treatment with CORT (41%, p < 0.001) and U-7438 9F (36%, p < 0.001). Although specific GAP-43 mRNA labelling was present in some neurons around the central canal, its cellular expression was similar in controls and wr. Also, steroid treatment was ineffective in neurons aro und the central canal. Other regions of the spinal cord (i.e., dorsal horn neurons) expressed GAP-43 mRNA slightly above background levels. It is poss ible that attenuation of GAP-43 expression due to the natural hormone and t he antioxidant steroid resulted from reversal of motoneuron degeneration or aberrant sprouting. Therefore, steroid therapy may be of value to prevent denervation and/or muscular atrophy in this animal model. (C) 1999 Elsevier Science B.V. All rights reserved.