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

GONZÁLEZ DENISELLE, M.C.; GRILLO C; GONZÁLEZ S.L; ROIG P; DE NICOLA A. F.

BRAIN RESEARCH

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 1999 vol. 841 p. 78 - 84

0006-8993

Expression of the growth-associated protein GAP-43 is increased in the spinal 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 mice was sensitive to steroid treatment. A group of control and wr mice received s.c. a 50 mg pellet of the natural hormone corticosterone CORT. or the antioxidant 21-aminosteroid U-74389F during 4 days. Basal levels of GAP-43 mRNA were 10-fold elevated in ventral horn motoneurons of untreatedwr mice, compared to the low levels in controls. The high expression of GAP-43 mRNA in wr was attenuated by treatment with CORT 41%, p-0.001. and U-74389F 36%, p-0.001.. Although specific GAP-43 mRNA labelling was present in some neurons around thecentral canal, its cellular expression was similar in controls and wr. Also, steroid treatment was ineffective in neurons around the central canal. Other regions of the spinal cord i.e., dorsal horn neurons. expressed GAP-43 mRNA slightly above background levels. It ispossible that attenuation of GAP-43 expression due to the natural hormone and the antioxidant steroid resulted from reversal of motoneuron degeneration or aberrant sprouting. Therefore, steroid therapy may be of value to prevent denervation andror muscularatrophy in this animal model.