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 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 untreated wr 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 the central 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 is possible 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 and/or muscular atrophy in this animal model.
González Deniselle
M C
MC
Department of Biochemistry, Faculty of Medicine, University of Buenos Aires, Argentina.
Grillo
C A
CA
González
S
S
Roig
P
P
De Nicola
A F
AF
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D003345:Corticosterone / Q000494:pharmacology*; D005260:Female; D019922:GAP-43 Protein / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008818:Mice, Neurologic Mutants; D009046:Motor Neurons / Q000378:metabolism*; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism; D011281:Pregnatrienes / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D013116:Spinal Cord / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects
D000975:Antioxidants; D019922:GAP-43 Protein; D011281:Pregnatrienes; D012333:RNA, Messenger; C074965:U 74389F; D003345:Corticosterone