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Abstract:

The wobbler mouse suffers an autosomal recessive mutation producing severe neurodegeneration and astrogliosis in spinal cord. It has been considered a model for amyotrophic lateral sclerosis. We have studied in these animals the expression of two proteins, the growth-associated protein (GAP-43) and the NADPH-diaphorase, the nitric oxide synthesizing enzyme, employing immunocytochemistry and histochemistry. We found higher expression of GAP-43 immunoreactivity in dorsal horn, Lamina X, corticospinal tract and ventral horn motoneurons in wobbler mice compared to controls. We NADPH- diaphorase activity was present in control motoneurons, in contrast to intense labeling of the wobbler group. No differences in diaphorase activity was measured in the rest of the spinal cord between control and mutant mice. A group of animals received subcutaneously for 4 days a 50 mg pellet of U- 74389F, a glucocorticoid-derived 21-aminosteroid with antioxidant properties but without glucocorticoid activity. U-74389F slightly attenuated GAP-43 immunostaining in dorsal regions of the spinal cord from wobblers but not in controls. However, in motoneurons of wobbler mice number of GAP-43 immunopositive neurons, cell processes and reaction intensity were reduced by U-74389F. The aminosteroid reduced by 50% motoneuron NADPH-diaphorase activity. Hyperexpression of GAP-43 immunoreactivity in wobbler mice may represent an exaggerated neuronal response to advancing degeneration or muscle denervation. It may also be linked to increased nitric oxide levels. U-74389F may stop neurodegeneration and/or increase muscle trophism and stop oxidative stress, consequently GAP-43 hyperexpression was attenuated. Wobbler mice may be important models to evaluate the use of antioxidant steroid therapy with a view to its use in human motoneuron disease.

Registro:

Documento: Artículo
Título:The 21-aminosteroid U-74389F attenuates hyperexpression of GAP-43 and NADPH-diaphorase in the spinal cord of wobbler mouse, a model for amyotrophic lateral sclerosis
Autor:González Deniselle, M.C.; González, S.L.; Lima, A.E.; Wilkin, G.; De Nicola, A.F.
Filiación:Lab. of Neuroendocrine Biochemistry, Inst. de Biol. y Med. Experimental, Buenos Aires, Argentina
Dept. of Biochemistry, Wolfson Laboratories, Imp. Coll. Sci., Technol. and Med., Kensington, London, United Kingdom
Inst. Univ. de Ciencias de la Salud, Fundación Barceló, Buenos Aires, Argentina
Lab. of Neuroendocrine Biochemistry, Inst. de Biol. y Med. Experimental, Obligado 2490, 1428 Buenos Aires, Argentina
Palabras clave:21-aminosteroids; GAP-43; NADPH-diaphorase; Neurogeneration; Wobbler mouse; 21 [4 [2,6 bis(1 pyrrolidinyl) 4 pyrimidinyl] 1 piperazinyl]pregna 1,4,9(11) triene 3,20 dione; 21 aminosteroid; neuromodulin; reduced nicotinamide adenine dinucleotide phosphate dehydrogenase; amyotrophic lateral sclerosis; animal experiment; animal model; article; controlled study; drug effect; enzyme inhibition; glia cell; immunocytochemistry; motoneuron; mouse; nerve fiber regeneration; nerve sprouting; nonhuman; oxidative stress; priority journal; protein expression; spinal cord; Amyotrophic Lateral Sclerosis; Animals; Antioxidants; Dihydrolipoamide Dehydrogenase; Disease Models, Animal; Female; GAP-43 Protein; Gene Expression Regulation; Humans; Male; Mice; Mice, Neurologic Mutants; Motor Neurons; Pregnatrienes; Spinal Cord; Animalia
Año:1999
Volumen:24
Número:1
Página de inicio:1
Página de fin:8
DOI: http://dx.doi.org/10.1023/A:1020918310281
Título revista:Neurochemical Research
Título revista abreviado:Neurochem. Res.
ISSN:03643190
CODEN:NERED
CAS:Antioxidants; Dihydrolipoamide Dehydrogenase, EC 1.8.1.4; GAP-43 Protein; Pregnatrienes; U 74389F, 111668-89-4
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03643190_v24_n1_p1_GonzalezDeniselle

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Citas:

---------- APA ----------
González Deniselle, M.C., González, S.L., Lima, A.E., Wilkin, G. & De Nicola, A.F. (1999) . The 21-aminosteroid U-74389F attenuates hyperexpression of GAP-43 and NADPH-diaphorase in the spinal cord of wobbler mouse, a model for amyotrophic lateral sclerosis. Neurochemical Research, 24(1), 1-8.
http://dx.doi.org/10.1023/A:1020918310281
---------- CHICAGO ----------
González Deniselle, M.C., González, S.L., Lima, A.E., Wilkin, G., De Nicola, A.F. "The 21-aminosteroid U-74389F attenuates hyperexpression of GAP-43 and NADPH-diaphorase in the spinal cord of wobbler mouse, a model for amyotrophic lateral sclerosis" . Neurochemical Research 24, no. 1 (1999) : 1-8.
http://dx.doi.org/10.1023/A:1020918310281
---------- MLA ----------
González Deniselle, M.C., González, S.L., Lima, A.E., Wilkin, G., De Nicola, A.F. "The 21-aminosteroid U-74389F attenuates hyperexpression of GAP-43 and NADPH-diaphorase in the spinal cord of wobbler mouse, a model for amyotrophic lateral sclerosis" . Neurochemical Research, vol. 24, no. 1, 1999, pp. 1-8.
http://dx.doi.org/10.1023/A:1020918310281
---------- VANCOUVER ----------
González Deniselle, M.C., González, S.L., Lima, A.E., Wilkin, G., De Nicola, A.F. The 21-aminosteroid U-74389F attenuates hyperexpression of GAP-43 and NADPH-diaphorase in the spinal cord of wobbler mouse, a model for amyotrophic lateral sclerosis. Neurochem. Res. 1999;24(1):1-8.
http://dx.doi.org/10.1023/A:1020918310281