Glucocorticoid receptors and actions in the spinal cord of the Wobbler mouse, a model for neurodegeneration

GONZÁLEZ DENISELLE, M.C.; GONZÁLEZ S.L; PIROLI G; FERRINI M; LIMA A; DE NICOLA A. F.

JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY

PERGAMON-ELSEVIER SCIENCE LTD

Año: 1997 vol. 60 p. 205 - 213

0960-0760

We have studied glucocorticoid receptors (GR) and actions in the spinal cord of the Wobbler mouse, a model for amyotrophic lateral sclerosis and infantile spinal muscular atrophy. Basal and stress levels of circulatig corticosterone (CORT) were increased in Wobbler mice. Single point binding assays showed that cytosolic type II GR in the spinal cord of Wobbler mice of both sexes were slighlty reduced compared with normal littermates. Saturation analysis further demonstrated a non-significant reduction in Bmax with increased Kd. In the hippocampus, however, we found downregulation of GR, a probable response to increased CORT levels. We also found that the basal activity of ornithine decarboxylase (ODC), a rate-limiting enzyme of polyamine biosynthesis, was higher in Wobbler mice than in control animals. Both groups showed a two-fold stimulation of ODC activity after treatment with dexamethasone (DEX). Additionally, Wobbler mice presented with an intense proliferation of astrocytes immunoreactive (ir) for glial fibrillary acidic protein (GFAP) in grey and white matter of the spinal cord. The enhanced GFAP-ir was attenuated after four days of treatment with a corticosterone (CORT) pellet implant, producing a pharmacological increase in peripheral circulating CORT. Taking into consideration the content of GR and thechanges in ODC activity and GFAP-ir brought about by glucocorticoids, we suggest that Wobbler mice are hormone responsive. Further elucidation of glucocorticoid effects in this model may be relevant for understanding the possible use of hormones in human neurodegenerative diseases. © 1997Elsevier Science Ltd.