GLUCOCORTICOID RECEPTORS AND ACTIONS IN THE SPINAL-CORD OF THE WOBBLER MOUSE, A MODEL FOR NEURODEGENERATIVE DISEASES

We have studied glucocorticoid receptors (GR) and actions in the spina l cord of the Wobbler mouse, a model for amyotrophic lateral sclerosis and infantile spinal muscular atrophy. Basal and stress levels of cir culatig corticosterone (CORT) were increased in Wobbler mice. Single p oint binding assays showed that cytosolic type II GR in the spinal cor d of Wobbler mice of both sexes were slighlty reduced compared with no rmal Littermates. Saturation analysis further demonstrated a non-signi ficant reduction in B-max with increased K-d. In the hippocampus, howe ver, we found downregulation of GR, a probable response to increased C ORT levels. We also found that the basal activity of ornithine decarbo xylase (ODC), a rate-limiting enzyme of polyamine biosynthesis, was hi gher 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 proliferati on of astrocytes immunoreactive (ir) for glial fibrillary acidic prote in (GFAP) in grey and white matter of the spinal cord. The enhanced GF AP-ir was attenuated after four days of treatment with a corticosteron e (CORT) pellet implant, producing a pharmacological increase in perip heral circulating CORT. Taking into consideration the content of GR an d the changes in ODC activity and GFAP-ir brought about by glucocortic oids, we suggest that Wobbler mice are hormone responsive. Further elu cidation of glucocorticoid effects in this model may be relevant for u nderstanding the possible use of hormones in human neurodegenerative d iseases. (C) 1997 Elsevier Science Ltd.