González Deniselle M C, González S, Piroli G, Ferrini M, Lima A E, De Nicola A F
Laboratory of Neuroendocrine Biochemistry, Instituto de Biología y Medicina Experimental-CONICET, Buenos Aires, Argentina.
J Steroid Biochem Mol Biol. 1997 Feb;60(3-4):205-13. doi: 10.1016/s0960-0760(96)00193-8.
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 circulating 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 slightly reduced compared with normal littermates. Saturation analysis further demonstrated a non-significant reduction in Bmax with increased Kd. In the hippocampus, however, we found down-regulation 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 the changes 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.
我们研究了摇摆小鼠脊髓中的糖皮质激素受体（GR）及其作用，该小鼠是肌萎缩侧索硬化症和婴儿脊髓性肌萎缩症的模型。摇摆小鼠循环皮质酮（CORT）的基础水平和应激水平均升高。单点结合试验表明，与正常同窝小鼠相比，两性摇摆小鼠脊髓中的胞质II型GR略有减少。饱和分析进一步表明，最大结合容量（Bmax）无显著降低，但解离常数（Kd）增加。然而，在海马体中，我们发现GR下调，这可能是对CORT水平升高的一种反应。我们还发现，多胺生物合成的限速酶鸟氨酸脱羧酶（ODC）的基础活性在摇摆小鼠中高于对照动物。两组在用地塞米松（DEX）处理后，ODC活性均有两倍的刺激。此外，摇摆小鼠脊髓灰质和白质中胶质纤维酸性蛋白（GFAP）免疫反应性（ir）的星形胶质细胞强烈增殖。在用皮质酮（CORT）丸植入物治疗四天后，增强的GFAP-ir减弱，导致外周循环CORT的药理学增加。考虑到GR的含量以及糖皮质激素引起的ODC活性和GFAP-ir的变化，我们认为摇摆小鼠对激素有反应。进一步阐明该模型中糖皮质激素的作用可能有助于理解激素在人类神经退行性疾病中的潜在用途。
