The 21-Aminosteroid U-74389F increases the number of glial acidic protein-expressing astrocytes in the spinal cord of control and wobbler mice.

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

CELLULAR AND MOLECULAR NEUROBIOLOGY.

SPRINGER/PLENUM PUBLISHERS

Lugar: New York; Año: 1996 vol. 16 p. 61 - 72

0272-4340

Wobbler mice suffer an autosomal recessive mutation producing severemotoneuron degeneration and dense astrogliosis, with increased levels of glialfibrillary acidic protein (GFAP) in the spinal cord and brain stem. They havebeen considered animal models of amyotrophic lateral sclerosis and infantilespinal muscular atrophy.2. Using Wobbler mice and normal littermates, we investigated the effects ofthe membrane-active steroid Lazaroid U-74389F on the number of GFAPexpressingastrocytes and glucocorticoid receptors (GR). Lazaroids are inhibitorsof oxygen radical-induced lipid peroxidation, and proved beneficial in cases ofCNS injury and ischemia.3. Four days after pellet implantation of U-74389F into Wobbler mice,hyperplasia and hypertophy of GFAP-expressing astrocytes were apparent in thespinal cord ventral and dorsal horn, areas showing already intense astrogliosis inuntreated Wobbler mice. In control mice, U-74389F also produced astrocytehyperplasia and hypertophy in the dorsal horn and hyperplasia in the ventrallateralfuniculi of the cord.4. Given in vivo U-74389F did not change GR in spinal cord of Wobbler orcontrol mice, in line with the concept that it is active in membranes but does notbind to GR. Besides, U-74390F did not compete for [3H]dexamethasone bindingwhen added in vitro.5. The results suggest that stimulation of proliferation and size of GFAPexpressingastrocytes by U-74389F may be a novel mechanism of action of thiscompound. The Wobbler mouse may be a valuable animal model for furtherpharmacological testing of glucocorticoid and nonglucocorticoid steroids inneurodegenerative diseases.