Neurosteroid progesterone is up-regulated in the brain of jimpy and shiverer mice

Concentrations of neurosteroids have been measured in the brains of postnat al myelin mutants jimpy (jp) and shiverer (shi) mice and of their normal co ntrols. Progesterone (PROG) concentrations were increased more than threefo ld in the brains of mutant mice. Marked astroglial reaction occurs in the b rains of jp mice and to a much smaller extent in shi ones. Whereas the mito chondrial benzodiazepine/diazepam binding inhibitor (DBI) receptor (MBR) wa s below the immunohistochemical detection limit in normal mice (except in t he choroid plexus and ependyma cells), it was significantly expressed in ma ny reactive astrocytes of jp and shi mice brains. DBI-like peptides, invest igated either by immunohistochemistry or by radioimmunoassay, were expresse d to similar extents in mutant and control mice. Reversed-phase HPLC indica ted that DBI-like peptides were almost exclusively of the triakontatetraneu ropeptide size. It was concluded that the increased expression of MBR (invo lved in the intramitochondrial delivery of cholesterol to P450scc) likely a ccounts for the large FROG content in mutant mice brain. The role of FROG i n myelin repair is discussed. GLIA 29:14-24, 2000. (C) 2000 Wiley-Liss, Inc .