Mifepristone (RU 38486) influences expression of glycoprotein Po and morphological parameters at the level of rat sciatic nerve: in vivo observations.
The observations here reported indicate that, in vivo, the expression of an important protein of peripheral myelin, the glycoprotein Po, is influenced by mifespristone (RU 38486), that is, an antagonist of progesterone (PR) and glucocorticoid (GR) receptor. In our experimental model, male rats have been treated at the first day of life with this antagonist and after repeated treatments, we have analyzed in the sciatic nerve of 20- (20d) and 30-day-old rats (30d) the mRNA and protein levels of Po. Moreover, expression of Po has also been analyzed in the sciatic nerve of animals treated during the first 30 days of postnatal life and then sacrificed at 90th day of life (90d). The results obtained have indicated that both mRNA and protein levels of Po decrease at 20d. Apparently, these effects seem to be transient because no changes are evident at the other two times of analysis. As shown by morphometric analysis, the treatment with RU 38486 is also able to induce morphological changes at the level of sciatic nerve. However, at variance to what is expected by an alteration of an important component of the myelin membranes like Po, no changes are evident at the level of the myelin compartment. On the contrary, a significant reduction of axon diameter in parallel to an increase in neurofilament (NF) density occurs since 30d. In conclusion, the present data seem to suggest that progestin and/or glucocorticoid signals are not only involved in the control of myelin compartment but also on the axon maintenance.
Melcangi
R C
RC
Department of Endocrinology and Center of Excellence on Neurodegenerative Diseases, University of Milan, 20133 Milan, Italy. roberto.melcangi@unimi.it
Leonelli
E
E
Magnaghi
V
V
Gherardi
G
G
Nobbio
L
L
Schenone
A
A
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000648:ultrastructure; D015152:Blotting, Northern; D015153:Blotting, Western; D006727:Hormone Antagonists / Q000494:pharmacology*; D008297:Male; D008854:Microscopy, Electron; D015735:Mifepristone / Q000494:pharmacology*; D018993:Myelin P0 Protein / Q000096:biosynthesis* / Q000187:drug effects* / Q000648:ultrastructure; D009186:Myelin Sheath / Q000187:drug effects / Q000648:ultrastructure; D016900:Neurofilament Proteins / Q000187:drug effects / Q000648:ultrastructure; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects* / Q000648:ultrastructure
D006727:Hormone Antagonists; D018993:Myelin P0 Protein; D016900:Neurofilament Proteins; D012333:RNA, Messenger; D015735:Mifepristone