title: Ro5-4864, a synthetic ligand of peripheral benzodiazepine receptor, reduces aging-associated myelin degeneration in the sciatic nerve of male rats.
abstract: The peripheral-type benzodiazepine receptor (PBR) is a protein predominantly located in the mitochondrial outer membrane that plays an important role in the regulation of cell survival and proliferation. Previous studies have shown an enhanced expression of PBR in the regenerating sciatic nerve, suggesting that this protein may be involved in the regenerative response. The rat sciatic nerve suffers important structural alterations with aging, including alterations in the morphology of myelin sheaths and a decrease in the number of myelinated fibers. In this study, we have assessed the effect of two PBR ligands, Ro5-4864 and PK-11195, to determine whether PBR may influence aging-associated morphological changes in the sciatic nerve. The treatment of 23-month-old, Sprague-Dawley male rats for 1 month with Ro5-4864 significantly reduced the percentage of fibers with myelin decompaction and increased the total number of myelinated fibers. In contrast, PK-11195, a PBR ligand that binds to a different site than Ro5-4864 in the PBR molecule, did not significantly affect any of the parameters analyzed. These findings support the potential role of PBR ligands to prevent aging-associated peripheral nerve degeneration.
authors.affiliation: Department of Endocrinology and Center of Excellence on Neurodegenerative Diseases, University of Milan, Via G. Balzaretti 9, 20133 Milano, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Leonelli
authors.forename: Josue G
authors.initials: JG
authors.lastname: Yague
authors.forename: Marinella
authors.initials: M
authors.lastname: Ballabio
authors.forename: Inigo
authors.initials: I
authors.lastname: Azcoitia
authors.forename: Valerio
authors.initials: V
authors.lastname: Magnaghi
authors.forename: Michael
authors.initials: M
authors.lastname: Schumacher
authors.forename: Luis Miguel
authors.initials: LM
authors.lastname: Garcia-Segura
authors.forename: Roberto Cosimo
authors.initials: RC
authors.lastname: Melcangi
mesh_terms: D000375:Aging / Q000473:pathology / Q000502:physiology*; D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology*; D002352:Carrier Proteins / Q000378:metabolism*; D008297:Male; D009186:Myelin Sheath / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D009410:Nerve Degeneration / Q000473:pathology / Q000503:physiopathology; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D012584:Sciatic Nerve / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure
chemical_list: D001570:Benzodiazepinones; D002352:Carrier Proteins; D011963:Receptors, GABA-A; C069997:Tspo protein, rat; C028513:4'-chlorodiazepam