title: Effects of Nandrolone in the Counteraction of Skeletal Muscle Atrophy in a Mouse Model of Muscle Disuse: Molecular Biology and Functional Evaluation.
abstract: Muscle disuse produces severe atrophy and a slow-to-fast phenotype transition in the postural Soleus (Sol) muscle of rodents. Antioxidants, amino-acids and growth factors were ineffective to ameliorate muscle atrophy. Here we evaluate the effects of nandrolone (ND), an anabolic steroid, on mouse skeletal muscle atrophy induced by hindlimb unloading (HU). Mice were pre-treated for 2-weeks before HU and during the 2-weeks of HU. Muscle weight and total protein content were reduced in HU mice and a restoration of these parameters was found in ND-treated HU mice. The analysis of gene expression by real-time PCR demonstrates an increase of MuRF-1 during HU but minor involvement of other catabolic pathways. However, ND did not affect MuRF-1 expression. The evaluation of anabolic pathways showed no change in mTOR and eIF2-kinase mRNA expression, but the protein expression of the eukaryotic initiation factor eIF2 was reduced during HU and restored by ND. Moreover we found an involvement of regenerative pathways, since the increase of MyoD observed after HU suggests the promotion of myogenic stem cell differentiation in response to atrophy. At the same time, Notch-1 expression was down-regulated. Interestingly, the ND treatment prevented changes in MyoD and Notch-1 expression. On the contrary, there was no evidence for an effect of ND on the change of muscle phenotype induced by HU, since no effect of treatment was observed on the resting gCl, restCa and contractile properties in Sol muscle. Accordingly, PGC1α and myosin heavy chain expression, indexes of the phenotype transition, were not restored in ND-treated HU mice. We hypothesize that ND is unable to directly affect the phenotype transition when the specialized motor unit firing pattern of stimulation is lacking. Nevertheless, through stimulation of protein synthesis, ND preserves protein content and muscle weight, which may result advantageous to the affected skeletal muscle for functional recovery.
authors.affiliation: Section of Pharmacology, Dept. of Pharmacy & Drug Sciences, University of Bari "Aldo Moro", Bari, Italy.
authors.forename: Giulia Maria
authors.initials: GM
authors.lastname: Camerino
authors.affiliation: Section of Pharmacology, Dept. of Pharmacy & Drug Sciences, University of Bari "Aldo Moro", Bari, Italy.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Desaphy
authors.affiliation: Section of Pharmacology, Dept. of Pharmacy & Drug Sciences, University of Bari "Aldo Moro", Bari, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: De Bellis
authors.affiliation: Section of Pharmacology, Dept. of Pharmacy & Drug Sciences, University of Bari "Aldo Moro", Bari, Italy.
authors.forename: Roberta Francesca
authors.initials: RF
authors.lastname: Capogrosso
authors.affiliation: Section of Pharmacology, Dept. of Pharmacy & Drug Sciences, University of Bari "Aldo Moro", Bari, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Cozzoli
authors.affiliation: Section of Pharmacology, Dept. of Pharmacy & Drug Sciences, University of Bari "Aldo Moro", Bari, Italy.
authors.forename: Maria Maddalena
authors.initials: MM
authors.lastname: Dinardo
authors.affiliation: Section of Pharmacology, Dept. of Pharmacy & Drug Sciences, University of Bari "Aldo Moro", Bari, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Caloiero
authors.affiliation: Section of Pharmacology, Dept. of Pharmacy & Drug Sciences, University of Bari "Aldo Moro", Bari, Italy.
authors.forename: Kejla
authors.initials: K
authors.lastname: Musaraj
authors.affiliation: Section of Pharmacology, Dept. of Pharmacy & Drug Sciences, University of Bari "Aldo Moro", Bari, Italy.
authors.forename: Adriano
authors.initials: A
authors.lastname: Fonzino
authors.affiliation: Section of Pharmacology, Dept. of Pharmacy & Drug Sciences, University of Bari "Aldo Moro", Bari, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Conte
authors.affiliation: Galapagos-SASU, Romainville, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Jagerschmidt
authors.affiliation: Galapagos-SASU, Romainville, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Namour
authors.affiliation: Section of Pharmacology, Dept. of Pharmacy & Drug Sciences, University of Bari "Aldo Moro", Bari, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Liantonio
authors.affiliation: Section of Pharmacology, Dept. of Pharmacy & Drug Sciences, University of Bari "Aldo Moro", Bari, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: De Luca
authors.affiliation: Section of Pharmacology, Dept. of Pharmacy & Drug Sciences, University of Bari "Aldo Moro", Bari, Italy.
authors.forename: Diana
authors.initials: D
authors.lastname: Conte Camerino
authors.affiliation: Section of Pharmacology, Dept. of Pharmacy & Drug Sciences, University of Bari "Aldo Moro", Bari, Italy.
authors.forename: Sabata
authors.initials: S
authors.lastname: Pierno
mesh_terms: D045930:Anabolic Agents / Q000494:pharmacology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics; D006614:Hindlimb / Q000187:drug effects / Q000503:physiopathology; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009133:Muscular Atrophy / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D009277:Nandrolone / Q000494:pharmacology*; D014176:Protein Biosynthesis / Q000187:drug effects
chemical_list: D045930:Anabolic Agents; D009277:Nandrolone; D002118:Calcium