title: Effect of physical exercise and anabolic steroid treatment on spinal motoneurons and surrounding glia of wild-type and ALS mice.
abstract: Motoneuron degeneration is the hallmark of amyotrophic lateral sclerosis (ALS). The cause and predisposing factors for sporadic ALS are still unknown. Exposure to a specific environmental risk factors in subjects with a susceptibility genotype may increase the risk of the disease. The role of physical activity and the use of anabolic steroids are still debated in epidemiological studies on patients and murine models of ALS. To assess at the cellular level the role (beneficial or detrimental) of physical exercise and the use of anabolic steroid, we here investigated, in SOD1(G93A) (mSOD1) mice and wild-type littermates, changes in the ventral horn after regular exercise, treatment with the anabolic androgenic steroid 19-nortestosterone (nandrolone), and their combination, compared with matched control sedentary mice. The experiments were pursued for several weeks until symptom onset in mSOD1 mice. Lumbar motoneurons, astrocytes and microglia were analyzed. In wild-type mice, cytological alterations of motoneurons were observed especially after nandrolone treatment. The following main findings were observed in treated mSOD1 mice versus untreated ones: i) nandrolone treatment markedly enhanced motoneuron loss; this detrimental effect was reverted by the combination with exercise, resulting in increased motoneuron survival; ii) astrocytic activation was most marked after nandrolone treatment when motoneuron damage was most severe; iii) microglia activation was most marked after physical exercise when motoneuron damage was less severe. The results indicate a vulnerability of mSOD1 motoneurons to nandrolone treatment, a potential neuroprotective effect of physical exercise, and a modulation by glial cells in the ALS murine model in the examined paradigms.
authors.affiliation: Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.
authors.forename: Roman M
authors.initials: RM
authors.lastname: Kassa
authors.affiliation: Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Bonafede
authors.affiliation: Department of Computer Sciences, University of Verona, Verona, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Boschi
authors.affiliation: Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Bentivoglio
authors.affiliation: Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy. Electronic address: raffaella.mariotti@univr.it.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Mariotti
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D045930:Anabolic Agents / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D000870:Anterior Horn Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D001835:Body Weight; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004195:Disease Models, Animal; D005081:Exercise Therapy; D008159:Lumbar Vertebrae; D008297:Male; D008822:Mice, Transgenic; D009277:Nandrolone / Q000494:pharmacology* / Q000633:toxicity; D009457:Neuroglia / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D011897:Random Allocation; D012420:Running / Q000502:physiology; D057185:Sedentary Behavior
chemical_list: D045930:Anabolic Agents; D009277:Nandrolone; D002795:Choline O-Acetyltransferase
keywords: Amyotrophic lateral sclerosis; Astrocytes; Exercise; Microglia; Mutant SOD1 mice; Nandrolone