Altered reaction of facial motoneurons to axonal damage in the presymptomatic phase of a murine model of familial amyotrophic lateral sclerosis.
In transgenic mice carrying the G93A human mutation of Cu/Zn superoxide dismutase (SOD1), which provide a model of familial amyotrophic lateral sclerosis, we investigated, before the onset of symptoms, two parameters of the response of facial motoneurons to nerve transection, i.e. nitric oxide synthase induction and motoneuron loss. Axotomy elicited after 2 and 3 weeks high nitric oxide synthase expression in facial motoneurons of wild-type mice, whereas the induction was very weak or absent in transgenic mice. At 1 month post-axotomy, loss of facial motoneurons was significantly higher in mutant mice than in wild-type littermates. Thus, SOD1 mutation interferes with the oxidative cascade elicited by axonal injury in cranial motoneurons. The results also indicate that the adverse gain of function of the mutant SOD1 enhances the vulnerability of motoneurons to peripheral stressful conditions.
Mariotti
R
R
Department of Morphological and Biomedical Sciences, University of Verona, Faculty of Medicine, Strada Le Grazie 8, Italy.
Cristino
L
L
Bressan
C
C
Boscolo
S
S
Bentivoglio
M
M
D000690:Amyotrophic Lateral Sclerosis / Q000473:pathology*; D000818:Animals; D019771:Axotomy; D002452:Cell Count; D004195:Disease Models, Animal; D005154:Facial Nerve / Q000473:pathology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000201:enzymology / Q000473:pathology*; D009252:NADPH Dehydrogenase / Q000032:analysis; D019001:Nitric Oxide Synthase / Q000032:analysis; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1
C000606290:SOD1 protein, human; D019001:Nitric Oxide Synthase; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D009252:NADPH Dehydrogenase