TY - JOUR
T1 - Riluzole, unlike the AMPA antagonist RPR119990, reduces motor impairment and partially prevents motoneuron death in the wobbler mouse, a model of neurodegenerative disease
AU - Fumagalli, Elena
AU - Bigini, Paolo
AU - Barbera, Sara
AU - De Paola, Massimiliano
AU - Mennini, Tiziana
PY - 2006/3
Y1 - 2006/3
N2 - The wobbler mouse is one of the most useful models of motoneuron degeneration, characterized by selective motoneuronal death in the cervical spinal cord. We carried out two parallel studies in wobbler mice, comparing the anti-glutamatergic drug riluzole and the AMPA receptor antagonist RPR119990. Mice were treated with 40 mg/kg/day of riluzole or with 3 mg/kg/day of RPR119990 from the 4th to the 12th week of age. Here, we show that chronic treatment with riluzole improves motor behavior, prevents biceps muscle atrophy and decreases the amount of motoneuron loss in treated wobbler mice. Chronic treatment with the AMPA antagonist RPR119990 is ineffective in improving motor impairment, in reducing motoneuronal loss and muscular atrophy in treated mice. These results, together with the unchanged immunostaining for the AMPA receptor subunit GluR2 in wobbler mice, suggest that AMPA receptor-mediated injury is unlikely to be involved in neurodegeneration in wobbler disease, and that the protective effect of riluzole in wobbler mice seems to be independent of its anti-glutamatergic activity, as suggested in other models of neurodegeneration. Immunostaining of cervical spinal cord sections shows that in riluzole-treated wobbler mice BDNF expression is significantly increased in motoneurons with no changes in the high-affinity receptor Trk-B. Our data confirm that riluzole has beneficial effects in wobbler mice, and suggest that these effects could be associated to the increased levels of the neurotrophic and neuroprotective factor BDNF.
AB - The wobbler mouse is one of the most useful models of motoneuron degeneration, characterized by selective motoneuronal death in the cervical spinal cord. We carried out two parallel studies in wobbler mice, comparing the anti-glutamatergic drug riluzole and the AMPA receptor antagonist RPR119990. Mice were treated with 40 mg/kg/day of riluzole or with 3 mg/kg/day of RPR119990 from the 4th to the 12th week of age. Here, we show that chronic treatment with riluzole improves motor behavior, prevents biceps muscle atrophy and decreases the amount of motoneuron loss in treated wobbler mice. Chronic treatment with the AMPA antagonist RPR119990 is ineffective in improving motor impairment, in reducing motoneuronal loss and muscular atrophy in treated mice. These results, together with the unchanged immunostaining for the AMPA receptor subunit GluR2 in wobbler mice, suggest that AMPA receptor-mediated injury is unlikely to be involved in neurodegeneration in wobbler disease, and that the protective effect of riluzole in wobbler mice seems to be independent of its anti-glutamatergic activity, as suggested in other models of neurodegeneration. Immunostaining of cervical spinal cord sections shows that in riluzole-treated wobbler mice BDNF expression is significantly increased in motoneurons with no changes in the high-affinity receptor Trk-B. Our data confirm that riluzole has beneficial effects in wobbler mice, and suggest that these effects could be associated to the increased levels of the neurotrophic and neuroprotective factor BDNF.
KW - AMPA receptors
KW - Amyotrophic lateral sclerosis
KW - BDNF
KW - Glutamate excitotoxicity
KW - Motoneuron
KW - Neurodegeneration
KW - Neuroprotection
KW - Riluzole
KW - RPR119990
KW - Wobbler
UR - http://www.scopus.com/inward/record.url?scp=32644434547&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=32644434547&partnerID=8YFLogxK
U2 - 10.1016/j.expneurol.2005.11.010
DO - 10.1016/j.expneurol.2005.11.010
M3 - Article
C2 - 16386734
AN - SCOPUS:32644434547
VL - 198
SP - 114
EP - 128
JO - Experimental Neurology
JF - Experimental Neurology
SN - 0014-4886
IS - 1
ER -