title: Selective vulnerability of spinal and cortical motor neuron subpopulations in delta7 SMA mice.
abstract: Loss of the survival motor neuron gene (SMN1) is responsible for spinal muscular atrophy (SMA), the most common inherited cause of infant mortality. Even though the SMA phenotype is traditionally considered as related to spinal motor neuron loss, it remains debated whether the specific targeting of motor neurons could represent the best therapeutic option for the disease. We here investigated, using stereological quantification methods, the spinal cord and cerebral motor cortex of ∆7 SMA mice during development, to verify extent and selectivity of motor neuron loss. We found progressive post-natal loss of spinal motor neurons, already at pre-symptomatic stages, and a higher vulnerability of motor neurons innervating proximal and axial muscles. Larger motor neurons decreased in the course of disease, either for selective loss or specific developmental impairment. We also found a selective reduction of layer V pyramidal neurons associated with layer V gliosis in the cerebral motor cortex. Our data indicate that in the ∆7 SMA model SMN loss is critical for the spinal cord, particularly for specific motor neuron pools. Neuronal loss, however, is not selective for lower motor neurons. These data further suggest that SMA pathogenesis is likely more complex than previously anticipated. The better knowledge of SMA models might be instrumental in shaping better therapeutic options for affected patients.
authors: Molecular Neuroanatomy and Pathogenesis Unit, IRCCS Neurological Institute "C. Besta", Milano, Italy.
authors: Paolo
authors: P
authors: d'Errico
authors: Marina
authors: M
authors: Boido
authors: Antonio
authors: A
authors: Piras
authors: Valeria
authors: V
authors: Valsecchi
authors: Elena
authors: E
authors: De Amicis
authors: Denise
authors: D
authors: Locatelli
authors: Silvia
authors: S
authors: Capra
authors: Francesco
authors: F
authors: Vagni
authors: Alessandro
authors: A
authors: Vercelli
authors: Giorgio
authors: G
authors: Battaglia
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology*; D059329:Cholinergic Neurons / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005911:Gliosis; D051379:Mice; D018345:Mice, Knockout; D009044:Motor Cortex / Q000378:metabolism / Q000473:pathology; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology*; D009134:Muscular Atrophy, Spinal / Q000235:genetics / Q000473:pathology*; D017966:Pyramidal Cells / Q000378:metabolism / Q000473:pathology; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology*; D055533:Survival of Motor Neuron 1 Protein / Q000235:genetics
chemical_list: D055533:Survival of Motor Neuron 1 Protein