Distinct and Overlapping Alterations in Motor and Sensory Neurons in a Mouse Model of Spinal Muscular Atrophy (SMA)

Motor neuron degeneration is the predominant pathological feature of spinal muscular atrophy (SMA). In patients with severe forms of the disease, additional sensory abnormalities have been reported. However, it is not clear whether the loss of sensory neurons is a common feature in severe forms of the disease, how many neurons are lost, and how loss of sensory neurons compares with motor neuron degeneration. We have analysed dorsal root ganglionic sensory neurons in Smn-/-;SMN2 mice, a model of type I SMA. In contrast to lumbar motor neurons, no loss of sensory neurons in the L5 dorsal root ganglia is found at postnatal day 3-5 when these mice are severely paralysed and die from motor defects. Survival of cultured sensory neurons in the presence of NGF and other neurotrophic factors is not reduced in comparison to wildtype controls. However, isolated sensory neurons have shorter neurites and smaller growth cones, and β-actin protein and β-actin mRNA are reduced in sensory neurite terminals. In footpads of Smn-deficient mouse embryos, sensory nerve terminals are smaller, suggesting that Smn deficiency reduces neurite outgrowth during embryogenesis. These data indicate that pathological alterations in severe forms of SMA are not restricted to motor neurons, but the defects in the sensory neurons are milder than in motor neurons. by gest on M ay 3, 2016 ht://hm g.oxfournals.org/ D ow nladed from