REDUCED BRANCHING AND LENGTH OF DENDRITES DETECTED IN CERVICAL SPINAL-CORD MOTONEURONS OF WOBBLER MOUSE, A MODEL FOR INHERITED MOTONEURON DISEASE

The Wobbler mouse (wr) has been proposed as a model for human inherited motoneuron disease (infantile spinal muscular atrophy). The primary defect is thought to be in the motoneurons. Therefore we undertook a survey of the qualitative and quantitative changes occurring in the cervical spinal motoneurons of Wobbler mice during a late stage of the motoneuron disease compared with age- and sex-matched normal phenotype (NFR/wr) littermates. The Rapid Golgi Method was applied. In control and Wobbler mice, four types of neurons were identified according to their dendritic patterns: multipolar, tripolar, bipolar, and unipolar cells. Unipolar cells were observed more often in the Wobbler specimens than the controls and may represent a final stage in the degeneration of other cell types with greater numbers of primary dendrites. Medium (300-999-mu-m2) and large (> 1,000-mu-m2) impregnated neurons (presumably alpha-motoneurons) showed strong indications of cell degeneration, including statistically significant reductions in the measurements for dendritic length, distribution, and branching, as well as the number of spines. In contrast, the small (< 300-mu-m2) neurons showed only mild signs of degeneration, including slight reductions in dendritic length, but no significant differences appeared in the distribution and branching of dendrites, or in the number of spines. Instead, a small increase could be detected in the number of primary and secondary dendritic branches emanating from the small neurons, as well as in the number of dendritic spines. These findings suggest that sprouting may occur to a slight extent. Although previous studies document that swelling with subsequent vacuolation of motoneurons is the predominant feature characterizing the Wobbler disease, the mean soma area (mu-m2) calculated for the impregnated neurons of the Wobbler specimens showed no significant difference from the controls. It is hypothesized that the advanced signs of the Wobbler motoneuron disease are primarily reflected in the degeneration of the dendrites and spines on the medium and large alpha-motoneurons. The small neurons (presumably a mixed population of gamma-motoneurons, interneurons, and Renshaw cells) possess dendrites and spines that seem to be less affected, and instead show signs of sprouting.