Catecholaminergic dysfunction drives postural and locomotor deficits in a mouse model of spinal muscular atrophy.

Development and maintenance of posture is essential behavior for overground mammalian locomotion. Dopamine and noradrenaline strongly influence locomotion, and their dysregulation initiates the development of motor impairments linked to neurodegenerative disease. However, the precise cellular and circuit mechanisms are not well defined.

p53-dependent c-Fos expression is a marker but not executor for motor neuron death in spinal muscular atrophy mouse models.

The activation of the p53 pathway has been associated with neuronal degeneration in different neurological disorders, including spinal muscular atrophy (SMA) where aberrant expression of p53 drives selective death of motor neurons destined to degenerate. Since direct p53 inhibition is an unsound therapeutic approach due carcinogenic effects, we investigated the expression of the cell death-associated p53 downstream targets , and in vulnerable motor neurons of SMA mice. Fluorescence hybridization (FISH) of SMA motor neurons revealed RNA as a promising candidate.

Central synaptopathy is the most conserved feature of motor circuit pathology across spinal muscular atrophy mouse models.

Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by reduced survival motor neuron (SMN) protein. Recently, SMN dysfunction has been linked to individual aspects of motor circuit pathology in a severe SMA mouse model. To determine whether these disease mechanisms are conserved, we directly compared the motor circuit pathology of three SMA mouse models.