Retrograde transport rates in the G93A mouse model of amyotrophic lateral sclerosis

Amyotrophic Lateral Sclerosis is a late-onset, progressive neuromuscular disease involving degeneration of corticospinal tracts and motor neurons in the brain stem and spinal cord. Recently, it has been suggested that ALS results from a "dying back" axonopathy as opposed to originating in the motor neuron cell body. This is supported by a reduction of neuromuscular junctions in skeletal muscle prior to symptom onset and motor neuron death. It is known that there is a slowing of retrograde transport when comparing presymptomatic and end-stage mice; however, when during disease progression this occurs has not been clarified. By using a retrograde tracer, I sought to observe retrograde transport rates during disease progression in the G93A mouse, a murine model of ALS. Results indicate that retrograde transport is attenuated before symptom onset, loss of motor neurons, and precedes alterations in anterograde transport indicating this is one of the earliest pathological events in ALS.