Sensorimotor and cognitive functions in a SOD1G37R transgenic mouse model of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurological disorder involving degeneration of motor neurons in brain and spinal cord, leading to progressive atrophy of skeletal muscles and, ultimately, paralysis and death. Copper-mediated oxidative damage is proposed to play a critical role in the pathogenesis of Cu/Zn superoxide dismutase (SOD1) – linked hereditary amyotrophic lateral sclerosis. To understand more clearly the pathogenesis of sensorimotor dysfunction and to find the most appropriate methods for early detection of symptoms and for monitoring them across time, a murine model was assessed at three time points (5, 8, and 11 months). Transgenic mice with the G37R mutation of human SOD1 exhibited earliest signs of dysfunction at 8 months in terms of a pathological hindpaw clasping reflex, as well as slowed movement time on a suspended bar, anomalies in footprint patterns, weaker grip strength, raised somatosensory thresholds, and deficits in passive avoidance learning, yielding a margin of 3–4 months before death to test experimental therapies.

► SODG37R transgenic mice were used to find the most appropriate diagnostic methods.
► This model recapitulate some aspects of human ALS pathology.
► The transgenics exhibited earliest deficits in sensorimotor and cognitive skills.
► The present analyses provides an opportunity for early detection of symptom onset.
► This approach permit testing experimental therapies aimed to improving ALS symptoms.