EARLY MOTOR IMPAIRMENTS IN SOD1 MICE ARE RELIABLY DETECTED VIA HOME-CAGE VOLUNTARY WHEEL-RUNNING: EFFECT OF EXERCISE AND COMPARISON WITH ROTAROD

Assessment of motor function is crucial in mouse models of neurodegenerative diseases and it is usually obtained via Rotarod. To complement Rotarod assessments, we recently validated an automated home-cage based running-wheel system (TSE Systems) that enables continuous monitoring of motor performance without handler interference, desirable in longitudinal studies. To study how motor deficits vary with respect to sex, age of onset, rate of progression and severity of symptoms, we investigated wheel running in a genetic model of Amyotrophic Lateral Sclerosis, Tg(SOD1G93A)dl1/GurJ (SOD1) and in parallel we measured performance on Rotarod at different ages. In addition, we challenged male and female mice on one or multiple 3-weeks sessions to verify the effect of voluntary wheel running on the disease progression, motor function and survival. Several parameters of motor behaviour were analysed through Principal Component Analysis in order to detect what indices may be comparable between tests and may be useful for early detection of symptoms. Wheel-running difficulties were observed in SOD1 mutants earlier than using only the Rotarod, making this tool a method capable of detecting deficits at pre-symptomatic stages. Moreover, wheel running activity, Rotarod performance and survival were differentially altered in older male and female SOD1 mice depending on exposure to previous running sessions. Subsequently SOD1 mutants were tested in another automated home-cage apparatus to evaluate cognitive timing ability and its circadian regulation. Error rate at discrete time points across the light-dark cycle was diminished in mutants and their ability to discriminate between short and long intervals differed from WT.