Exercício forçado e prévio à lesão melhora parâmetros motores e produção de fatores neurotróficos em modelo experimental da doença de Parkinson

Abstract

Animal models are used to investigate the phenomena underlying the pathogenesis of Parkinson's disease (PD) and the effects of neuroprotective or restorative therapeutic interventions on its onset and progression. We aimed to investigate whether previous treadmill exercise can protect against neuronal death in PD rat model, if it can induce astrocytes´ reaction. We also aimed to verify if previous treadmill exercise can improve the early motor symptoms of Parkinson disease and if these benefits are due to Glial cell-line Derived Neurotrophic Factor (GDNF) and Brain Derived Neurotrophic Factor (BDNF) early after injury. Male Wistar rats were submitted to daily moderate-intensity exercise on a motorized treadmill for three weeks before the injection of 6-hydroxydopamine (6-OHDA) in right substantia nigra pars compacta. We evaluated dopaminergic neuron survival, density of astrocytes in ventral midbrain, gait pattern, balance and spontaneous locomotion. In addition, GDNF and BDNF levels in ventral midbrain and striatum were quantified by ELISA at two moments: one hour and three days after injury, in young and also in adult rats. Preinjury moderate-intensity exercise prevented dynamic postural gait impairment and reduced the difficulty in coordinated movements against gravity. It also induced early expression of striatal GDNF and BDNF, but did not prevent dopaminergic neuron death. In conclusion, we suggested that preinjury physical exercise, adjusted to individual performance, is a potentially useful strategy to improve brain response and motor behavior, probably through GDNF and BDNF expression in 6-OHDA rat model of Parkinson disease.