Phase validation of neurotoxic animal models of Parkinson's disease

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2012
Telkes, İlknur
Parkinson’s disease (PD) is characterized by the progressive loss of dopaminergic nigral neurons and striatal dopamine resulting in serious motor deficits but also some non-motor anomalies. Animal models of human neurodegenerative diseases are essential for better understanding their pathogenesis and developing efficient therapeutic tools. There are many different PD models, however, none of them is fully reproducing all the symptoms of the disease. In addition, different investigators use different behavioral measures which makes even more difficult to compare and evaluate the results. The aim of the present study was to compare motor and cognitive deficits in two most common models of PD: the Rotenone and 6-OHDA model, using a large battery of neurological tests and a probabilistic learning task. To the best of our knowledge, this is the first study to examine the effects of bilaterally induced Rotenone and 6-OHDA through behavioral test batteries assessing the cardinal motor symptoms and the cognitive abnormality of Parkinson’s Disease in the same rat population. Also, the present study is unique on the basis of providing both longitudinal observations of behaviour in the same treatment group and the cross-sectional comparisons of the behavioural responses between different groups. In the current study, the neurotoxins were applied at relatively low doses of 3-4 μg, bilaterally to the substantia nigra pars compacta (SNpc). Experiments were conducted on 50 young-adult male Sprague–Dawley rats randomly assigned to five experimental groups: Rotenone, 6-OHDA, vehicle (DMSO/Saline), and the intact control. The neurological tests included locomotor activity,catalepsy, rearing, stepping, and rotarod/accelerod tests. They were applied prior to, and on days 4-7-10-20-40-150 while the learning task was applied 49 days after drug infusion.During the first 2 postoperational months, both neurotoxins produced progressive deterioration in motor performance but showing no effect on cognitive functions. Five months after the surgery, regression of bradykinesia but persistence of sensorimotor deficits was noted. The tests’ results suggest different susceptibility of different motor functions to the degeneration of nigro-striatal (N-S) pathway. So, different tests were demonstrated to have different power in detecting similar motor deficits.