Effects of Aging in the Striatum and Substantia Nigra of a Parkinson's Disease Animal Model

Aging is a multifactorial process associated with functional deficits, and the brain is more prone to developing chronic degenerative diseases such as Parkinson's disease. Several groups have tried to correlate the age-related ultrastructural alterations to the neurodegeneration process using in vivo pharmacological models, but due to the limitations of the animal models, particularly in aged animals, the results are difficult to interpret. In this work, we investigated neurodegeneration induced by rotenone, as a pharmacological model of Parkinson's disease, in both young and aged Wistar rats. We assessed animal mobility, tyrosine hydroxylase staining in the substantia nigra pars compacta (SNpc), and TdT-mediated dUTP-biotin nick end labeling-positive nuclei and reactive oxygen species production in the striatum. Interestingly, the mobility impairment, dopaminergic neuron loss, and elevated number of apoptotic nuclei in the striatum of aged control rats were similar to young rotenone-treated animals. Moreover, we observed many ultrastructural alterations, such as swollen mitochondria in the striatum, and massive lipofuscin deposits in the SNpc of the aged rotenone-treated animals. We conclude that the rotenone model can be employed to explore age-related alterations in the ontogeny that can increase vulnerability in the striatum and SNpc, which may contribute to Parkinson's disease pathogenesis.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [FAPESP]Conselho Nacional de Desenvolvimento Cientifico e Tecnologico [CNPq]Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)Univ Fed Sao Paulo, Dept Biol Sci, 275 Arthur Ridel St, BR-09972270 Diadema, SP, BrazilUniv Fed Sao Paulo, Dept Pharmacol, Sao Paulo, BrazilUniv Fed Sao Paulo, Ctr Electron Microscopy, Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Biol Sci, 275 Arthur Ridel St, BR-09972270 Diadema, SP, BrazilUniv Fed Sao Paulo, Dept Pharmacol, Sao Paulo, BrazilUniv Fed Sao Paulo, Ctr Electron Microscopy, Sao Paulo, BrazilFAPESP: 2012/08273-3FAPESP: 2013/20073-2Web of Scienc