Manganese mixture inhalation is a reliable Parkinson disease model in rats

► Manganese inhalation as a Parkinson disease model is progressive and bilateral which makes it more reliable. ► This model has only been characterized in mice. ► In order to have a well-supported and generalizable model in rodents, we used rats that inhaled a mixture of Manganese compounds. ► The mixture of Manganese compounds in rats caused motor alterations and 75.95% loss of dopaminergic neurons. ► The inhalation of the mixture of Mn compounds is a useful model in rodents for the study of PD. Manganese (Mn) is an essential trace metal. Regardless of its essentiality, it has been reported that the overexposure causes neurotoxicity manifested as extrapyramidal symptoms similar to those observed in Parkinson disease (PD). Recently, our group reported that mice that inhaled for 5 months the mixture of manganese chloride (MnCl2) and manganese acetate Mn(OAc)3 developed movement abnormalities, significant loss of substantia nigra compacta (SNc) dopaminergic neurons, dopamine depletion and improved behavior with l-DOPA treatment. However, this model has only been characterized in mice. In order to have a well-supported and generalizable model in rodents, we used male Wistar rats that inhaled a mixture of 0.04M MnCl2 and 0.02M Mn(OAc)3, 1h three times a week for 6 months. Before Mn exposure, animals were trained to perform motor tests (Beam-walking and Single-pellet reaching tasks) and were evaluated each week after the exposure. The mixture of MnCl2/Mn(OAc)3 caused alterations in the motor tests, 75.95% loss of SNc dopaminergic neurons, and no cell alterations in Globus Pallidus or striatum. With these results we conclude that the inhalation of the mixture of Mn compounds is a useful model in rodents for the study of PD.