Inhalation of divalent and trivalent manganese mixture induces a Parkinson's disease model: Immunocytochemical and behavioral evidences

The present study investigates the effects of divalent and trivalent manganese (Mn2+/Mn3+) mixture inhalation on mice to obtain a novel animal model of Parkinson disease (PD) inducing bilateral and progressive cell death in the substantia nigra compacta (SNc) and correlating these alterations with motor disturbances. CD-1 male mice inhaled a mixture of 0.04 M manganese chloride (MnCl2) and manganese acetate (Mn(OAc)3), 1 h twice a week for 5 months. Before Mn exposure, animals were trained to perform motor function tests and were evaluated each week after the exposure. By doing this, overall behavior was assessed by ratings and by videotaped analyses; by the end of Mn exposure period, animals were killed. The mesencephalon was processed for tyrosine hydroxylase (TH) immunocytochemistry. After 5 months of Mn mixture inhalation, mice developed evident deficits in their motor performance manifested as akinesia, postural instability and action tremor. SNc of the Mn-exposed animals showed an important decrease (67.58%) in the number of TH-immunopositive neurons. Our data provide evidence that MnCl2 and Mn(OAc)3 mixture inhalation produces similar morphological and behavioral alterations to those observed in PD providing a useful experimental model for the study of this neurodegenerative disease.