Manganese Induces Dopaminergic Neurodegeneration via Microglial Activation in a Rat Model of Manganism

Manganese is an essential trace element required for normal development and bodily functions. However, exposure of the brain to excessive amounts of manganese results in neurotoxicity. Although previous studies examining manganese neurotoxicity have focused on neuronal injury, especially direct injury to dopaminergic neurons, the effects of manganese-induced neuro-toxicity on glial cells have not been reported. The current study was designed to examine the effect of manganese on microglial activation, and the underlying mechanism of manganese-induced dopaminergic neuronal injury in vivo. We established an animal model of manganism by intrastriatal injection of MnCl24H2O into male Sprague-Dawley rats. One day after administration of manganese, a few microglial cells in the substantia nigra (SN) were activated, although the number of tyrosine hydroxylase (TH)–immunoreactive neurons in the SN was unaffected. Seve