Manganese exposure induces α-synuclein aggregation in the frontal cortex of non-human primates

Aggregation of alpha-synuclein (alpha-syn) in the brain is a defining pathological feature of neurodegenerative disorders classified as synucleinopathies. They include Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Occupational and environmental exposure to manganese (Mn) is associated with a neurological syndrome consisting of psychiatric symptoms, cognitive impairment and parkinsonism. In this study, we examined alpha-syn immunoreactivity in the frontal cortex of Cynomolgus macaques as part of a multidisciplinary assessment of the neurological effects produced by exposure to moderate levels of Mn. We found increased alpha-syn-positive cells in the gray matter of Mn-exposed animals, typically observed in pyramidal and medium-sized neurons in deep cortical layers. Some of these neurons displayed loss of Nissl staining with alpha-syn-positive spherical aggregates. In the white matter we also observed alpha-syn-positive glial cells and in some cases alpha-syn-positive neurites. These findings suggest that Mn exposure promotes alpha-syn aggregation in neuronal and glial cells that may ultimately lead to degeneration in the frontal cortex gray and white matter. To our knowledge, this is the first report of Mn-induced neuronal and glial cell alpha-syn accumulation and aggregation in the frontal cortex of non-human primates. (C) 2012 Elsevier Ireland Ltd. All rights reserved.