Developmental Exposure to Manganese Increases Adult Susceptibility to Inflammatory Activation of Glia and Neuronal Protein Nitration

• DOI: 10.1093/toxsci/kfp221
• Publication Date: 2009-10-08T02:13:30Z
• Authors: Julie A. Moreno; Karin M. Streifel; Kelly A. Sullivan; Marie E. Legare; Ronald B. Tjalkens
• Keywords: Gliosis; Astrogliosis; Neurotoxicity; Neuroglia; Astrocytosis

Chronic exposure to manganese (Mn) produces a neurodegenerative disorder affecting the basal ganglia characterized by reactive gliosis and expression of neuroinflammatory genes including inducible nitric oxide synthase (NOS2). Induction NOS2 in glial cells causes overproduction (NO) injury neurons that is associated with parkinsonian-like motor deficits. Inflammatory activation glia believed be an early event Mn neurotoxicity, but specific responses microglia astrocytes during development remain poorly understood. In this study, we investigated effect juvenile on production NO C57Bl/6J mice, postulating developmental would lead heightened sensitivity increased adult mice exposed again later life. Immunohistochemical analysis indicated caused both striatum (St), globus pallidus (Gp), substantia nigra pars reticulata (SNpr) treated compared controls. More robust was observed juveniles, whereas astrogliosis more prominent preexposed development. Co-immunofluorescence studies demonstrated located Gp SNpr. Additionally, greater increases level 3-nitrotyrosine protein adducts were detected dopamine- cAMP-regulated phosphoprotein-32–positive St Mn-treated as juveniles. These data indicate subchronic leads temporally distinct patterns result elevated nitrosative stress populations neurons.