Manganese exposure induces microglia activation and dystrophy in the substantia nigra of non-human primates

Neurotoxicology. 2011 Mar;32(2):215-26. doi: 10.1016/j.neuro.2010.11.003. Epub 2010 Nov 26.

Abstract

Chronic manganese (Mn) exposure produces neurological deficits including a form of parkinsonism that is different from Parkinson's disease (PD). In chronic Mn exposure, dopamine neurons in the substantia nigra (SN) do not degenerate but they appear to be dysfunctional. Further, previous studies have suggested that the substantia nigra pars reticulata (SNr) is affected by Mn. In the present study, we investigated whether chronic Mn exposure induces microglia activation in the substantia nigra pars compacta (SNc) and SNr in Cynomolgus macaques. Animals were exposed to different weekly doses of Mn (3.3-5.0, 5.0-6.7, 8.3-10 mg Mn/kg body weight) and microglia were examined in the substantia nigra using LN3 immunohistochemistry. We observed that in control animals, LN3 labeled microglia were characterized by a resting phenotype. However, in Mn-treated animals, microglia increased in number and displayed reactive changes with increasing Mn exposure. This effect was more prominent in the SNr than in the SNc. In the SNr of animals administered the highest Mn dose, microglia activation was the most advanced and included dystrophic changes. Reactive microglia expressed increased iNOS, L-ferritin, and intracellular ferric iron which were particularly prominent in dystrophic compartments. Our observations indicate that moderate Mn exposure produces structural changes on microglia, which may have significant consequences on their function.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Macaca
  • Macaca fascicularis
  • Male
  • Manganese / administration & dosage*
  • Manganese / toxicity*
  • Microglia / drug effects*
  • Microglia / metabolism
  • Microglia / pathology
  • Muscular Dystrophies / chemically induced*
  • Muscular Dystrophies / metabolism
  • Muscular Dystrophies / pathology
  • Nerve Degeneration / chemically induced
  • Nerve Degeneration / metabolism
  • Substantia Nigra / drug effects*
  • Substantia Nigra / metabolism
  • Substantia Nigra / pathology

Substances

  • Manganese