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Oxidative Stress Involves in Astrocytic Alterations Induced by Manganese

https://doi.org/10.1006/exnr.2002.7894Get rights and content

Abstract

It is hypothesized that manganese neurotoxicity could be secondary to a diminuition of cellular protective and scavenger mechanisms. Since manganese is known to be sequestered in glial cells, we investigated possible neurotoxic mechanisms involving astrocytes in vitro. Astrocytes differentiated into process-bearing stellate cells in response to manganese treatment. Manganese concentration dependently decreased cellular DNA synthesis, glial fibrillary acidic protein expression, energy production, antioxidant capacity, and glutamate transporter activity. In contrast, manganese increased glutamine synthetase protein expression and cytokine-stimulated interleukin 6 mRNA expression. Under the concentration of 0.1 mM, manganese chloride caused no significant astrocyte death even up to 48 h after treatment. That is, these astrocytic alterations proceeded before the onset of cell demise. As a possible mediator of manganese-derived alterations, we determined intracellular redox state in astrocytes. Manganese time-dependently changed intracellular redox potential into oxidized state. The influx of manganese and its resultant oxidative stress was essential to most of the alterations, except for the action on stellation. Astrocytes are central component of the brain's antioxidant defense. Therefore, the observations suggest that dysfunction of astrocytes possibly involved in neurotoxic action of manganese.

References (51)

  • C.H. Langeveld et al.

    Cultured rat striatal and cortical astrocytes protect mesencephalic dopaminergic neurons against hydrogen peroxide toxicity independent of their effect on neuronal development

    Neurosci. Lett.

    (1995)
  • S.L. Liao et al.

    Differential effects of cytokines and redox potential on glutamate uptake in rat cortical glial cultures

    Neurosci. Lett.

    (2001)
  • S.A. Lipton et al.

    Nitric oxide in the central nervous system

    Prog. Brain Res.

    (1994)
  • S. Miyata et al.

    Morphological plasticity and rearrangement of cytoskeletons in pituicytes cultured from adult rat neurohypophysis

    Neurosci. Res.

    (1999)
  • S. Nagatomo et al.

    Manganese intoxication during total parenteral nutriention: Report of two cases and review of the literature

    J. Neurol. Sci.

    (1999)
  • A. Schousboe

    Transport and metabolism of glutamate and GABA in neurons and glial cells

    Int. Rev. Neurobiol.

    (1981)
  • R.D. Snyder et al.

    Enhancement of cytotoxicity and clastogenicity of L-DOPA and dopamine by manganese and copper

    Mutation Res.

    (1998)
  • M. Spranger et al.

    Manganese augments nitric oxide synthesis in murine astrocytes: A new pathogenetic mechanism in manganism?

    Exp. Neurol.

    (1998)
  • L.M. Ambani et al.

    Brain peroxidase and catalase in Parkinson's disease

    Arch. Neurol.

    (1975)
  • M. Aschner et al.

    Manganese uptake and efflux in cultured rat astrocytes

    J. Neurochem.

    (1992)
  • M. Aschner et al.

    Manganese uptake and distribution in the central nervous system (CNS)

    Neurotoxicol.

    (1999)
  • G. Carl et al.

    Manganese and epilepsy: Brain glutamine synthetase and liver arginase activities in genetically epilspsy prone and chronically seizured rats

    Epilepsia

    (1991)
  • C.J. Chen et al.

    Effects of naloxone on lactate, pyruvate metabolism and antioxidant enzyme activity in rat cerebral ischemia/reperfusion

    Neurosci. Lett.

    (2000)
  • C.J. Chen et al.

    Gliotoxic action of glutamate on cultured astrocytes

    J. Neurochem.

    (2000)
  • C.J. Chen et al.

    Cerebral ischemia/reperfusion injury in rat brain: Effects of naloxone

    NeuroReport

    (2001)
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