Alzheimer type II astrocytic changes following sub-acute exposure to manganese and its prevention by antioxidant treatment

Alan S. Hazell, Louise Normandin, Michael D Norenberg, Gregory Kennedy, Jae Hyuk Yi

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Exposure to manganese in an industrial or clinical setting can lead to manganism, a neurological disorder with similarities to Parkinson's disease. Although the pathogenetic basis of this disorder is unclear, studies indicate this metal is highly accumulated in astrocytes, suggesting an involvement of these glial cells. To investigate this issue, we have used a recently characterized, sub-acute model of manganese neurotoxicity. Treatment of rats with manganese (II) chloride (50 mg/kg body weight, i.p.) once daily for 1 or 4 days led to increases in manganese levels of up to 232, 523, and 427% in the cerebral cortex, globus pallidus, and cerebellum, respectively, by instrumental neutron activation analysis. These changes were accompanied by development of pathological changes in glial morphology identified as Alzheimer type II astrocytosis in both cortical and sub-cortical structures. Co-treatment with either the antioxidant N-acetylcysteine or the manganese chelator 1,2-cyclohexylenedinitrilotetraacetic acid completely blocked this pathology, indicating the cellular transformation may be mediated by oxidative stress associated with the presence of this metal. These findings represent, to our knowledge, the first report of early induction of this pathological hallmark of manganese neurotoxicity, an event previously considered a consequence of chronic exposure to manganese in primates and in human cases of manganism. Our results also indicate that use of this rodent model may provide a novel opportunity to examine the nature and role of the Alzheimer type II astrocyte in the pathophysiology of this disorder as well as in other disease processes in which cerebral accumulation of manganese occurs.

Original languageEnglish
Pages (from-to)167-171
Number of pages5
JournalNeuroscience Letters
Volume396
Issue number3
DOIs
StatePublished - Apr 3 2006

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Manganese
Antioxidants
Neuroglia
Astrocytes
Metals
Neutron Activation Analysis
Globus Pallidus
Gliosis
Acetylcysteine
Chelating Agents
Nervous System Diseases
Cerebral Cortex
Cerebellum
Primates
Parkinson Disease
Rodentia
Oxidative Stress
Body Weight
Pathology
Acids

Keywords

  • Alzheimer type II astrocytosis
  • Astrocyte
  • Globus pallidus
  • Manganese neurotoxicity
  • Manganism
  • Oxidative stress

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Alzheimer type II astrocytic changes following sub-acute exposure to manganese and its prevention by antioxidant treatment. / Hazell, Alan S.; Normandin, Louise; Norenberg, Michael D; Kennedy, Gregory; Yi, Jae Hyuk.

In: Neuroscience Letters, Vol. 396, No. 3, 03.04.2006, p. 167-171.

Research output: Contribution to journalArticle

Hazell, Alan S. ; Normandin, Louise ; Norenberg, Michael D ; Kennedy, Gregory ; Yi, Jae Hyuk. / Alzheimer type II astrocytic changes following sub-acute exposure to manganese and its prevention by antioxidant treatment. In: Neuroscience Letters. 2006 ; Vol. 396, No. 3. pp. 167-171.
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