Mitochondrial-dependent manganese neurotoxicity in rat primary astrocyte cultures

Zhaoobao Yin, Judy L. Aschner, Ana Paula dos Santos, Michael Aschner

Research output: Contribution to journalArticle

82 Citations (Scopus)

Abstract

Chronic exposure to excessive levels of Mn results in a movement disorder termed manganism, which resembles Parkinson's disease (PD). The pathogenic mechanisms underlying this disorder are not fully understood. Several lines of evidence implicate astrocytes as an early target of Mn neurotoxicity. In the present study, we investigated the effects of Mn on mitochondrial function. Primary astrocyte cultures were prepared from cerebral cortices of one-day-old Sprague-Dawley rats. We have examined the cellular toxicity of Mn and its effects on the phosphorylation of extracellular signal-regulated kinase (ERK) and activation of the precursor protein of caspase-3. The potentiometric dye, tetramethyl rhodamine ethyl ester (TMRE), was used to assess the effect of Mn on astrocytic mitochondrial inner membrane potential (ΔΨm). Our studies show that, in a concentration-dependent manner, Mn induces significant (p < 0.05) activation of astrocyte caspase-3 and phosphorylated extracellular signal-regulated kinase (p-ERK). Mn treatment (1 and 6 h) also significantly (p < 0.01) dissipates the ΔΨm in astrocytes as evidenced by a decrease in mitochondrial TMRE fluorescence. These results suggest that activations of astrocytic caspase-3 and ERK are involved in Mn-induced neurotoxicity via mitochondrial-dependent pathways.

Original languageEnglish (US)
Pages (from-to)1-11
Number of pages11
JournalBrain Research
Volume1203
DOIs
StatePublished - Apr 8 2008
Externally publishedYes

Fingerprint

Manganese
Astrocytes
Extracellular Signal-Regulated MAP Kinases
Caspase 3
Protein Precursors
Mitochondrial Membrane Potential
Movement Disorders
Cerebral Cortex
Sprague Dawley Rats
Parkinson Disease
Coloring Agents
Fluorescence
Phosphorylation
tetramethyl rhodamine ethyl ester

Keywords

  • Astrocyte
  • ERK signaling pathway
  • Manganese
  • Manganese neurotoxicity
  • Mitochondria
  • Oxidative stress

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

Cite this

Mitochondrial-dependent manganese neurotoxicity in rat primary astrocyte cultures. / Yin, Zhaoobao; Aschner, Judy L.; dos Santos, Ana Paula; Aschner, Michael.

In: Brain Research, Vol. 1203, 08.04.2008, p. 1-11.

Research output: Contribution to journalArticle

@article{ff94c3161ff44075bae25789b62ff5f4,
title = "Mitochondrial-dependent manganese neurotoxicity in rat primary astrocyte cultures",
abstract = "Chronic exposure to excessive levels of Mn results in a movement disorder termed manganism, which resembles Parkinson's disease (PD). The pathogenic mechanisms underlying this disorder are not fully understood. Several lines of evidence implicate astrocytes as an early target of Mn neurotoxicity. In the present study, we investigated the effects of Mn on mitochondrial function. Primary astrocyte cultures were prepared from cerebral cortices of one-day-old Sprague-Dawley rats. We have examined the cellular toxicity of Mn and its effects on the phosphorylation of extracellular signal-regulated kinase (ERK) and activation of the precursor protein of caspase-3. The potentiometric dye, tetramethyl rhodamine ethyl ester (TMRE), was used to assess the effect of Mn on astrocytic mitochondrial inner membrane potential (ΔΨm). Our studies show that, in a concentration-dependent manner, Mn induces significant (p < 0.05) activation of astrocyte caspase-3 and phosphorylated extracellular signal-regulated kinase (p-ERK). Mn treatment (1 and 6 h) also significantly (p < 0.01) dissipates the ΔΨm in astrocytes as evidenced by a decrease in mitochondrial TMRE fluorescence. These results suggest that activations of astrocytic caspase-3 and ERK are involved in Mn-induced neurotoxicity via mitochondrial-dependent pathways.",
keywords = "Astrocyte, ERK signaling pathway, Manganese, Manganese neurotoxicity, Mitochondria, Oxidative stress",
author = "Zhaoobao Yin and Aschner, {Judy L.} and {dos Santos}, {Ana Paula} and Michael Aschner",
year = "2008",
month = "4",
day = "8",
doi = "10.1016/j.brainres.2008.01.079",
language = "English (US)",
volume = "1203",
pages = "1--11",
journal = "Brain Research",
issn = "0006-8993",
publisher = "Elsevier",

}

TY - JOUR

T1 - Mitochondrial-dependent manganese neurotoxicity in rat primary astrocyte cultures

AU - Yin, Zhaoobao

AU - Aschner, Judy L.

AU - dos Santos, Ana Paula

AU - Aschner, Michael

PY - 2008/4/8

Y1 - 2008/4/8

N2 - Chronic exposure to excessive levels of Mn results in a movement disorder termed manganism, which resembles Parkinson's disease (PD). The pathogenic mechanisms underlying this disorder are not fully understood. Several lines of evidence implicate astrocytes as an early target of Mn neurotoxicity. In the present study, we investigated the effects of Mn on mitochondrial function. Primary astrocyte cultures were prepared from cerebral cortices of one-day-old Sprague-Dawley rats. We have examined the cellular toxicity of Mn and its effects on the phosphorylation of extracellular signal-regulated kinase (ERK) and activation of the precursor protein of caspase-3. The potentiometric dye, tetramethyl rhodamine ethyl ester (TMRE), was used to assess the effect of Mn on astrocytic mitochondrial inner membrane potential (ΔΨm). Our studies show that, in a concentration-dependent manner, Mn induces significant (p < 0.05) activation of astrocyte caspase-3 and phosphorylated extracellular signal-regulated kinase (p-ERK). Mn treatment (1 and 6 h) also significantly (p < 0.01) dissipates the ΔΨm in astrocytes as evidenced by a decrease in mitochondrial TMRE fluorescence. These results suggest that activations of astrocytic caspase-3 and ERK are involved in Mn-induced neurotoxicity via mitochondrial-dependent pathways.

AB - Chronic exposure to excessive levels of Mn results in a movement disorder termed manganism, which resembles Parkinson's disease (PD). The pathogenic mechanisms underlying this disorder are not fully understood. Several lines of evidence implicate astrocytes as an early target of Mn neurotoxicity. In the present study, we investigated the effects of Mn on mitochondrial function. Primary astrocyte cultures were prepared from cerebral cortices of one-day-old Sprague-Dawley rats. We have examined the cellular toxicity of Mn and its effects on the phosphorylation of extracellular signal-regulated kinase (ERK) and activation of the precursor protein of caspase-3. The potentiometric dye, tetramethyl rhodamine ethyl ester (TMRE), was used to assess the effect of Mn on astrocytic mitochondrial inner membrane potential (ΔΨm). Our studies show that, in a concentration-dependent manner, Mn induces significant (p < 0.05) activation of astrocyte caspase-3 and phosphorylated extracellular signal-regulated kinase (p-ERK). Mn treatment (1 and 6 h) also significantly (p < 0.01) dissipates the ΔΨm in astrocytes as evidenced by a decrease in mitochondrial TMRE fluorescence. These results suggest that activations of astrocytic caspase-3 and ERK are involved in Mn-induced neurotoxicity via mitochondrial-dependent pathways.

KW - Astrocyte

KW - ERK signaling pathway

KW - Manganese

KW - Manganese neurotoxicity

KW - Mitochondria

KW - Oxidative stress

UR - http://www.scopus.com/inward/record.url?scp=40949096857&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=40949096857&partnerID=8YFLogxK

U2 - 10.1016/j.brainres.2008.01.079

DO - 10.1016/j.brainres.2008.01.079

M3 - Article

VL - 1203

SP - 1

EP - 11

JO - Brain Research

JF - Brain Research

SN - 0006-8993

ER -