Evaluation of the importance of astrocytes when screening for acute toxicity in neuronal cell systems

Elizabeth Woehrling, Eric J. Hill, Mike Coleman

Research output: Contribution to journalArticle

Abstract

Reliable, high throughput, in vitro preliminary screening batteries have the potential to greatly accelerate the rate at which regulatory neurotoxicity data is generated. This study evaluated the importance of astrocytes when predicting acute toxic potential using a neuronal screening battery of pure neuronal (NT2.N) and astrocytic (NT2.A) and integrated neuronal/astrocytic (NT2.N/A) cell systems derived from the human NT2.D1 cell line, using biochemical endpoints (mitochondrial membrane potential (MMP) depolarisation and ATP and GSH depletion). Following exposure for 72 h, the known acute human neurotoxicants trimethyltin-chloride, chloroquine and 6-hydroxydopamine were frequently capable of disrupting biochemical processes in all of the cell systems at non-cytotoxic concentrations. Astrocytes provide key metabolic and protective support to neurons during toxic challenge in vivo and generally the astrocyte containing cell systems showed increased tolerance to toxicant insult compared with the NT2.N mono-culture in vitro. Whilst there was no consistent relationship between MMP, ATP and GSH log IC(50) values for the NT2.N/A and NT2.A cell systems, these data did provide preliminary evidence of modulation of the acute neuronal toxic response by astrocytes. In conclusion, the suitability of NT2 neurons and astrocytes as cell systems for acute toxicity screening deserves further investigation.
LanguageEnglish
Pages103-113
Number of pages11
JournalNeurotoxicity Research
Volume17
Issue number2
Early online date11 Jul 2009
DOIs
Publication statusPublished - Feb 2010

Fingerprint

Astrocytes
Toxicity
Screening
Poisons
Mitochondrial Membrane Potential
Neurons
Biochemical Phenomena
Adenosine Triphosphate
Membranes
Oxidopamine
Depolarization
Chloroquine
Information Systems
Cells
Throughput
Modulation
Cell Line
In Vitro Techniques

Keywords

  • adenosine triphosphate
  • analysis of variance
  • astrocytes
  • cell differentiation
  • transformed cell line
  • tumor cell line
  • coculture techniques
  • preclinical drug evaluation
  • glial fibrillary acidic protein
  • glutathione
  • humans
  • indicators and reagents
  • inhibitory concentration 50
  • mitochondrial membrane potential
  • neurons
  • neurotoxins
  • oxazines
  • spectrophotometry
  • teratocarcinoma
  • tubulin
  • xanthenes

Cite this

@article{9380c38e1b20443291dbee9e07dff355,
title = "Evaluation of the importance of astrocytes when screening for acute toxicity in neuronal cell systems",
abstract = "Reliable, high throughput, in vitro preliminary screening batteries have the potential to greatly accelerate the rate at which regulatory neurotoxicity data is generated. This study evaluated the importance of astrocytes when predicting acute toxic potential using a neuronal screening battery of pure neuronal (NT2.N) and astrocytic (NT2.A) and integrated neuronal/astrocytic (NT2.N/A) cell systems derived from the human NT2.D1 cell line, using biochemical endpoints (mitochondrial membrane potential (MMP) depolarisation and ATP and GSH depletion). Following exposure for 72 h, the known acute human neurotoxicants trimethyltin-chloride, chloroquine and 6-hydroxydopamine were frequently capable of disrupting biochemical processes in all of the cell systems at non-cytotoxic concentrations. Astrocytes provide key metabolic and protective support to neurons during toxic challenge in vivo and generally the astrocyte containing cell systems showed increased tolerance to toxicant insult compared with the NT2.N mono-culture in vitro. Whilst there was no consistent relationship between MMP, ATP and GSH log IC(50) values for the NT2.N/A and NT2.A cell systems, these data did provide preliminary evidence of modulation of the acute neuronal toxic response by astrocytes. In conclusion, the suitability of NT2 neurons and astrocytes as cell systems for acute toxicity screening deserves further investigation.",
keywords = "adenosine triphosphate, analysis of variance, astrocytes, cell differentiation, transformed cell line, tumor cell line, coculture techniques, preclinical drug evaluation, glial fibrillary acidic protein, glutathione, humans, indicators and reagents, inhibitory concentration 50, mitochondrial membrane potential, neurons, neurotoxins, oxazines, spectrophotometry, teratocarcinoma, tubulin, xanthenes",
author = "Elizabeth Woehrling and {J. Hill}, Eric and Mike Coleman",
year = "2010",
month = "2",
doi = "10.1007/s12640-009-9084-3",
language = "English",
volume = "17",
pages = "103--113",
journal = "Neurotoxicity Research",
issn = "1029-8428",
publisher = "Springer",
number = "2",

}

Evaluation of the importance of astrocytes when screening for acute toxicity in neuronal cell systems. / Woehrling, Elizabeth; J. Hill, Eric; Coleman, Mike.

In: Neurotoxicity Research, Vol. 17, No. 2, 02.2010, p. 103-113.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Evaluation of the importance of astrocytes when screening for acute toxicity in neuronal cell systems

AU - Woehrling, Elizabeth

AU - J. Hill, Eric

AU - Coleman, Mike

PY - 2010/2

Y1 - 2010/2

N2 - Reliable, high throughput, in vitro preliminary screening batteries have the potential to greatly accelerate the rate at which regulatory neurotoxicity data is generated. This study evaluated the importance of astrocytes when predicting acute toxic potential using a neuronal screening battery of pure neuronal (NT2.N) and astrocytic (NT2.A) and integrated neuronal/astrocytic (NT2.N/A) cell systems derived from the human NT2.D1 cell line, using biochemical endpoints (mitochondrial membrane potential (MMP) depolarisation and ATP and GSH depletion). Following exposure for 72 h, the known acute human neurotoxicants trimethyltin-chloride, chloroquine and 6-hydroxydopamine were frequently capable of disrupting biochemical processes in all of the cell systems at non-cytotoxic concentrations. Astrocytes provide key metabolic and protective support to neurons during toxic challenge in vivo and generally the astrocyte containing cell systems showed increased tolerance to toxicant insult compared with the NT2.N mono-culture in vitro. Whilst there was no consistent relationship between MMP, ATP and GSH log IC(50) values for the NT2.N/A and NT2.A cell systems, these data did provide preliminary evidence of modulation of the acute neuronal toxic response by astrocytes. In conclusion, the suitability of NT2 neurons and astrocytes as cell systems for acute toxicity screening deserves further investigation.

AB - Reliable, high throughput, in vitro preliminary screening batteries have the potential to greatly accelerate the rate at which regulatory neurotoxicity data is generated. This study evaluated the importance of astrocytes when predicting acute toxic potential using a neuronal screening battery of pure neuronal (NT2.N) and astrocytic (NT2.A) and integrated neuronal/astrocytic (NT2.N/A) cell systems derived from the human NT2.D1 cell line, using biochemical endpoints (mitochondrial membrane potential (MMP) depolarisation and ATP and GSH depletion). Following exposure for 72 h, the known acute human neurotoxicants trimethyltin-chloride, chloroquine and 6-hydroxydopamine were frequently capable of disrupting biochemical processes in all of the cell systems at non-cytotoxic concentrations. Astrocytes provide key metabolic and protective support to neurons during toxic challenge in vivo and generally the astrocyte containing cell systems showed increased tolerance to toxicant insult compared with the NT2.N mono-culture in vitro. Whilst there was no consistent relationship between MMP, ATP and GSH log IC(50) values for the NT2.N/A and NT2.A cell systems, these data did provide preliminary evidence of modulation of the acute neuronal toxic response by astrocytes. In conclusion, the suitability of NT2 neurons and astrocytes as cell systems for acute toxicity screening deserves further investigation.

KW - adenosine triphosphate

KW - analysis of variance

KW - astrocytes

KW - cell differentiation

KW - transformed cell line

KW - tumor cell line

KW - coculture techniques

KW - preclinical drug evaluation

KW - glial fibrillary acidic protein

KW - glutathione

KW - humans

KW - indicators and reagents

KW - inhibitory concentration 50

KW - mitochondrial membrane potential

KW - neurons

KW - neurotoxins

KW - oxazines

KW - spectrophotometry

KW - teratocarcinoma

KW - tubulin

KW - xanthenes

UR - http://www.scopus.com/inward/record.url?scp=77449103655&partnerID=8YFLogxK

UR - http://www.springerlink.com/content/c862803g74736444/

U2 - 10.1007/s12640-009-9084-3

DO - 10.1007/s12640-009-9084-3

M3 - Article

VL - 17

SP - 103

EP - 113

JO - Neurotoxicity Research

T2 - Neurotoxicity Research

JF - Neurotoxicity Research

SN - 1029-8428

IS - 2

ER -