Brain-derived neurotrophic factor as an indicator of chemical neurotoxicity: an animal-free CNS cell culture model

Elizabeth K. Woehrling, Eric J. Hill, David Nagel, Michael D. Coleman

Research output: Contribution to journalArticle

Abstract

Recent changes to the legislation on chemicals and cosmetics testing call for a change in the paradigm regarding the current 'whole animal' approach for identifying chemical hazards, including the assessment of potential neurotoxins. Accordingly, since 2004, we have worked on the development of the integrated co-culture of post-mitotic, human-derived neurons and astrocytes (NT2.N/A), for use as an in vitro functional central nervous system (CNS) model. We have used it successfully to investigate indicators of neurotoxicity. For this purpose, we used NT2.N/A cells to examine the effects of acute exposure to a range of test chemicals on the cellular release of brain-derived neurotrophic factor (BDNF). It was demonstrated that the release of this protective neurotrophin into the culture medium (above that of control levels) occurred consistently in response to sub-cytotoxic levels of known neurotoxic, but not non-neurotoxic, chemicals. These increases in BDNF release were quantifiable, statistically significant, and occurred at concentrations below those at which cell death was measureable, which potentially indicates specific neurotoxicity, as opposed to general cytotoxicity. The fact that the BDNF immunoassay is non-invasive, and that NT2.N/A cells retain their functionality for a period of months, may make this system useful for repeated-dose toxicity testing, which is of particular relevance to cosmetics testing without the use of laboratory animals. In addition, the production of NT2.N/A cells without the use of animal products, such as fetal bovine serum, is being explored, to produce a fully-humanised cellular model.

LanguageEnglish
Pages503-511
Number of pages9
JournalAlternatives to Laboratory Animals
Volume41
Issue number6
Publication statusPublished - Dec 2013

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Brain-Derived Neurotrophic Factor
Neurology
Cell culture
Animals
Central Nervous System
Cosmetics
Cell Culture Techniques
Testing
Chemical hazards
Level control
Nerve Growth Factors
Neurotoxins
Laboratory Animals
Cell death
Cytotoxicity
Coculture Techniques
Legislation
Immunoassay
Astrocytes
Neurons

Keywords

  • astrocyte
  • BDNF
  • brain-derived neurotrophic factor
  • central nervous system
  • in vitro
  • neuron
  • neurotoxicity
  • NT2.N/A
  • serum-free

Cite this

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