Micro Electrode Arrays as a potential tool for in vitro neurotoxicity testing

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Apr 15, 2011
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Joint Research Centre publishes results from an inter-laboratory study

MEA At present neurotoxicity testing for regulatory purposes is based on in vivo animal test methods [1]. This approach includes high cost, long duration, low throughput, and is not always sensitive enough to predict human neurotoxicity. By November 2010 the REACH registrations of over 4000 chemicals were submitted to the European Chemicals Agency (ECHA). Most of them had not been tested for neurotoxic properties. Risk assessment of chemicals as well as the development of in vitro testing strategies for evaluating the neurotoxic hazard of chemicals is therefore a compelling issue of both political and regulatory interest.

In this context the European Commission's Joint Research Centre, Institute for Health and Consumers Protection (JRC-IHCP) is leading the first inter-laboratory study where the reproducibility of data on the neurotoxic effects of a set of compounds is assessed on neuronal in vitro cultures coupled to Micro Electrode Arrays (MEAs). The MEAs are devices that contain a plate (or multiple plates) embedded with printed electrodes serving as neural interfaces that connect cultured neurons to electronic circuitry. This configuration allows the recording and study of neuronal activity in a non-invasive and high throughput fashion (hundreds of recording points for each well). Since cultured neurons respond to neuroactive substances as well as the in vivo brain they constitute a valuable tool for investigating changes in the electrophysiological activity of the neurons in response to chemical exposures.

The laboratories participating in the inter-laboratory study belong to / are  the Italian Institute of Technology in Genova (I), the University of Rostock (D), the University of North Texas (Denton, US), the Environmental Protection Agency (Research Triangle Park, US) and to two SMEs: Neuroproof (Rostock, D) and ETT Solutions (Genova, I).

The first outcome of the study is very encouraging. The results obtained in the different laboratories are very homogeneous in spite of the slightly different adopted neuronal models and culture procedures. The intra- and inter-laboratory variabilities have been quantified and compared confirming the reproducibility of the data and the potential of this approach as neurotoxicity alternative test method.

The study was presented in March 2011 at the 50th Annual Meeting of the Society of Toxicology in Washington D.C. (US) and is accepted for publication in Frontiers in Neuroengineering.

Read more:

Novellino A., Scelfo B., Palosaari T., Price A., Sobanski T,. Shafer T.J., Johnstone A.F., Gross G.W., Gramowski A., Schroeder O,. Jügelt K., Chiappalone M., Benfenati F., Martinoia S., Tedesco M.T., Defranchi E., D'Angelo P. and Whelan M. (2011). Development of micro-electrode array based tests for neurotoxicity: assessment of interlaboratory reproducibility with neuroactive chemicals. Front. Neuroeng. 4:4. doi: 10.3389/fneng.2011.00004

Photo: MEA setup general overview and complete setup - IHCP Assay technologies and HTS - Copyright European Union 2010


[1] OECD Test Guidelines TG481, TG419, TG424 and TG426 and EPA Guidelines for Neurotoxicity Risk Assessment: FRL 6011-3.