FAU researchers develop a procedure for examining the effects of chemical substances on the central nervous system (CNS)
One of the latest research projects at FAU kills two birds with one stone: a working group at the Institute of Medical Biotechnology is developing a procedure that will allow for chemical substances to be examined for toxic effects in vitro, saving costs and time compared with the animal experiments used so far. The procedure is also a contender for an alternative to animal experiments.
Learning difficulties and developmental disorders – such as attention deficit/hyperactivity disorder (ADHD) or autism – have been growing more frequent for some years. The exact cause for this increase is currently still unknown. Scientists assume that environmental pollutants such as heavy metals and pesticides are responsible for the disorders – but it could just as well be one of the more than 70 million other chemical substances listed in the CAS Registry, the world’s largest database of chemical substances, and which can be found in everyday products such as packaging materials, electrical appliances, cleaning agents, or preservatives in food.
Only a fraction of these substances has been tested for harmful effects on the maturing central nervous system (CNS): the requirements for the test procedures that help to assess the hazard potential to the CNS are very high, cost-intensive, time-consuming and not mandatory. The substances are only tested for side effects as required by legislation, such as skin rashes or eye irritation. The approach used in these procedures is also problematic: chemical substances are mainly tested for their toxicity in animal experiments. Since the physiology of animals and humans can vary to a large degree depending on the animal, it is possible that substances found to be harmless to an animal can still turn out to be hazardous to humans. A prime example of this is the drug thalidomide, which was found to be non-hazardous to animals but led to severe birth deformities in humans.
Efficient combination in test tubes
In ‘Developmental Neurotoxicity Testing’ (DNT), the test procedure used so far to examine the effects of chemical substances on thematuring CNS, pregnant rats were repeatedly exposed to a substance and mother and offspring were monitored for irregular behaviour. The working group led by Dr. Daniel Gilbert and Prof. Oliver Friedrich is now researching how DNT can be replaced with an in vitro procedure. The researchers are aiming for the development of a high-throughput screening approach: this is an automated method in which the effects of substances on cells are tested in a test tube in a very short time and in large number – hence the term high-throughput.
The basis for the new test procedure are human stem cells. The scientists let them mature into cells of the central nervous system in cell cultures before exposing them to toxic substances in a controlled setting. A combination of various analytical methods is to reflect the toxic effects on different levels. In the first step, the procedure analyses the structure of the newly-bred nerve cells. The matured cells form a widely ramified network which determines the functional qualities of the CNS and thus influences our behaviour. This analysis may serve as an indicator for behavioural disorders such as ADHD. In the second step, the procedure is supposed to examine whether the substances have a toxic effect on the nerve cells. The researchers will focus on proteins that control the transmission of stimuli between the cells, as epilepsy or muscle cramps may be caused if this communication is interrupted. ‘By combining these two procedures which are normally used independently, we aim to make reliable predictions regarding the toxicity of chemical substances. Considering the sharp increase in neurological disorders, the development of efficient test series is vital,’ Gilbert explains.
Dr. Daniel Gilbert
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Prof. Dr. Dr. Oliver Friedrich