miRNA as a marker for in vitro neurotoxicity testing and related neurological disorders

Abstract

miRNA (miRNAs) are small noncoding RNA molecules, which bind to the 3′UTR of target mRNA and thereby posttranscriptionally regulate gene expression. Thus, miRNA are important fine-tuners of essential processes in the body. In the brain, they regulate neural development and brain homeostasis. Studying miRNA profiling in combination with whole genome transcriptomics after toxicant exposure is a prime way to derive molecular signatures of toxicity. This gives an insight into molecular network perturbations, which underlie systems toxicology. miRNA encapsulated into extracellular vesicles are released into biofluids and in case of in vitro systems into the culture medium as means of intercellular communication but also in response to environmental stress. In addition, miRNA are released into the circulation upon organ injury. Thus, circulating miRNA may serve as potential biomarkers of (brain) injury/toxicity. In this chapter, the importance of miRNA for neural development, neurotoxicity, and neurodegeneration is discussed; the critical steps of miRNA profiling in tissues/cells as well as in biofluids are described; the challenges and options of bioinformatic data analysis are deliberated. The focus of this chapter is on the quality control of miRNA profiling methods.