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Open Access Dysfunction and microRNA regulation abnormality in next generation neural stem cells due to nanoparticle exposure

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Tachibana and his team have shown that nanoparticles have a negative effect on the neural development of mice. Since then, they have been working to find the method to investigate this effect on neural development. They have uncovered that the particles somehow act to alter gene expression. RNA screens show that levels of certain mRNAs are altered by neural stem cells’ exposure to nanoparticles. They have also observed a related significant change in how neurotransmitters are made and processed. Neurotransmitters are the signalling molecules responsible for communication between neurons. Their concentrations and recycling in the cell are carefully regulated by the neuron. Disrupting that balance can have very negative effects. For example, Tachibana and his team have shown that levels of dopamine and its metabolites are altered after exposure to nanoparticles. This could have potentially huge downstream effects on mental health in later life. The picture Tachibana is building has become more complex in recent years. He has begun to notice the role of microRNAs in the impact of nanoparticles. MicroRNAs are small sequences of RNA that play a vital role in modulating gene expression in the cell. The exposure of the mother to nanoparticles leads to changes in the levels of certain microRNAs. Tachibana explains the downstream effects of this: ‘We used bioinformatics to model the microRNA targets and looked at the function of these targets. We found that this microRNA regulates genes associated with the differentiation of neural cells and memory function, both essential processes in development.’ The next steps of the project are currently in the planning stages in Tachibana’s lab. Since proving nanoparticles are exerting a significant effect on neural development through microRNAs, the next step is to look at the effect on developed mice. Mice typically continue their neural development for about three weeks after birth. Therefore, Tachibana and his team are looking to conduct a longer-term experiment whereby they follow exposed mice into adulthood and examine the effect of the particulates. From this, they will be able to elucidate how gene expression levels change in the exposed mice compared to controls. In addition, they will be able to observe a phenotypic effect, that is to say a measurable difference such as the cognition of the different mice.
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Keywords: ALTER GENE EXPRESSION; BIOCHEMICAL AND GENETIC ANALYSES; BIOINFORMATICS; COGNITION; DOPAMINE; MATERNAL NANOPARTICLE EXPOSURE; MEMORY FUNCTION; METABOLITES; MODEL THE MICRORNA TARGETS; MODULATING GENE EXPRESSION; MRNAS; NANOPARTICLES; NEURAL DEVELOPMENT; NEURAL STEM CELLS EXPOSURE TO NANOPARTICLES; NEUROTRANSMITTERS; RNA SCREENS

Document Type: Research Article

Publication date: March 1, 2019

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