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What makes our brain flexible? Researchers in Bayreuth investigate the plasticity of neurons

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University of Bayreuth, Press Release No. 133/2017, 3 November 2017

Since human and animal brains are capable of learning they can react to their environment. This is the case since their neurons are capable of altering and extending their function to deal with ever-changing requirements. The basis of this so-called neuronal plasticity is the possibility of electrical neuronal signals of being translated into genetic signals. Bayreuth researchers Dr. Claus-D. Kuhn (Biochemistry) and Prof. Dr. Gerrit Begemann (Developmental Biology) have now set out to investigate how this signal transformation occurs with an interdisciplinary project that was awarded 230,000 euros by the German Research Foundation (DFG). Their findings will be of great interest for the treatment of neuronal diseases.

Continuous neuronal stimulation in our brains has long-term effects on the molecular composition of our neurons. Special genes known as Immediate Early Genes (IEGs) are able to react to continuous electrical stimulation – they do so by instantaneously raising their own concentration in response to the stimulus. Such a sudden increase of IEGs in turn affects, which neuronal genes are translated into the ribonucleic acids (RNAs) and are thus used to produce essential proteins. From a biochemical perspective on can say that the increase in IEGs influences the neuronal gene expression patterns, i.e. the activities of many, yet distinct neuronal genes. Electrical signals thus become genetic signals. This process controls the development of an embryo’s brain and it allows the brains of children and adults to adapt to novel stimuli.

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Non-coding RNAs take the lead

Uncovering the causes of neuronal plasticity in our nerve cells requires extensive biochemical investigations in addition to the work carried out in zebrafish. The main focus of this work lies on genetic units known as enhancers, which are found all across the human genome.

“It is a well-known fact that enhancers influence gene activity by serving as docking platforms for transcription factors that bind to them in various combinations. In doing so, transcription factors prepare a gene for its transcription into RNA and its subsequent translation into a functional protein. However, only recently researchers discovered an additional factor that influences the activity of enhancers and might end up being key to understanding neuronal plasticity,” said Kuhn.

The exciting new factor is the discovery that enhancers, being DNA segments themselves, are also transcribed into RNAs. The resulting so-called enhancer RNAs do not contain the blueprints for proteins (which is why they are known as non-coding RNAs), however, they do play a major role in activating Immediate Early Genes. “The central topic of our project will be to study how enhancer RNAs activate IEGs and how these IEGs then in turn influence gene transcription rates and thus the production of essential neuronal proteins,” explains Kuhn.

The researchers expect the most long-lasting findings of the project from combining their molecular understanding of IEG activation by enhancer RNAs with their in vivo experiments in the nervous system of zebrafish: “It will be the crowning achievement of our project if we succeed in tracing the influence of enhancer RNAs during all stages of the development of the zebrafish brain,” says Begemann.

Funding

The German Research Foundation awarded funding for this project for three years as part of the DFG Priority Programme 1738 "Non-coding RNAs in Nervous System Development, Plasticity and Disease". The SPP 1738 program involves contributions from a total of 21 universities and research institutes across Germany.

Please see the following page for contact information.

Research in Bayreuth focussed on neuronal enhancer RNAs (eRNAs):

www.kuhnlab.uni-bayreuth.de/en/research/research_eRNAs


Contacts:

Dr. Claus D. Kuhn
Elite Network of Bavaria
Research Centre BIOmac
University of Bayreuth
D-95440 Bayreuth
Phone: +49 (921) 55-4356
E-mail: claus.kuhn@uni-bayreuth.de
www.kuhnlab.uni-bayreuth.de

Prof. Dr. Gerrit Begemann
Developmental Biology
University of Bayreuth
D-95440 Bayreuth
Phone: +49 (0)921 55 2475
E-mail: gerrit.begemann@uni-bayreuth.de
www.entwicklungsbiologie.uni-bayreuth.de


Editorial Office:

Christian Wißler
Press Contacts
University of Bayreuth
Universitätsstr. 30 / ZUV
95447 Bayreuth
Germany
Phone: +49 (0)921 / 55-5356
E-mail: christian.wissler@uni-bayreuth.de

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