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Exercise rescues mutated neural stem cells
Date:7/5/2013

re neurons, which are the basic functional unit in the brains of humans and other animals. Mature neurons normally have a very complex morphology, allowing them to create networks in the brain which are important for processing information. Neurons with the mutant form of CHD7, however, seem to be incapable of forming networks.

Most strikingly, Liu and colleagues found that exercise fully rescued this phenotype in the hippocampus, the core region of the brain responsible for learning and memory. They allowed the CHD7 deficient animals to exercise on a running wheel, which rodents love to do. After the running exercise the CHD7 mutant neurons were fully rescued: They were able to create functioning networks.

That running causes a dramatic increase in neurogenesis in adults has been confirmed in animals and humans. "We were extremely excited to see that the CHD7 deficiency in a cell can be bypassed via an unknown mechanism provoked by exercise involving running. Now, we are eagerly working to find the underlying mechanism," says Haikun Liu. The neuroscientist believes this discovery will lead to a better understanding of the disease, possibly even pointing to a way to reactivate the CHD7 pathway and thus to attenuate CHARGE symptoms in human patients.

CHD7 is also an important cancer-related gene; many different types of human cancers, including lung cancer, colon cancer and brain tumors exhibit mutations in the molecule. The mechanism identified here provides a clear explanation: A mutation in CHD7 leads to a blockage of differentiation in stem cells, which is a major cause of tumorigenesis.

In addition, CHD7 has been identified as a high-risk gene in human autism, and many CHARGE patients are autistic. It seems that the gene is important in the regulation of many more physiological processes in the body. By analogy to the neural stem cell study, the DKFZ researchers will now use their advanced mouse model to investigate CHD7's
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Contact: Dr. Sibylle Kohlstädt
s.kohlstaedt@dkfz.de
Helmholtz Association of German Research Centres
Source:Eurekalert

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