Running stimulates neurogenesis

CHARGE syndrome is the acronym for a rare genetic disease that includes several defects: coloboma, heart defects, atresia choanae, retardation, genital and urinary tract defects and ear abnormalities. This syndrome is caused by mutation of a gene that is found on chromosome 8, called CHD7, which plays an important role in the activation and deactivation of other genes. Not many details are known about the mutation of this gene even though it is known that it leads to a wide range of defects. It should be noted that CDH7 is implicated in several cancers; colon cancer, lung or brain tumors express mutations of this gene.

It seems that CHD7 encodes an epigenetic regulator that plays an important role in remodeling of chromatin and nucleosomes (which are DNA structures). Epigenetic regulators like CDH7 are essential for creating some nucleosome-free regions in the gene structure. Therefore, the mutation of CDH7 may cause other misregulated genes. Haikun Dr. Liu’s lab at the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), is investigating adult neural stem cells and their role in human diseases such as brain tumors and mental retardation. A group of patients with mental retardation and developmental disabilities are the patients with CHARGE syndrome. And it seems that what underlies this syndrome is a central nervous defect.

To better understand the role of CDH7 mutation in CHARGE syndrome, the researchers made several experiments on genetically modified mice. They switched off uniquely CHD7 gene in neural stem cells in different stages of neurodevelopment, allowing researchers to see how cells evolve without CDH7. Scientists have observed that in both fetal and adult neural stem cells, switching off CHD7 prevented cells to develop into mature neurons, which are morpho-functional units of the brain. Neurons are complex structures that are interconnected by synapses, which form networks in the brain. It seems that the mutant form of CHD7 prevent neurons to form these networks.

What is interesting is that the researchers found that exercise resulted in the recovery of CHD7 deficient animals. After practicing on a running wheel, rodents were completely recovered. The role of running in neuronogenesis was demonstrated in both animals and humans. Researchers now believe that this discovery will lead to a better understanding of CHARGE syndrome and a potential treatment to improve symptoms in 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.