Navigation Links
Exercise rescues mutated neural stem cells

CHARGE syndrome* is a severe developmental disorder affecting multiple organs. It affects 1 in 8500 newborns worldwide. The majority of patients carry a mutation in a gene called CHD7. How this single mutation leads to the broad spectrum of characteristic CHARGE symptoms has been a mystery.

CHD7 encodes a so-called chromatin remodeler, an important class of epigenetic regulators. DNA is wound around bead-like nucleosomes consisting of histone proteins. The string of beads is then twisted into a structure called chromatin. The more nucleosomes that occupy a gene, the less active it is. Chromatin remodelers like CHD7 are essential for the regulation of gene activity because they create nucleosome-free regions in the regulatory sequences of genes. Thus, a mutation in a gene coding for a chromatin remodeler may lead to a wide pattern of misregulated genes.

Dr. Haikun Liu's lab at the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) is interested in the regulation of adult neural stem cells. The scientists have a particular focus on the role adult neural stem cells play in human diseases, including mental retardation and brain tumors. CHARGE patients suffer from mental retardation and learning disabilities, strongly suggesting that a central nervous defect underlies the disease.

To understand the molecular role of the CHD7 mutation in the CHARGE phenotype, the researchers created a model using genetically modified mice. These animals permit the scientists to switch off the CHD7 gene uniquely in neural stem cells at specific developmental stages. This permitted the scientists to follow how CHD7-deficient cells proliferate, differentiate and mature over the entire lifespan of the animal.

The work led to an exciting finding: by switching off CHD7 in either fetal or adult neural stem cells, the scientists observed that the mutant cells behaved in a common way: They could not efficiently differentiate into mature 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 role in other types of cells.


Contact: Dr. Sibylle Kohlstädt
Helmholtz Association of German Research Centres

Related biology news :

1. Total amount of exercise important, not frequency, research shows
2. Gene offers an athletes heart without the exercise
3. Exercise for stroke patients brains
4. Epigenetic biomarkers may predict if a specific diet and exercise regimen will work
5. Serotonin mediates exercise-induced generation of new neurons
6. Exercise or make dinner? Study finds adults trade one healthy act for another
7. Amiigo Unveils Fitness Tracker That Knows What Exercise Youre Performing
8. For those short on time, aerobic, not resistance, exercise is best bet for weight, fat loss
9. Exercise is smart for your heart - and makes you smarter
10. Exercise boosts satisfaction with life, researchers find
11. American Physiological Societys latest conference focuses on integrative biology of exercise
Post Your Comments:
(Date:10/29/2015)... , Oct. 29, 2015 Daon, a ... that it has released a new version of its ... in North America have already ... v4.0 also includes a FIDO UAF certified server ... already preparing to activate FIDO features. These customers include ...
(Date:10/29/2015)... , October 29, 2015 ... biometric authentication company focused on the growing mobile ... wallet announces that StackCommerce, a leading marketplace to ... featuring the Wocket® smart wallet on StackSocial for ... ) ("NXT-ID" or the "Company"), a biometric authentication ...
(Date:10/27/2015)... October 27, 2015 Munich, ... Gaze Mapping technology (ASGM) automatically maps data from mobile ... Glasses , so that they can be quantitatively ... Munich, Germany , October 28-29, 2015. ... data from mobile eye tracking videos created with ...
Breaking Biology News(10 mins):
(Date:11/25/2015)... November 25, 2015 The ... is a professional and in-depth study on the ...      (Logo: ) , ... industry including definitions, classifications, applications and industry chain ... the international markets including development trends, competitive landscape ...
(Date:11/24/2015)... Nov. 24, 2015 Cepheid (NASDAQ: CPHD ... at the following conference, and invited investors to participate ...      Tuesday, December 1, 2015 at 11.00 a.m. ...      Tuesday, December 1, 2015 at 11.00 a.m. ... New York, NY      Tuesday, December ...
(Date:11/24/2015)... (PRWEB) , ... November 24, 2015 , ... ... event of the year and one of the premier annual events for pharmaceutical ... ran from 8–11 November 2015, where ISPE hosted the largest number of attendees ...
(Date:11/24/2015)... ... ... This fall, global software solutions leader SAP and AdVenture Capital brought together ... their BIG ideas to improve health and wellness in their schools. , Now, the ... title of SAP's Teen Innovator, an all-expenses paid trip to Super Bowl 50, and ...
Breaking Biology Technology: