Particularly in Alzheimer's disease, nerve cell degeneration plays a crucial role. In the future, new therapeutic options may possibly be derived from steering the generation and/or migration mechanism. These findings have been published in the current issue of the renowned journal Nature Neuroscience. Until only a few years ago, neurogenesis – the process of nerve cell development – was considered to be impossible in the adult brain. The textbooks asserted that dead nerve cells could not be replaced. Then researchers discovered regions in the forebrain in humans in which new nerve cells can be generated throughout life. These so-called GABAergic cells use gamma-aminobutyric acid (GABA), a neurotransmitter of the central nervous system.
A research team of scientists led by Magdalena Götz, director of the Institute of Stem Cell Research at Helmholtz Zentrum München and chair of the Department of Physiological Genomics of LMU, has now taken a closer look at this brain region in the mouse model. Their findings: Even in the forebrain, there are other nerve cells that are regularly generated – the so-called glutamatergic nerve cells, which use glutamate as neurotransmitter. The stem cell researchers could prove this by means of a specific transcription factor: Tbr2 is only present in progenitor cells of glutamatergic nerve cells.
The newly generated nerve cells in the adult organism are located in the olfactory bulb, the region of the brain involved in the sense of smell. Nerve cells that use glutamate as a neurotransmitter are also responsible for memory – storing and retrieving information. In Alzheimer dementia, alterations in the signal transduction pathways of these special cells play a significant role.
Magdalena Götz explained the reason why this finding is so important: "Neural progenitor cells can generate these newly discovered glutamatergic nerve cells for the neighboring cerebral cortex – for example after brain injury." The research group was able to demonstrate this on the mouse model: There the cells migrated into the damaged neighboring cerebrum tissue and generated mature neurons. Accordingly, progenitor cells could then replace degenerate nerve cells.
"Now it will be interesting to find out whether this process also takes place in humans, particularly in Alzheimer's patients," said Magdalena Götz, "and also whether the process can be kept under control to avoid massive cell death." One therapeutic approach would then be to attempt to stimulate the body's own replacement mechanism.
Further Information
Original Publication:: Monika S Brill, Jovica Ninkovic, Eleanor Winpenny, Rebecca D Hodge, Ilknur Ozen, Roderick Yang, Alexandra Lepier, Sergio Gascón, Ferenc Erdelyi, Gabor Szabo, Carlos Parras, Francois Guillemot, Michael Frotscher, Benedikt Berninger, Robert F Hevner, Olivier Raineteau & Magdalena Götz: Nature Neuroscience, Volume 12 No 11 pp1351-1474 (doi:10.1038/nn.2416)
Helmholtz Zentrum München is the German Research Center for Environmental Health. As leading center oriented toward Environmental Health, it focuses on chronic and complex diseases which develop from the interaction of environmental factors and individual genetic disposition. Helmholtz Zentrum München has around 1680 staff members. The head office of the center is located in Neuherberg to the north of Munich on a 50-hectare research campus. Helmholtz Zentrum München belongs to the Helmholtz Association, Germany's largest research organization, a community of 16 scientific-technical and medical-biological research centers with a total of 26,500 staff members.
The Institute of Stem Cell Research of Helmholtz Zentrum München investigates the cellular and molecular mechanisms which regulate cell fate and cell proliferation in different organ systems. The scientists investigate the stem cells of different organs, e.g. of the nervous system or of the blood and immune systems in order to elucidate the molecular and cellular mechanisms that are responsible for the common features of all stem cells, such as multi-potency and self-renewal. Another research focus is the regulation of the genesis of specific cell types from stem cells with respect to cell replacement therapy.
Editor: Sven Winkler, Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Ingolstädter Landstraße 1 85764 Neuherberg Tel.: 089-3187-3946, Fax 089-3187-3324, Internet: www.helmholtz-muenchen.de, E-Mail: presse@helmholtz-muenchen.de
Journal
Nature Neuroscience