How do nerves grow with age

How are new nerve cells formed in the brain?

Nerve cells, so-called neurons, can also form new in the brain of adults. However, this important finding is still relatively new: It has only been scientifically proven since the beginning of this millennium that even after early childhood, new neurons can develop from the cells that support the nerve tissue, the glial cells. Professor Magdalena Götz contributed to this finding: She was able to prove that there are certain areas in the brain in which these so-called adult stem cells arise. Thereafter, their offspring migrate to other areas, where they mature into full-fledged neurons and can be integrated into the neural network. This knowledge has revolutionized neurobiology.

Since then, the professor, who meanwhile heads the Physiological Genomics Department at the Biomedical Center of the Ludwig Maximilians University in Munich and the Institute for Stem Cell Research at the Helmholtz Zentrum München, has been investigating the factors that influence this so-called neurogenesis.

Stem cell niches - the nursery in the brain

In the adult mammalian brain, nerve stem cells are only found in certain areas, the so-called stem cell niches. What makes these regions so special? To find out, Götz and her team examined the proteome of these niches for the first time - that is, the entire amount of proteins present there. To do this, they examined two regions in more detail: On the one hand, the largest stem cell niche in the brain in the so-called subventricular zone. The brain contains several chambers or ventricles that are filled with cerebrospinal fluid. The walls of these ventricles are lined with a special type of cell. Underneath is the subventricular layer with the neural stem cells. On the other hand, the researchers examined the olfactory bulb in the front part of the brain, as newly formed neurons migrate here, differentiate themselves there and integrate into the neural network. In the mouse brain, Götz's team compared these niche proteomes with the proteome of other brain regions in which no neurogenesis takes place and no new nerve cells are integrated. In doing so, they discovered central differences that point to regulators for the formation of neurons.

One feature of stem cell niches that the researchers describe in the renowned science journal “Cell Stem Cell” is that these regions are particularly rigid and not very flexible. One of the reasons for this is that the extracellular matrix, i.e. the cell components that adhere to the outside of the cell, form a strong network. This prompted the scientists to examine these components more closely. They found out that, for example, a special enzyme - transglutaminase 2 - plays a crucial role in regulating neurogenesis.

Knowledge of such differences in the proteome of neurogenic and non-neurogenic brain regions forms the basis for improving the future treatment of diseases in which nerve cells are destroyed - severe traumatic brain injuries, for example.

In the next step, Götz and her team will therefore compare the analyzed proteomes with those of injured brain regions. “One of our colleagues at the University of Cambridge found that the scar tissue in the brain is particularly soft - an unfavorable environment for neurogenesis. We have to overcome this hurdle. We need to create an environment that is suitable for repairing damaged brain regions. We will continue to research this, ”explains Götz.

Funding and researching together: European research networks

Prof. Magdalena Götz's project is part of a European research network. Research groups from Germany, Belgium, the United Kingdom and Poland work together here. They are funded by a European research network, the ERA-Net NEURON, in which the Federal Ministry of Education and Research (BMBF) has joined forces with other funding organizations from many European countries.

Original publication

J. Kjell et al: Defining the adult neural stem cell niche proteome identifies key regulators of adult neurogenesis. Cell Stem Cell 2020, doi: 10.1016 / j.stem.2020.01.002.

Review article

Roger A. Barker, Magdalena Götz, Malin Parmar, New approaches for brain repair — from rescue to reprogramming. Nature 2018, doi: 10.1038 / s41586-018-0087-1