How is the brain cell replaced

New brain cells against Parkinson's

Brain cells can die, but cannot grow back, that was the credo of brain researchers for a long time - a "repair of the brain" in the case of neurodegenerative diseases such as Parkinson's disease is therefore impossible. A few years ago, however, it became apparent that stem cells are also able to produce new neurons in the brain of people well into old age. This discovery is linked to the bold hope of developing an “antidote” for cell death in the brain, which is associated, for example, with Parkinson's disease or a stroke.

In the middle of 2004, Dr. Günter Höglinger, neurologist at the Philipps University of Marburg, together with a Paris research group, presented a work in the journal Nature Neuroscience in which it was demonstrated that the messenger substance dopamine can stimulate neural stem cells of rodents in such a way that new, functioning brain cells arise (see www .online.uni-marburg.de / zv / news / presse / 2004-06-14.html). Around Höglinger, a dynamic group of young researchers has now emerged in the Biomedical Research Center of Philipps University, which places a major focus of its work on Parkinson's disease on the importance of the body's own stem cells for repair processes in the brain.

In the renowned journals Journal of Neuroscience and Brain, members of the research groups in Marburg and Paris have now published two further publications, which on the one hand confirm their results in experiments on primates and on the other hand reveal a previously unknown self-help mechanism of the brain.

In the Journal of Neuroscience, medical student Nils Freundlieb and Dr. Günter Höglinger, together with colleagues from the Institut de la Santé et de la Recherche Médicale (INSERM), Paris, for the first time about the fact that the neurogenesis process in primates is also influenced by the messenger substance dopamine. “Up to now it was only known from rodents,” explains Freundlieb, “that regulatory factors such as dopamine are closely related to the formation of new brain cells. We have now been able to confirm this result in primates and thus for the first time demonstrate a molecular influencing mechanism of neurogenesis in primates. You can't get any closer to humans with animal experiments. "

The researchers administered the Parkinson poison MPTP to their test animals. As in Parkinson's disease, it prevents the brain from being supplied with sufficient amounts of dopamine. The subventricular zone (SVZ), which is the largest reservoir of neural stem cells in many animals, also suffers from a dopamine deficiency. “We have proven,” says Freundlieb, “that the reduced dopamine level in the SVZ means that the neural stem cells only produce new brain cells to a greatly reduced extent. Dopamine therefore also plays a decisive role in neurogenesis in the brain in primates. ”The researchers now hope that their findings can be used in the long term to develop therapies that stimulate the brains of Parkinson's patients in such a way that destroyed nerve cells can be replaced by new ones.

Almost at the same time, a work appeared in the specialist journal Brain, in which Günter Höglinger and Nils Freundlieb were also significantly involved. Together with researchers from INSERM, the Marburg neurologists were able to prove for the first time that the brain of primates has a previously unknown self-help mechanism that counteracts the death of brain cells in the course of Parkinson's disease. "We found," explains Freundlieb, "that certain nerve cells in the brain that otherwise produce the messenger substance GABA suddenly start producing dopamine in the course of the disease." In view of the dopamine deficiency that typically occurs in Parkinson's disease, this is effective So the brain to help itself.

"We have shown a completely new principle of self-repair of the brain, a so-called 'phenotypic transdifferentiation' of mature nerve cells. But because only very few of these 'GABAergic microneurons' spontaneously switch to dopamine production, we are now looking for a mechanism that could specifically intensify this process. ”With their work, the scientists refuted other publications in which it was speculated that these dopamine-producing nerve cells would emerge from stem cells in the course of the disease. “In fact,” says Höglinger, “they already exist before, but they expand their area of ​​responsibility. It's like brick-making factories suddenly bake cakes in the face of famine to make up for the shortage. "

In the meantime, the young research group is devoting itself to numerous other questions. "Of course, we want to know more precisely what the function of controlling the formation of new nerve cells in the adult brain with dopamine means", says Höglinger. “It could very well be that certain symptoms of Parkinson's disease such as depression, olfactory disorders and decreased memory performance can actually be traced back to the reduced formation of new brain cells. The mechanisms we have proven could also play important roles in other diseases such as schizophrenia or addiction. ”Höglinger suspects that many of these relationships are highly probable,“ but so far no one has been able to prove them. ”

Original publications

Journal of Neuroscience: Freundlieb N, François C, Tandé D, Oertel WH, Hirsch EC, Höglinger GU. "Dopaminergic Substantia Nigra Neurons Project Topographically Organized to the Subventricular Zone and Stimulate Precursor Cell Proliferation in Aged Primates" J. Neurosci. 2006 26: 2321-2325; doi: 10.1523 / JNEUROSCI.4859-05.2006 (February 22, 2006)

Brain: Tandé D, Höglinger GU, Debeir T, Freundlieb N, Hirsch EC, François C .: “New striatal dopamine neurons in MPTP-treated macaques result from a phenotypic shift and not neurogenesis” Brain (2006), doi: 10.1093 / brain / awl041 ; Brain Advance Access (February 15, 2006)

The homepage of the Marburg research group will also go online in the next few days: www.exp-neuro.de

Contact

Dr. Günter U. Höglinger
Philipps University of Marburg
Biomedical research center
Experimental neurology
Hans-Meerwein-Strasse
35032 Marburg

as

Department of Neurology
Director: Professor Dr. Wolfgang H. Oertel
Rudolf-Bultmann-Str. 8th
35033 Marburg

Tel .: (06421) 28 66088
e-mail