When it comes to royalty, things are clear: The king’s first child inherits the crown. Siblings born later should take up less glamorous professions. This is pretty much the same for some nerve cells in the brain. In their case, it is not the order in which they are born, but at least the time of their emergence that determines their further career. This is according to a recent study from the University of Bonn. The results were obtained in rats; So the extent to which they can be transferred to humans is still uncertain. They are now published in the magazine e-neuro,
In their study, the researchers examined a specific type of cell: dopaminergic neurons in the midbrain. They have a somewhat cumbersome name because of their ability to produce dopamine. This messenger substance plays an essential role in signal transmission between certain nerve cells. The loss of dopaminergic neurons can therefore lead to Parkinson’s disease, for example, with its characteristic deficits in movement sequences.
Not all dopaminergic neurons in the midbrain are the same. “We now know a whole range of different types, all of which serve specific functions in the brain,” explains Professor Dr Sandra Blass from the Institute for Reconstructive Neurobiology at the University Hospital Bonn. “They send very long nerve fibers, called axons, to different areas of the brain. One of the things they carry through these fibers to the corresponding target area is dopamine.” Nevertheless, most of these types probably arise from the same progenitor cells. “We wanted to know how these progenitors developed into different groups of dopaminergic cells without which the brain would not function.”
Time to emerge decides career path
It has been known for some time that the career of other nerve cells depends on the time of their emergence. “We investigated whether this is also the case in dopaminergic neurons,” says Alessandro Petiz, who is a professor at Prof. Blass’s group is doing a doctorate. “In mice, it takes four to five days for all progenitor cells to turn into dopaminergic neurons. We wanted to know: Do the neurons that form on the first day differentiate as early as day two, three or four?”
To do this, the researchers labeled precursor cells at different times so that all neurons that were released from these precursors turned green under a microscope on subsequent days. In contrast, neurons that had previously emerged from unlabeled precursors remained dark. “In this way, we found that early-born cells can still develop into all types of dopaminergic neurons in the midbrain,” says Blais’s colleague, Franca Fries. Figuratively speaking, these cells can still follow very different career paths. “However, the later they are born, the narrower their options. So the more specialized they become.”
Basic research with relevance to practice
The research group now wants to investigate which signals force progenitor cells to rapidly move in a certain direction. “In reconstructive neurobiology, there are now efforts to make neurons from stem cells,” says Blais, a member of the Transdisciplinary Research Area “Life and Health” at the University of Bonn. “This is because it allows for the targeted reproduction of nerve cell types in the laboratory, which could potentially be used to reverse the loss of cells that occurs in Parkinson’s disease, for example.” To do this, it is important to understand the processes that occur during natural differentiation.
The study results may also make it possible to specifically turn off certain types of dopaminergic cells in mice. This may provide new insights into the mechanisms of various diseases in which alterations in the dopaminergic system play a role – from depression to schizophrenia to Parkinson’s disease.
The study was funded by the German Research Foundation (DFG) and the Maria von Linden program of the University of Bonn.
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