Changing dead neurons to new ones

Stem cells can successfully replace dead brain cells

Anastasia Krasnianskaya, Geektimes

Researchers from the Ludwig-Maximilian University of Munich, the Max Planck Institute of Neurobiology, and the Research Center named after Helmholtz in Munich demonstrated that in mice, transplanted neurons derived from embryonic cells can actually be incorporated into an existing network and correctly perform the tasks for which the damaged cells were responsible. This work is of great importance in the potential treatment of all acquired brain diseases, including strokes, injuries, neurodegenerative diseases like Alzheimer's or Parkinson's. Each of these ailments leads to irreversible loss of nerve cells and lifelong neurological deficit.

When it comes to recovery, for example, after a stroke, the adult brain has very little capacity to compensate for lost nerve cells. Therefore, doctors and researchers in the field of biomedicine are exploring the possibility of using transplanted nerve cells to replace neurons that have suffered as a result of injury or illness. Previous studies show that it is possible to eliminate at least some clinical symptoms by transplanting fetal nerve cells into damaged neural networks. However, the process of obtaining fetal cells raises many ethical questions, since this biomaterial can only be obtained from the fetus after an abortion, approximately at 9-12 weeks of pregnancy. In addition, it is not completely clear whether the transplanted intact neurons will be able to integrate well enough to restore the functions of the neural network.

In a study published in the journal Nature on October 26 (Falkner et al., Transplanted embryonic neurons integrate into adult neocortical circuits), scientists found out whether it is possible to transplant embryonic nerve cells so that they successfully integrate into the neural network and function in the visual cortex of adult mice. "We know so much about the functions of nerve cells in this area that we can easily assess whether the implanted cells actually perform the tasks assigned to the neural network," says Professor Mark Huebener, one of the leaders of the study. Huebener specializes in the structure and functions of the mammalian visual system.

In their experiments, the research team transplanted embryonic cells into the affected areas of the visual zone of adult mice. Over the following months, they observed the behavior of implanted immature neurons using two-photon microscopy. This method helped to find out whether they differentiate into so—called "pyramidal cells" - excitatory neurons. The fact that the cells survived and continued to develop is very encouraging. Everything became more interesting when the researchers took a closer look at the electrical activity of the transplanted cells. A joint study by graduate student Suzanne Faulkner and postdoctoral researcher Sofia Grade showed that the new cells formed synaptic connections that are usually established between network cells and responded to visual stimuli.

Nerve grafts (blue)
they communicate with undamaged sections of the network (yellow)

The team then continued to study the established connections after the neuron transplant. They found that pyramidal cells derived from transplanted mature neurons formed functional connections with corresponding nerve cells throughout the brain. In other words, they have successfully taken the place of their predecessors. In addition, they were able to process incoming information and transmit it further over the network. "These results show that the implanted nerve cells were combined with exceptional accuracy into a neural network, which, under normal conditions, would never have included new nerve cells," explains Professor Magdalena Goetz, whose job was to find ways to replace the lost neurons in the central nervous system. A new study shows that immature neurons are able to correctly respond to signals in the brain of adult mammals and can close functional "gaps" in the existing neural network.

One of the main advantages of transplantation of embryonic stem cells is that they do not produce tissue compatibility antigens. When the sets of antigens in the donor and recipient do not match, this leads to cell rejection. But in the case of ESK transplantation, this does not happen, and the chance that the cells will take root is usually very high. However, scientists have found out that there are mechanisms that can prevent the engraftment of new cells.

The process of creating neurons from stem cells and progenitor cells is called "neurogenesis". Scientists have shown that epigenetic mechanisms that come into play at the early stages of neurogenesis have a significant impact on the future fate of novice neurons. These mechanisms affect inherited changes in the phenotype or gene expression, but do not lead to a change in the DNA sequence. To find out what significance early epigenetic modifications have on the development of nerve cells during embryogenesis in mice, Magdalene Goetz and her colleagues purposefully blocked the activity of the UHRF1 gene. The gene controls many epigenetic functions, including DNA methylation — modification of a DNA molecule without affecting the sequence of nucleotides. Methylation of certain nucleotide bases in DNA often serves to "turn off" certain genes.

Blocking of UHRF1 in the anterior region of the rat brain led to activation of retroviral elements in the genome, which had previously been suppressed by methylation. Activation caused the accumulation of retroviral proteins in the affected cells and the deregulation of genes. This, in turn, led to progressive disturbances in vital cellular processes and accelerated the mass death of cells. The results of this study showed that even such factors, which act only at the very beginning of neurogenesis, are able to influence the fate of cells, which can manifest itself only weeks later.

Portal "Eternal youth" http://vechnayamolodost.ru  01.11.2016