Will astrocytes help with spinal cord injury?
Spinal cord neurons have been restored in a living organism
Maybe even in a wheelchair.
Scientists, however, are stubbornly looking for ways to restore spinal cells. The most obvious way is probably connected with the use of stem cells – so that they turn into neurons and eliminate the damage. However, researchers from the Southwest Medical Center at the University of Texas (USA) seem to have found a different solution: they turned the service cells of the nervous system, astrocytes, into neurons.
Such attempts have been made for a long time. So, in 2008, experts from Stanford (USA) turned rat skin cells into neurons by putting them through a "stem-like" state, and in 2010 the same group managed to directly carry out this transformation using three or four proteins (a year later the same thing was done for human cells). Researchers from Ludwig–Maximilian University of Munich (Germany) in 2012 turned pericytes into brain neurons, which enter the blood-brain barrier in the blood vessels of the brain; a year later at Lund University (Sweden) this procedure was repeated for astrocytes in the brains of live mice.
But all this, it is easy to see, was done for brain cells, and the team of Chun-Li Zhang (Chun-Li Zhang) wanted to check whether it was possible to get neurons for the spinal cord brain in this way. The researchers chose astrocytes again because these service cells trigger the healing and scarring of nerve tissues after damage, protecting the surviving neurons, but at the same time inhibiting the growth of cells in the affected area.
Astrocytes regulate synaptic signal transmission in several ways. The axon transmits a nerve signal to the dendrite due to the release of a neurotransmitter (indicated in green) – in this case, glutamate. In addition, the axon releases ATP (yellow). These compounds cause calcium (violet) to move inside astrocytes, which encourages them to communicate with each other by releasing their own ATP. Astrocytes can enhance the transmission of a nerve signal by releasing the same neurotransmitter (glutamate) or weaken the signal by absorbing the neurotransmitter or releasing its binding proteins (blue). In addition, astrocytes can secrete signaling molecules (red) that will cause the axon to increase or decrease the release of the neurotransmitter when it resumes impulsing (Douglas Fields, "The Other part of the brain" – VM.With the help of modified viruses that delivered genes to astrocytes, scientists found out that a single SOX2 gene is enough to reprogram cells.
Astrocytes, having received SOX2, turned into neuroblasts, precursors of neurons. The method worked both in cell culture and in live mice with spinal cord injuries. Some of these neuroblasts turned into ordinary neurons, and the efficiency of the process could be doubled if the cells were additionally stimulated with valproic acid.
New neurons, as researchers write in Nature Communications (Zhida Su et al. In vivo conversion of astrocytes to neurons in the injured adult spinal cord), did not remain alone, but formed connections with motor neurons of the spinal cord.
The main pathos of the work is that new spinal neurons were obtained directly in a living organism, and here, of course, you can start fantasizing about the times when mobility will return to paralyzed people, and not thanks to super-technological prostheses, but with the help of such a transformation of some cells into others. The transformation here is indirect, the cells go through the stage of the precursors of neurons, but there is a plus in this: although the whole process takes longer than direct transformation, as a result, neuroblasts are obtained from one astrocyte, which can divide and give more than one neuron per one initial astrocyte.
However, there are a lot of questions to work with. Firstly, so far the method is not very effective: only 3-6% of astrocytes at the site of the introduction of the gene therapy vector can be turned into neuroblasts, and the resulting neurons are not enough not only for the animal to show some visible improvements, but also to check (with the help of electrodes) the functionality of new cells. In fact, the authors have so far managed to prove only that such an approach can be implemented in a living spinal cord.
Secondly, there is one paradox associated with the SOX2 gene used for transformation. According to Marius Wernig from Stanford (under his leadership in 2008 it was possible to turn skin cells into neurons), SOX2 is usually active in the precursors of neurons, but it is needed in order to prevent the transformation of a neuroblast into a neuron. Why, then, is it with its help that astrocytes turn into neurons? The authors of the work respond to this as follows: it's all about the degree of activity of the gene: depending on this, the cell either remains as it was, or begins to be reprogrammed. In general, you can't do without additional research here...
Prepared based on the materials of the Southwest Medical Center at the University of Texas:
Researchers generate new neurons in brains, spinal cords of living adult mammals.
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