Glue for axons
The protein responsible for spinal cord recovery after injury has been found
Oleg Lischuk, N+1
American and German scientists have discovered in the danio-rerio fish a molecular mechanism responsible for restoring the spinal cord after injury. The results of the work are published in the journal Science (Mokalled et al., Injury-induced ctgfa directs glial bridging and spinal cord regeneration in zebrafish), and related editorial material is also devoted to them.
In mammals, spinal cord injury leads to the formation of a scar from glia (auxiliary cells of the nervous system), other cells and extracellular matrix. The axons of neurons are interrupted in this case, and signals from the brain are not carried below the injury site. In lower organisms, such as zebrafish or newts, glial and other cells proliferate, migrate and differentiate in response to spinal cord rupture, forming a kind of bridge between the edges of the injury. This bridge contributes to the restoration of axons and, as a result, the functions of the spinal cord. What molecular mechanisms regulate such a cellular reaction has not been known until now.
Cellular bridge at the site of spinal cord injury danio-rerio
To find out, researchers at Duke University and the Max Planck Institute for Heart and Lung Research surgically dissected the spinal cord of the danio-rerio and screened the transcriptome in search of genes whose expression increases in response to damage.
It turned out that CTGFa (connective tissue growth factor a), a multifunctional cytokine, plays a key role in the formation of the cell bridge and subsequent regeneration of axons, affecting various signaling pathways regulating the processes of adhesion, migration, proliferation and differentiation of cells, the formation and remodeling of blood vessels, bones and connective tissue, including in response to damage.
To clarify the effects of CTGFa, scientists obtained a transgenic danio-rerio with the gene of this protein turned off. In such fish, the formation of a cellular bridge, the growth of axons and the restoration of functions after spinal cord injury were disrupted. On the contrary, an increase in CTGFa expression stimulated these processes. The same effect was observed when recombinant human CTGF was injected (mammals, unlike zebrafish, do not have isoforms a and b of this protein) into the site of nerve tissue damage.
Formation of a cell bridge in the presence, absence and excess of CTGFa
(drawing from an article in Science)
An increase in CTGFa expression in response to spinal tissue injury in danio-rerio is observed for about three weeks, which correlates with the duration of cell bridge formation. In mammals, in particular rats, spinal cord injury causes a longer production of CTGF, which may be due to excessive growth of scar tissue that does not allow axon growth.
The obtained results show that CTGFa is necessary and sufficient for the formation of a glial bridge and natural regeneration of the spinal cord, the authors write. In addition, they provide a direction for research on the restoration of the spinal cord in mammals, which in the future may lead to the development of effective methods for treating its injuries.
Earlier, scientists figured out the regulation of the last stage of regeneration of the spinal cord of the zebrafish - the growth of damaged axons. It turned out that it is responsible for the stimulation of serotonin 5-HT1A receptors.
A small recovery of functions after spinal cord injury has recently been achieved in humans with the help of virtual reality, a neurointerface and a robotic exoskeleton.
A group of scientists planning to perform a human head transplant has achieved some success in the regeneration of the spinal cord in animals. They treated the sections with polyethylene glycol (including graphene nanofilms) and performed electrical stimulation of nerve fibers. However, many experts found these publications insufficiently convincing.
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10.11.2016