Neurons can be reprogrammed long after they’ve matured

Laura

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See: http://www.rawstory.com/rs/2013/02/26/neurons-can-be-reprogrammed-long-after-theyve-matured-study-finds/

and: http://neurophilosophy.wordpress.com/2006/08/29/the-discovery-of-the-neuron/

Several years ago, Caroline Rouaux and Paola Arlotta of the Harvard Stem Cell Institute identified Fezf2 as the master gene which activates the genetic program that causes the immature cells in cortical layers 2/3 to differentiate into large, pyramid-shaped neurons that project axons to the opposite side of the brain to form the corpus callosum, a massive bundle of approximately 100 million fibres connecting the two hemispheres.

In their new study, the researchers fused Fezf2 to the gene encoding green fluorescent protein and to a genetic switch that activates both genes, but only in migrating neurons destined for layers 2/3. They injected this recombined DNA into the brains of embryonic mice at about halfway through their 28-day gestation period, and then applied a weak electrical field across the embryos’ heads, which induces transient pores in nerve cell membranes so the DNA can enter.

Rouaux and Arlotta examined the animals’ brains under the microscope after four days, at birth, and up to one month of age. In all cases, they found green fluorescent cells not only in layers 2/3, but also in deeper layers. What’s more, the axons from some of the cells extended not to the other side of the brain, but downwards, and expressed genes that are normally active only in layer 5/6 cells. Some had extended into a sub-cortical structure called the thalamus, and others reached the spinal cord. The reprogrammed cells remained stable for at least a month, and further experiments revealed that the capacity for reprogramming persisted until three days of age, but had been eliminated by three weeks of age.

Nevertheless, the findings show that neurons can be reprogrammed long after they differentiated and matured. Researchers have made huge advances in reprogramming cells taken from various parts of the body, but until now it was unknown whether this could also be done in the living body. Although the cells lost the capacity to switch identity when the animals were just three days of age, it may be possible to extend the period of reprogramming to the mature brain.

Layer 5/6 form a pathway called the corticospinal tract, which projects down into the spinal cord and forms connections with motor neurons in the spinal cord, and these in turn connect to muscle cells. The corticospinal tract is essential for voluntary movement, and its cells are damaged in stroke, motor neuron disease and spinal cord injury and various other conditions. The new findings could eventually lead to gene therapies which reprogram cells in the patient’s brain to generate new corticospinal neurons.

Reference: Rouaux, C. & Arlotta, P. (2013). Direct lineage reprogramming of post-mitotic callosal neurons into corticofugal neurons in vivo. Nat. Cell Biol. doi: 10.1038/ncb2660
 
Reading the above makes me wonder if proper dietary changes combined with resistance activity and a little electrical help, say from comet or meteorite atmospheric entry, could enable these neurons to be reprogrammed en masse globally instead of in a controlled lab setting. Since humans are not mice, one also wonders what the limit would be, if any, for reprogramming neurons. It will be interesting to see further research done on this subject to see how far the reprogramming goes.

I also wonder if the above scenario were initiated in humans if other types of regeneration would manifest, possibly reversing many other injuries or effects of illnesses. In the experiment they do not state how long the electrical field was applied to the heads of the mice, so I would think the length of exposure to an electrical field would be a mitigating factor.

I attempted to access to paper but it either requires a subscription or must be purchased individually. Is this paper important enough to warrant purchasing it so excerpts can be posted here? If so, I am willing to get it so those who have a far greater understanding of biology than I do may have a chance to read the full text. I myself find the experiment fascinating considering the small amount that was published in the link that was provided.
 
QuantumLogic said:
Reading the above makes me wonder if proper dietary changes combined with resistance activity and a little electrical help, say from comet or meteorite atmospheric entry, could enable these neurons to be reprogrammed en masse globally instead of in a controlled lab setting. Since humans are not mice, one also wonders what the limit would be, if any, for reprogramming neurons. It will be interesting to see further research done on this subject to see how far the reprogramming goes.

I had the same thoughts. Perhaps those of us following certain lifestyle choices will react differently to others? There seems to be no limit to the possibilities :)


I attempted to access to paper but it either requires a subscription or must be purchased individually. Is this paper important enough to warrant purchasing it so excerpts can be posted here? If so, I am willing to get it so those who have a far greater understanding of biology than I do may have a chance to read the full text. I myself find the experiment fascinating considering the small amount that was published in the link that was provided.


I believe the paper is available here:
_http://www.readcube.com/articles/10.1038/ncb2660
 
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