Currently viewing the category: "Neurons & Genes"

Stained motor neuron from human spinal cord; Courtesy Wikimedia Commons.

Historically, the medical approach to curing the incurable effects of tragic spinal cord injuries–such as the case made famous by America’s classic super hero, Christopher Reeve–has been to affect regeneration of damaged nerves through stem cell therapy or by introducing growth factor proteins, like BDNF. Success with these applications has yet to be realized, as apparently the adult body’s resistance to re-growing its nerve centers is stronger than expected.

Recently, however, a team at Children’s Hospital Boston lead by Zhigang He, has been developing an alternate approach to the problem. Instead of trying to force existing nerve fibers to regrow, or by introducing new cells to take their place, the group manipulates the communication in the cells to “turn off” an apparent gene that tells the neuron to stop growing. With the gene shut down, then neuron is free to generate and flourish as it sees fit.

They have found at least three proteins involved with the critical myelin coating of neuronal axons, which actively work together to inhibit myelin growth. Blocking the proteins either genetically or chemically is being shown to promote the sprouting and re-generation of local structures in neuron networks.

The process is being tested in mice with spinal cord injuries by removing a special enzyme, called PTEN, that is activated in mature systems to limit cell growth. With the enzyme out of the picture, the cells think they are young again, and start to grow. No controversial stems cells, and no introduction of unnatural chemicals… just removing a little key that is in the way. Of course, it would likely be important to be able to replace the key once the damaged cells have rejuvenated, otherwise a cancer-like state might be a drastic side effect.

Although this new therapy is not near to human trials, it is a wonderfully positive example of how significant advances in human improvement might come from looking at problems at a little different angle. These experimental mice are just paving the way for the coming acceleration into reversing such devastating human experiences that include wide-spread nervous system damage and degradation.

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“Mice regain movement after spinal cord injury” :: Scientific American Observations :: August 8, 2010 :: [ READ ]

“PTEN deletion enhances the regenerative ability of adult corticospinal neurons”, Kai Lui, et al., Nature Neuroscience, August 8, 2010 [ READ full article :: Download PDF ]

“Spinal cord regeneration success in mice” :: BBC News Health :: August 8, 2010 [ READ ]

 

Polycaprolactone Microtubes, from PhysOrg.com

When peripheral nerves are damaged or even severed due to injury or disease, then dramatic disabilities can result in the affected individual. This may range from local paralysis of senses to the painful disorder ofneuropathy.

Neurons that loose their primary connections to one another through the axon–the main nerve fiber that transports electrical signals from the cell body to other neurons–are very slow to re-grow, and will likely die due to inactivity. If they do re-develop and connect, then the nervous system can re-learn how to have a reasonably-functioning network, but full recovery to its original condition is difficult.

To encourage and guide this re-growth process, a European collaboration of researchers are developing a new neurotechnology based on fabricated polymer microtubes that can be implanted and monitored during axon regeneration. Centered at the University of Glasgow’s Centre for Cell Engineering and Department of Electronics and Electrical Engineering under Dr. Mathis Riehle, the team plans to surgically insert these specialized tubes between two neurons whose axon fibers are severed. With a little electrical stimulation along the tube, they anticipate that the fibers will begin to grow along the length of the tube and establish a new neural connection on the other side… the neuronal equivalent of the “light at the end of the tunnel.”

The successful development of this technique will certainly mean significant improvements in recovery for patients with peripheral nerve damage. It may also pave the way for a more focused neuroengineering method for creating new connections in the human nervous system, and even helping living nerves functionally connect to implanted devices. Controlling the development and re-development of neuron networks will become a major leap for future neurotechnological advances.

“Scientists hope tiny tubes can help repair damaged nerves” :: PhysOrg.com :: August 16, 2009 :: [ READ ]

 

Flap its wing in the Brazilian rainforest, trigger a hurricane in the Gulf of Mexico…

This is the classic example of how small perturbations in a complex system poised near chaos can have dramatic effects throughout the entire system. The brain is certainly a complex system, although still minimally understood, so discovering physical evidence of the theoretical characteristics of complex systems is quite exciting.

Researchers from the Howard Hughes Medical Institute lead by Yang Dan of the University of California, Berkeley have presented evidence of a complex system in an anesthetized rat brain. They tried to stimulate a single cortical brain cell and then monitor the change in global neuronal activity elsewhere in the brain.

And global change there was. Each neuron can have thousands of interconnections, so the structural network is amazingly complicated. However, the system can be resting in a state that if the network activity just crosses a certain threshold, then the entire system can undergo what might be compared to a phase transition. And the hurricane can begin to form in the brain.

“A Single Neuron Can Change the Activity of the Whole Brain” :: PhysOrg.com :: May 1, 2009 :: [ READ ]

 

The absolute key to ultimately understanding how the brain works is developing a complete structural map of the neuron network and relating this structure to the overall network function.

As a comparison for example only, the Internet continues to develop as a complex network, but it still does not compare to the immensity of the lump of cells in our head. The structure of the neuron network directly leads to the resulting functionality of the human brain.

A wonderful visualization of a single neuron buried deep inside a network was created by the Blue Brain Project group from the Ecole Polytechnique Federale de Lausanne in Switzerland. Reflect for a while with the animation presented below, and then learn more about EPFL with their feature video presentation.

Link to Video

 

Neuron communication is not a trivial language and it has yet to be fully understood. This so-called “neural code” is certainly not as simple as a single electrical impulse each time a brain cell wants to say “Hi!” to a neighbor. There can be continuous signals, of varying strengths, and with the latest research from Prof. Anthony Zador at Cold Spring Harbor Laboratoryvarying timings.

Understanding how neurons communicate is fundamental to developing neuron-based technologies that will embed and integrate living neural devices into the human system. Of significant importance is the physical structure of the neuron network and how its patterning results in the overall network’s function. But, at a more basic level, it is being realized that the electrical signaling patterns between individual neurons is potentially even more complex with amplitude (signal strength), frequency, and even small-scale variations in frequency all being a critical component in the language… which ultimately guides the behavior of the neuron network and the organism.

“Experiments support alternative theory of information processing in the cortex” :: PhysOrg.org :: October 16, 2008 :: [ READ ]

“Millisecond-scale differences in neural activity in auditory cortex can drive decisions” :: Nature Neuroscience Brief Communication :: October 12, 2008 :: [ READ ]

 

How neurons develop their vast networks of axons and dendrites with apparently accurate targeting to generate a functioning brain remains a core question in neuroscience. Although some of the interconnections might be partially “random” with the resulting complex network still managing to generate meaningful neural function, it still seems that the network connects in a directed way. How neurons know with whom to connect remains mostly unclear.


Image from Salk Institute for Biological Studies

Using genetically-modified neurons from a mouse, the O’Leary research group from the Salk Institute for Biological Studies found a surprising additional function of a well-known protein called “p75.” Also involved in the regulation of keeping a neuron alive, it has now been observed to affect and direct axon growth.

And the function is rather interesting: the protein apparently does not act to attract an axon to follow a certain path… (“come follow me to the promised land!”), but rather it repulses the growth cone to head in another direction… (“yer git on outta here!”).

The important aspect of this research is leading to a complete understanding of neuron network growth and development, in particular the understanding of what controls how and where the network connections develop. If we know what are the biological controls, then we can in turn control or influence these factors to guide neurons implanted on a neurotechnological device to connect in specific ways that might be needed for a particular application.

Read more about this interesting work, and think about how this p75 protein might be involved in your next neurotech implant…

“A second career for a growth factor receptor: keeping nerve axons on target” :: Salk Institute Press Release :: September 11, 2008 :: [ READ ]