09 June 2014

Neurons tell stem cells that new neurons are needed

The first link of a new brain recovery chain has been found

LifeSciencesToday based on Duke University Materials: Neuron Tells Stem Cells to Grow New NeuronsScientists from Duke University have discovered a new type of neurons in the brain of an adult organism.

These neurons are able to transmit information to neural stem cells about the need to start actively differentiating into neurons. Although the experiments are at an early stage, their results suggest a possible ability of the brain to self-repair.

Some time ago, neuroscientists suspected that the brain has a certain ability to control the formation of new neurons, but it was difficult to determine where these instructions come from, explains study leader Chay Kuo, MD, PhD, associate professor of cell biology, neurobiology and pediatrics.

In a study on mice, his group found a previously unknown population of neurons in the subventricular zone (SVZ), a neurogenic niche of the adult brain adjacent to the striatum. These neurons synthesize choline acetyltransferase (ChAT)– an enzyme necessary for the synthesis of the neurotransmitter acetylcholine. Using optogenetic tools that made it possible to adjust the frequency of ChAT+ neurons firing using a laser, the researchers were able to see clear changes in the proliferation of neural stem cells.


In the sub-perpendicular neurogenic niche of the adult brain, electrical signals,
generated by ChAT+ neurons, give rise to new migrating neuroblasts,
visible in the drawing moving through the cells of the ependyma.
(Fig. O'Reilly Science Art)

An article with the results of these experiments was published on June 1 in the early online edition of the journal Nature Neuroscience (Paez-Gonzalez et al., Identification of distinct ChAT neurons and activity-dependent control of postnatal SVZ neurogenesis).

The population of mature ChAT+ neurons is only one part of an undescribed neural circuit that apparently interacts with stem cells and informs them of the need to strengthen the formation of new neurons, explains Dr. Kuo. Scientists do not yet know all the parts of this chain, nor the code it uses, but by controlling the signals of ChAT+ neurons, Dr. Kuo and his colleagues came to the unequivocal conclusion that these cells are necessary and sufficient to control the formation of new neurons in the SVZ niche.

"We were studying how neurogenesis is maintained in the brain of an adult organism. And it was very unexpected and interesting to discover this hidden pathway – a neural circuit that directly controls the formation of immature neurons by stem cells," Dr. Kuo continues. "It was an exciting treasure hunt, during which we repeatedly found ourselves at a dead end!".

This project was initiated more than five years ago when, while studying how the SVZ niche is formed, the lead author of an article in Nature Neuroscience, Patricia Paez-Gonzalez, encountered neuronal processes associated with neural stem cells.

The young neurons formed due to these signals were intended for the olfactory bulb of mice, since in rodents a significant part of the brain is associated with the sense of smell and needs new neurons to support this process. But it is possible that in humans, with its much less pronounced olfactory bulb, new neurons are formed for other areas of the brain. One of these areas may be the striatum.

When studying post-stroke lesions in rodents, it was noticed that SVZ cells apparently migrate to the neighboring striatum. And just last month, in the journal Cell, a group of Swedish scientists reported that for the first time they observed newly formed neurons – the so–called interneurons - in the human striatum. Swedish researchers also reported another interesting fact: in patients with Huntington's disease in this area, newborn interneurons appear to be absent.

According to Sally Temple, director of the Rensselaer Neural Stem Cell Institute, who did not participate in this study, "this is a very important and significant cell population that controls stem cells. To understand how innervation comes into play in the subventricular zone is really very interesting."

Dr. Kuo's group discovered this system by following cholinergic signaling, but other scientists have come to the same niche on dopaminergic and serotonergic signals, continues Temple. "It's really a very hot area because it's an excellent niche for stem cell research. It is in this magnificent niche that intercellular interactions can be observed."

The rediscovery of cellular connections gives Dr. Kuo hope that scientists will eventually be able to find a way to "attract certain circuits of the brain to update its hardware." "How wonderful it would be if we could modernize the hardware of the brain so that it could be at the level of new software." According to him, there may be a way to combine behavioral therapy and stem cell treatment after a brain injury in order to eliminate at least some of the damage.

The questions that Kuo and his colleagues are now facing are what are the signals above and below with respect to ChAT+ neurons. What brain signals addressed to ChAT+ neurons cause them to transmit information to stem cells about the need to generate young neurons, and what is the logic that controls the response of stem cells to different frequencies of ChAT+ electrical activity?

The big question is also how new components are introduced into an already existing neural circuit – a practice that the brain usually resists using.

"I think some neural circuits accept new members, and some don't," Dr. Kuo suggests.

Portal "Eternal youth" http://vechnayamolodost.ru09.06.2014

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