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best for learning and memory ... mitosis and neuronal differentiation!

By: Lionel Perez Valenzuela

tissues repair themselves

Whenever we get hurt or suffer an injury, we observed that in the course of days the wound is closed and tissue repair. These mechanisms repair and generation of new cells to replace damaged or aged stem cells are essential.

undifferentiated stem cells, versatile and almost limitless ability to multiply are similar to embryonic cells. Not only can generate copies of themselves by mitosis, but by mitosis and differentiation can generate other cell types. While

tissues have some ability to repair itself, the brain seemed very limited in this regard. The adult brain can sometimes compensate for injuries suffered by establishing new connections between surviving neurons. But if the damage is too extensive this may not be enough. We must also differentiate

neuronal regeneration of neuronal replacement. When a neuron is cut the axon is regenerated, ie the cell tries to return to their previous structure. Neuronal replacement (neurogenesis) is a different concept is to produce new neurons.

But what thought is that neurons born only during the embryonic period and perhaps during the first two years of life a human being. From that moment, if you lost them, we could not replace them.

Why can not generate new neurons in the adult brain?

Neurobiology until recently argued that it was not possible because the adult brain was devoid of stem cells.

A dogma which falls ...

Argentine biologist Fernando Nottebohm of Rockefeller University, discovered that adult canaries can generate new neurons to replace other brain cells when you have to learn new songs or new sources of food recall or recognize new social companions.

words, when the brain needs to store new information and situations neurogenesis occurs, thus completing a dogma of neuroscience, arguing that generate new neurons in adult brains was impossible. It also established that brain stem cells (stem cells), were responsible for this process.

These investigations Fernando Nottebohm, then were extended and confirmed in different mammals, mice, monkeys and then humans. Therefore, our adult brains produce new neurons also fully functional. This fact, opens a whole new range of possibilities, and that wherever possible therapeutic replacement of neurons in human brains affected by injuries or neurodegenerative diseases, could repair the damaged brains of patients.

also means a whole change in the conception of the brain. It turns out that the brain is so different from other organs and tissues, where cells are constantly renewed from stem cells undifferentiated. The brain also undergoes this process of constant change and treble.

The hippocampus and memory

The hippocampus is a brain region, located in the medial temporal lobe. This curved structure reminiscent of a hippocampus. The hippocampus and adjacent structures perceptions become long-term memories.

While this region of the brain memory is stored, is essential for the formation of memories. In the hippocampus integrates information from other brain regions of alli'su importance and people with brain injuries in the temporal lobes can not form new memories but can remember events before the injury.






Basically the formation of new neurons in rats, monkeys and humans occurs in the hippocampus and the lateral ventricle. Specifically in the hippocampus in a layer of neurons called granule cells or granule neurons (see the first figure of the article). Undifferentiated stem cells do mitosis (proliferation), some die and others survive. Then some surviving cells migrate to the granule cell layer and differentiate to generate new functional neurons.






demonstrates how the proliferation of stem cells in the brain?

In 1965, Joseph Altman and Gopal D. Das of MIT (Massachusetts Institute of Technology) described the development of neurons in the hippocampus of adult rats, specifically in the dentate gyrus (gyrus dentatus). But the methods then available did not allow to estimate the number of neurons that formed, or to demonstrate that these new cells were neurons.

also was unknown concept of brain stem cells and mainstream science at that time required the replication of mature cells (already differentiated). These facts, together with lack of evidence of neurogenesis in monkeys were made Altman studies were underestimated.

This situation continued until the mid-eighties when the spectacular discoveries of Fernando Nottebohm, already mentioned, renewed interest in neurogenesis in the adult brain. The results in canaries were later confirmed in primates by teams of Elizabeth Gould, Bruce McEwen and Eberhard Fuchs. Techniques used

in primates based on DNA replication that occurs in the period S of the cell cycle. Before mitosis, cells replicate (duplicate) the amount of DNA they have to ensure that daughter cells receive a complete chromosome.

In these experiments animals are injected with a material (a nucleoside analogue of thymidine, bromodeoxyuridine the - BrdU - which is used as a marker, replacing thymidine), which integrates into the DNA, but only in cells that replicate their DNA in preparation for cell division. After BrdU antibody can be used to detect cells that incorporated it. As the marker material is integrated newly synthesized DNA, then goes on to be part of the DNA in the resulting daughter cells, which in turn can transmit it to the next cell progeny.

Some of the cells that incorporated BrdU differentiate into neurons or glial cells. The time necessary to differentiate the brain is removed, cut into sections, cuts and stained cells are identified by their anatomical and biochemical characteristics. They can identify cells with the marker (test cells from recent cell division) and which in turn have all the features of differentiated neurons. As the neurons differential can not enter the marker as it is not divide, cells must necessarily be differentiated into neurons after incorporating the marker.

Obviously this technique can not be performed in humans, which seemed an insurmountable obstacle until Peter Eriksson gave the Salk Institute with the solution. Eriksson found the same substance used as a marker BrdU also administered to some patients with cancer of the tongue or larynx terminals. These patients were encuadrdos in an experimental study and were injected with BrdU to control tumor growth. If the hippocampus could be obtained when patients died, could be identified if there neurogenesis in adult patients, analogous to studies in primates. Eriksson won the consent of patients and with their help were able to confirm neurogenesis in all cases.

The new neurons are also essential for learning.

Then the brain is constantly remodeling, there is not only synaptic plasticity (the ability to establish new connections), but a continuous generation of new neurons. The brain is permanently reshaped. Why

Why take the hard work of generating new neurons constantly?
Well apparently, as experiments in mice demonstrate this process is essential for learning and memory.

The crucial experiment, by Ryoichiro Kageyama of Kyoto University, consists of genetically modified mice subjected to an experiment in learning and memory.

These mice can not generate new neurons, so if your memory and learning depend on them, will have difficulties in memorizing and learning when compared with normal mice.

modified mice produce new neurons but by supplying a drug, new neurons produce a protein that kills. This ensures Kagemaya team that mice have no new neurons.

The researchers proceeded to measure how well the mice memorized the position of a concealed hole (a standard test to measure memory in mice). Mice usually takes a couple of days to remember the position of the hole and are able to remember more than a week.

Mice that new neurons can not take five or six days to learn where the hole and forget it completely within a week.

remains to be done

At some point, studies on the control of neurogenesis achieve a degree depth and maturity and should be replaced by Roederer studies in monkeys and then must expand research in humans. The protocols must be highly refined to show that the treatments did not affect normal brain capacity.

"The brain circuits are not written in stone," says Pankaj Sah of the Queensland Brain Institute. The brain is malleable and growing even in adults, and these studies in mice are the first to try the neurogenesis produces functional neurons essential for memory and learning.

Many older people, as they get older they lose this ability to produce new neurons in the hippocampus, perhaps that suffer memory loss. With the discovery of the potential of brain neurons to replace their own opens a whole new field of research in neurobiology and medicine, perhaps in the future may bring relief to people suffering from neurodegenerative diseases or serious injuries.