18 octubre 2014

El rol de la mielina en el aprendizaje motor

Es sabido que las sinapsis entre neuronas se fortalecen cuando se disparan los circuitos en los que se encuentran esas neuronas, y siempre se ha creído que este fortalecimiento sináptico, llamado potenciación a largo plazo, o LTP, es el sustento del aprendizaje. William Richardson cree que su estudio no contradice tal idea sino que le añade un refinamiento, y es que posiblemente esos circuitos deben cumplir la condición de estar mielinizados para sustentar el aprendizaje. 

 Myelin’s Role in Motor Learning
The production of new myelin in the brain—a function of non-neuronal glial cells—may be necessary for motor learning, a mouse study shows.
By | October 16, 2014

Oligodendrocytes extend thin processes of their cell membranes to form the myelin sheaths that wrap around neuronal axons.WIKIMEDIA, Changes in myelin, the fatty sheaths that insulate neuronal axons, may play a role in motor learning, according to a study published today (October 16) in Science. Genetically engineered mice that could not produce myelin were less skilled at learning a new motor task—running on a wheel with unevenly spaced rungs—than control mice.
“The paper shows very clearly that the ability to generate new myelin is necessary for adult mice to learn a complex motor task,” said the University of Michigan’s Gabriel Corfas, author of an accompanying commentary in Science and who was not involved in the research.
Moreover, because myelin is produced by non-neuronal glial cells called oligodendrocytes, which myelinate axons by extending thin processes of their cell membranes to wrap around them, the study challenges the long-standing assumption that learning results exclusively from changes to neuronal anatomy or function. “What this paper really does in a very compelling and elegant way is show that the glial cells . . . really perform much more important tasks than had hitherto been assigned to them,” said Robin Franklin, professor at the University of Cambridge, who studies the process of remyelination and who was not involved in the work. “This paper is a very significant step in a mounting body of work that shows that in fact the glial cells are not simply cells for neurons; they have, in their own right, fundamentally important roles in how the brain works.
“This is a very significant paradigm shift in the ways we think about how the brain changes in order to acquire information,” Corfas agreed.
Magnetic resonance imaging experiments in humans and rats have associated changes in the brain’s white matter, myelinated axons bundled together in large cables, with training in motor skills, but exactly how and why those changes were occurring was unclear. William Richardson, director of the Wolfson Institute for Biomedical Research at University College London, and his colleagues used a genetic system to selectively excise part of a gene called myelin regulatory factor (Myrf), inactivating it, in the oligodendrocyte precursor cells of laboratory mice. Myrf is not typically expressed in oligodendrocyte precursors but is necessary for the differentiation of new oligodendrocytes. “It’s not expressed until the precursors try and differentiate and express Myrf, and then if Myrf is missing, they just get stuck at that point,” said Richardson, “and we believe they die.” In other words, no Myrf means no new oligodendrocytes, and thus no new myelin. The system did not, however, affect preexisting oligodendrocytes.
Sure enough, mice lacking both copies of Myrf had fewer new oligodendrocytes and less myelin in the corpus callosum, a highly myelinated area that connects the two hemispheres of the brain and is involved in motor learning, compared with mice in which only one copy was deleted. Loss of Myrf also prevented mice from learning to run on a complex running wheel, with rungs unevenly spaced. Mice with both copies of Myrf quickly learned to use the new wheel and ran faster and farther per night than mice whose Myrf genes were inactivated.
To confirm that Myrf was impairing learning specifically, and not just motor skills in general, researchers tried introducing mice to the complex wheel before excising Myrf. In mice that had already learned to use the complex wheel, loss of Myrf had no effect on running speed, suggesting that myelin is important for learning but not recall or motor coordination.
“It’s known that the synapses between neurons strengthen when the circuits those neurons are a part of fire, and that has always been believed to be what underpins learning—this synaptic strengthening, so-called long-term potentiation,” said Richardson. “What our study shows is that although that undoubtedly does occur, there’s an additional refinement . . . which is that the active circuits presumably must get myelinated.”
Richardson added that he and his colleagues next plan to explore the roles of oligodendrocytes in other kinds of learning as well. “By finding a new mechanism involved in learning, it gives us a whole new target that in future we might be able to manipulate in order to, say, improve or accelerate learning,” said Richardson. Such information about the roles of myelination in learning could also be relevant to demyelinating diseases, such as multiple sclerosis, he added.
“I think this is an outstanding piece of work,” Franklin said. “It’s a landmark study in myelin biology and in neuroscience.”
I.A. McKenzie et al., “Motor skill learning requires active central myelination,” Science, doi: 10.1126/science.1254960, 2014.

17 octubre 2014

Descubren mecanismo de reparación del cerebro después de un accidente cerebrovascular

Mechanism that repairs brain after stroke discovered

October 10, 2014
Lund University
A previously unknown mechanism through which the brain produces new nerve cells after a stroke has been discovered by researchers. A stroke is caused by a blood clot blocking a blood vessel in the brain, which leads to an interruption of blood flow and therefore a shortage of oxygen. Many nerve cells die, resulting in motor, sensory and cognitive problems. The researchers have shown that following an induced stroke in mice, support cells, so-called astrocytes, start to form nerve cells in the injured part of the brain.

A stroke is caused by a blood clot blocking a blood vessel in the brain, which leads to an interruption of blood flow and therefore a shortage of oxygen. Many nerve cells die, resulting in motor, sensory and cognitive problems.
Credit: Image courtesy of Lund University
A previously unknown mechanism through which the brain produces new nerve cells after a stroke has been discovered at Lund University and Karolinska Institutet in Sweden. The findings have been published in the journal Science.
A stroke is caused by a blood clot blocking a blood vessel in the brain, which leads to an interruption of blood flow and therefore a shortage of oxygen. Many nerve cells die, resulting in motor, sensory and cognitive problems.
The researchers have shown that following an induced stroke in mice, support cells, so-called astrocytes, start to form nerve cells in the injured part of the brain. Using genetic methods to map the fate of the cells, the scientists could demonstrate that astrocytes in this area formed immature nerve cells, which then developed into mature nerve cells.
"This is the first time that astrocytes have been shown to have the capacity to start a process that leads to the generation of new nerve cells after a stroke," says Zaal Kokaia, Professor of Experimental Medical Research at Lund University.
The scientists could also identify the signalling mechanism that regulates the conversion of the astrocytes to nerve cells. In a healthy brain, this signalling mechanism is active and inhibits the conversion, and, consequently, the astrocytes do not generate nerve cells. Following a stroke, the signalling mechanism is suppressed and astrocytes can start the process of generating new cells.
"Interestingly, even when we blocked the signalling mechanism in mice not subjected to a stroke, the astrocytes formed new nerve cells," says Zaal Kokaia.
"This indicates that it is not only a stroke that can activate the latent process in astrocytes. Therefore, the mechanism is a potentially useful target for the production of new nerve cells, when replacing dead cells following other brain diseases or damage."
The new nerve cells were found to form specialized contacts with other cells. It remains to be shown whether the nerve cells are functional and to what extent they contribute to the spontaneous recovery that is observed in a majority of experimental animals and patients after a stroke.
A decade ago, Kokaia's and Lindvall's research group was the first to show that stroke leads to the formation of new nerve cells from the adult brain's own neural stem cells. The new findings further underscore that when the adult brain suffers a major blow such as a stroke, it makes a strong effort to repair itself using a variety of mechanisms.
The major advancement with the new study is that it demonstrates for the first time that self-repair in the adult brain involves astrocytes entering a process by which they change their identity to nerve cells.
"One of the major tasks now is to explore whether astrocytes are also converted to neurons in the human brain following damage or disease. Interestingly, it is known that in the healthy human brain, new nerve cells are formed in the striatum. The new data raise the possibility that some of these nerve cells derive from local astrocytes. If the new mechanism also operates in the human brain and can be potentiated, this could become of clinical importance not only for stroke patients, but also for replacing neurons which have died, thus restoring function in patients with other disorders such as Parkinson's disease and Huntington's disease," says Olle Lindvall, Senior Professor of Neurology.

Story Source:
The above story is based on materials provided by Lund University. Note: Materials may be edited for content and length.

Journal Reference:
  1. J. P. Magnusson, C. Goritz, J. Tatarishvili, D. O. Dias, E. M. K. Smith, O. Lindvall, Z. Kokaia, J. Frisen. A latent neurogenic program in astrocytes regulated by Notch signaling in the mouse. Science, 2014; 346 (6206): 237 DOI: 10.1126/science.346.6206.237

La joven china que probó que se puede vivir sin cerebelo

Escaner de la mujer sin cerebelo
  • 17 septiembre 2014. El cerebelo es una parte del cerebro fundamental para la vida humana, pero ¿es imprescindible? Hasta ahora se pensaba que sí, pero al parecer estábamos equivocados. Eso es por lo menos lo que demuestra el caso de una mujer china que se ha descubierto que no tiene cerebelo.
Los médicos hicieron el hallazgo después de la joven se sometió a pruebas a consecuencia de los vómitos y mareos que venía sufriendo desde hacía tiempo.El cerebelo regula la motricidad y está relacionado con el aprendizaje, las capacidades de la cognición, la atención y hasta el lenguaje. Por lo tanto se supone que una persona con daños en este órgano tendría serias dificultades a la hora de andar y hablar por ejemplo.En el caso de la mujer china, aunque no logró caminar sola hasta los siete años y su habla no fue coherente hasta los seis, apenas ha sufrido transtornos asociados a la ausencia de cerebelo. Además, al alcanzar los 24 años se ha convertido en madre.El caso ha sorprendió a la comunidad médica.Según la publicación Brain gran parte de los pacientes en que se ha constatado esta anomalía son niños que, debido a dicha alteración, en ningún caso han llegado a alcanzar la edad adulta.

¿Cómo es posible vivir tanto tiempo sin cerebelo?

Normalmente las personas con daños en esta zona se debilitan mucho en sus habilidades motoras.
No obstante, el caso de esta joven provocó en ella apenas problemas leves tanto en sus movimientos como su capacidad para hablar. ¿Cómo es posible esto?
"Este caso ilustra que los circuitos cerebrales son aún más flexibles de lo que pensábamos. A pesar del hecho de que el cerebelo es la estructura del cerebro que contiene la mayor cantidad de neuronas, el cerebro en su conjunto puede trabajar sin él, con relativamente pocos síntomas", dijo a BBC Mundo el neurólogo Mario Manto, de la Universidad Libre de Bruselas (ULB).
Según Manto, demuestra "cómo el sistema cerebral funciona compensando las partes que faltan", sobre todo ante determinadas anormalidades que pueden presentarse desde el nacimiento.
En opinión de expertos, es muy probable que esta capacidad disminuya con la edad.
Aunque este no es el primer caso que se registra de una persona que nace sin cerebelo, los anteriores se referían a niños y bebés que mostraban deterioro mental severo, epilepsia y otros problemas estructurales del cerebro que los llevaron a la muerte generalmente.
Manto dijo que es "se necesita investigar más para establecer las causas que provocan este trastorno raro".