The neuron lived, the neuron is alive, the neuron will live!
Embryonic neuron transplantation gives hope
for effective treatment of brain diseases
LifeSciencesToday based on materials from the University of California, San Francisco:
Transplantation of Embryonic Neurons Raises Hope for Treating Brain DiseasesUCSF scientists' Experiments Challenge the dominant theory of cell death in the developing brain
The increased survival ability of embryonic neurons transplanted into the brains of newborn mice, unexpected for neurologists, established in a series of experiments conducted at the University of California, San Francisco (UCSF), gives hope for the effective use of nerve cell transplantation for the treatment of diseases such as epilepsy, Alzheimer's, Huntington's, Parkinson's and schizophrenia.
The experiments described in an article in the journal Nature (Southwell et al., Intrinsically determined cell death of developing cortical interneurons) were not intended to test the effectiveness of embryonic neuron transplantation as a treatment method for any particular disease. But they provide evidence of the correctness of the concept, that is, the possibility of transplantation into the brain of significant amounts of GABA-ergic interneurons – a type of brain cells associated with various neurodegenerative and other neurological diseases. The fact established by scientists is also important that such transplantation does not have a negative impact on the population of endogenous interneurons.
The higher-than-expected survival rate of transplanted embryonic interneurons came as a big surprise to the researchers.
According to the most common theory, the survival of developing neurons is something like playing chairs with music. In the brain, these cells are allocated a limited space, which forces them to compete with each other. Only those who manage to "take a place" in time (and get the signals necessary for survival from other cell types) survive until the music stops. The prospect of other neurons is bleak – they will simply wither away.
Based on this theory, scientists assumed that, regardless of the number of transplanted embryonic interneurons, only a certain, and small, number of transplanted cells would survive in the brains of adult mice. But what they observed was radically different from what was expected: regardless of the number of transplanted cells, a certain percentage of them always survived.
"[Such a constant survival rate] suggests that these cells, which, as other studies have shown, are very promising from the point of view of therapy, can be added to the cortex in significant quantities," comments the results of the study, its leader Arturo Alvarez–Buylla, PhD, professor of neurosurgery, researcher at the Center. Regenerative Medicine and Stem Cell Research by Eli and Edythe Broad (Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research) UCSF.
Past work by UCSF scientists and other research centers has shown that interneurone transplantation can reduce the number of seizures in animals with models of epilepsy, as well as correct motor disorders similar to those observed in Parkinson's disease in laboratory rats. The functions of these cells are often disrupted in Alzheimer's disease, and their number is changed in the brain of patients with schizophrenia. When transplanted into the spinal cord, embryonic interneurons largely suppress pain.
In the current study, UCSF scientists found that when the number of transplanted cells changes, their constant proportion rather than a constant number survives, which means that some part of the cells are "sentenced" to death by autonomous cellular mechanisms or that the survival factor is secreted by the inhibitory neurons themselves. In addition, experiments have shown that interneurons can be transplanted in much larger quantities than previously thought – an observation of great importance for using these cells to adjust the balance between the processes of excitation and inhibition in the diseased brain.
The survival of neurons is determined by unknown factorsGABA-ergic interneurons perform an important function – they balance the action of excitatory neurons in the cerebral cortex by synthesizing and secreting inhibitory chemical signals.
Diseases such as epilepsy, Alzheimer's, Huntington's, Parkinson's, and schizophrenia are somehow associated with disturbances in the balance of excitation/inhibition, and problems with gabaergic interneurons are characteristic of all these ailments.
GABAERGIC interneurons are not formed in the cortex, the area of the brain in which they will eventually be included in the functional circuits. These neurons are "born" in a distant part of the developing brain from the cortex, and then migrate to their destination. For decades, scientists have been searching for an answer to the question of what determines the appropriate number of these cells, how many of them are formed when they die and how many of those that have reached the cortex survive in the end. Some of these unknowns have been considered in this publication, but it describes one unexpected observation.
It is believed that the number of neurons is determined by the presence of survival signals produced by certain target cells. This idea, known as the "neurotrophic hypothesis", is based on experiments conducted in the 1940s, which brought their authors the Nobel Prize and showed how the survival of developing neurons in the spinal cord and peripheral nervous system is determined. It followed from this work that only those nerve fibers survive that were able to correctly establish a connection with targets outside the nervous system, and that these targets synthesize a protein – nerve growth factor – responsible for the survival of nerve fibers.
The neurotrophic hypothesis defines ideas about how and why brain cells live and die for many years.
"Since then, it has been believed that the neurotrophic hypothesis applies to all types of neurons and to all areas of the nervous system," explains the first author of the article, Derek Southwell, MD, PhD.
It was assumed that, after gabaergic interneurons have made their way to the right part of the brain, only those of them that have merged with other neurons already there and are protected by some protein or other factor remain alive. However, the survival of transplanted interneurons does not depend on competition for survival signals synthesized by other types of recipient brain cells.
While the new experiments do not refute this theory in terms of how nerves outside the brain form connections with their targets, they suggest that gabaergic neurons may also experience the action of some other, as yet unknown, mechanism.
Portal "Eternal youth" http://vechnayamolodost.ru23.10.2012