Mammalian Cerebellum Makes New Neurons

Neurogenesis breaks into the most static brain region Wednesday, 04 June 2008 Fifteen years ago, the discovery of adult neurogenesis (the production of new neurons) in the highly static, non-renewable mammalian brain was a breakthrough in neuroscience. Most emphasis was put on the possibility to figure out new strategies for brain repair against the threat of neurodegenerative diseases. Yet, unlike lower vertebrates, which are characterized by widespread postnatal neurogenesis, neurogenic sites in mammals are highly restricted within two very small regions. Hence, the fact that protracted neurogenesis in mammals is an exception rather than the rule slows down hopes for generalized brain repair. Work carried out in the recent past at the University of Turin, involving Paolo Peretto at the Department of Animal Biology, and Giovanna Ponti and Luca Bonfanti at the Department of Veterinary Morphophysiology, revealed striking examples of structural plasticity and neurogenesis in the nervous system of rabbits. These Lagomorphs show remarkable differences under the profile of neurogenesis with respect to their close relatives Rodents (mice and rats). Now, in a work published in this week's issue of PLoS ONE and coordinated by senior author Luca Bonfanti, new neuronal progenitors were found to be produced in the cerebellum of young and adult rabbits. This is rather astonishing since the mammalian cerebellum is known as one of the most static brain regions, wherein microscopic synaptic remodelling has long been considered as the only type of plasticity. In addition, unlike the two 'classic' neurogenic sites, the 'alternative' neurogenic sites discovered in rabbits are not remnants of embryonic germinal layers. These new cells are produced from neural progenitors localized within the mature brain parenchyma, thus representing a more widespread source of neurons and glial cells. This fact supports the emerging hypothesis that the existence of actively dividing parenchymal cell progenitors could be more interesting than stem cells located in neurogenic sites, at least for future perspectives of brain repair. Under the functional profile, the unusual neurogenesis observed in rabbits could be related to a relatively longer lifespan of these animals, if compared to the short lived Rodents. This hypothesis opens new fields of research in humans, wherein adult neurogenic sites are known to exist, but less it is known about other regions of their large-sized brain. Reference: Genesis of Neuronal and Glial Progenitors in the Cerebellar Cortex of Peripuberal and Adult Rabbits Giovanna Ponti, Paolo Peretto, Luca Bonfanti PLoS ONE 3(6): e2366. doi:10.1371/journal.pone.0002366 ......... ZenMaster

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Finding Clues for Nerve Cell Repair

Finding Clues for Nerve Cell Repair Tuesday, 03 June 2008 A new study at the Montreal Neurological Institute at McGill University identifies a key mechanism for the normal development of motor nerve cells (motor neurons) - cells that control muscles. This finding is crucial to understanding and treating a range of conditions involving nerve cell loss or damage, from spinal cord injury to neurodegenerative diseases such as ALS, also known as Lou Gehrig's disease. Nerve cell regeneration is a complex process. Not only do nerve cells have to regenerate, but just as importantly, their specific and individual connections need to be regenerated also. The study, published recently in the Proceedings of the National Academy of Sciences, provides invaluable insight into these vital processes by understanding the mechanisms involved in normal development of selected types of spinal cord motor nerve cells. Motor neurons are highly specialized. They have distinct characteristics and connect to specific muscle types in specific regions of the body. "These highly targeted nerve cell-to-muscle connections are determined in part by specific patterns of gene expression during embryonic development. More specifically, certain genes are expressed which tell the neuron what its properties will be, where to settle and which particular muscle to connect with," says Dr. Stefano Stifani, neuroscientist at the Montreal Neurological Institute and lead investigator in the study. When nerve cells develop they require characteristic patterns of gene expression in order to become motor neurons or another type of nerve cell called interneurons. Dr. Stifani and colleagues show that during development, motor nerve cells have to express certain genes that continually suppress interneuron developmental characteristics. "We have identified a key factor, called Runx1, which controls the correct development of motor neurons in the upper part of the spinal cord. Runx1, a factor that controls gene expression, helps motor neurons to maintain their status by regulating the expression of specific genes. In doing so, it might also help motor neurons find their target muscles." Understanding the normal development and the highly specialized nature of nerve cells has important implications for understanding diseased or damaged nerve cells. For example, in ALS, the motor nerve cells that are involved in swallowing and controlling the tongue are often the first to degenerate. Knowing the specific patterns of gene expression of different motor nerve cells may help to explain why certain motor neurons are more susceptible to degeneration and help identify new targets for treatments. Reference: Suppression of interneuron programs and maintenance of selected spinal motor neuron fates by the transcription factor AML1/Runx1 Nicolas Stifani, Adriana R. O. Freitas, Anna Liakhovitskaia, Alexander Medvinsky, Artur Kania , and Stefano Stifani PNAS April 29, 2008, vol. 105, no. 17, 6451-6456 ......... ZenMaster

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'Cyborg Engineering' for Coronary Bypass Grafting

Study reports success at combining man-made materials with human cells Tuesday, 03 June 2008 A team of London scientists have taken a major step in making the use of artificial veins and arteries in coronary bypass grafts a reality. In a study published in the June 2008 print issue of The FASEB Journal, researchers describe how they developed this artificial graft tissue by combining man-made materials with human cells to make it elastic and durable and so it can attach to host tissue. "Obviously this advance could be a medical breakthrough that saves millions of lives around the world," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal, "but even more tantalizing is the successful fusing of living cells to nonliving substances that actually — heal — by forming a stronger bond to each other and to host tissue once put in use. This might even be called a start toward 'cyborg engineering.'" In the research report, scientists describe how they took an elastic scaffold (the material that gives the artificial graft its shape) of compliant poly(carbonate-urea)urethane and incorporated human vascular smooth muscle cells and epithelial cells from umbilical cords. Then they took the artificial grafts and simulated blood flow in the laboratory to test their durability. They found that as the pulsing fluid flow slowly increased, the artificial graft's performance actually improved. The researchers hypothesize that this improvement is because the movement of fluid through the graft stimulates the smooth muscle and epithelial cells to release proteins that strengthen their ability to attachment to the elastic scaffold and other tissues. "The notion that any body part could be engineered in a lab, attach to existing tissue 'naturally,' and grow stronger as it is being used is something thought completely impossible just 20 years ago," Weissmann added. "It is only a matter of time before human tissues can be engineered to be at least as good as the originals, and this study moves us toward that reality." According to the National Institutes of Health, coronary artery bypass grafting is the most common open heart surgery in the United States, with 500,000 procedures performed each year. It is one of only a few surgical options to treat coronary artery disease, which is the leading cause of death in the United States. During this surgery, a healthy vein or artery from another part of the body is connected to the blocked coronary artery to route blood flow around a blocked passage. Current procedures are limited, however, by the availability of healthy veins or arteries as well as the patient's ability to survive both aspects of the procedure. Furthermore, many patients experience significant pain in the area where the vein or artery was removed. Using artificial veins or arteries instead would reduce recovery time, reduce pain, and save lives by making this type of surgery more available to people who need it. Reference: Tissue engineering of a hybrid bypass graft for coronary and lower limb bypass surgery S. T. Rashid, B. Fuller, G. Hamilton, and A. M. Seifalian FASEB J. 2008 22: 2084-2089 ......... ZenMaster

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