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   Biological fat with a sugar attached essential to maintaining brain's supply   
   of stem cells   
      
   Date:   
   November 3, 2014   
   Source:   
   Medical College of Georgia at Georgia Regents University   
      
   Dr. Robert Yu, MCG neuroscientist and corresponding author of the study in The   
   Journal of Neuroscience and Dr. Jing Wang, MCG postdoctoral fellow and the   
   study's first author.   
   Credit: Phil Jones   
   Fat and sugar aren't usually considered healthy staples, but scientists have   
   found that a biological fat with a sugar attached is essential for maintaining   
   the brain's store of stem cells.   
   Neural stem cells help the brain develop initially, then repopulate brain   
   cells lost to usual cell turnover as well as to a trauma or malady, such as a   
   head injury or stroke.   
   While the cell population and activity decrease as a natural part of aging,   
   scientists at the Medical College of Georgia at Georgia Regents University are   
   studying how neural stem cells are normally maintained with the long-term goal   
   of helping the    
   supply stay robust despite aging as well as infirmity.   
   They have discovered that in mice missing the sugar containing lipid   
   ganglioside GD3, neural stem cells have a dramatically impaired ability to   
   self-renew, said Dr. Robert K. Yu, MCG neuroscientist and corresponding author   
   of the study in The Journal of    
   Neuroscience.   
   The scientists focused on brain areas with typically the largest supply of   
   neural stem cells: an area just below several midbrain cavities filled with   
   cerebrospinal fluid, called the subventricular zone, as well as the   
   hippocampus, a major center for    
   learning and memory.   
   Mice missing ganglioside GD3 on the membranes of neural stem cells had much   
   smaller supplies of the cells in these key areas throughout life and expressed   
   signs of lost hope with behaviors such as not actively seeking dry land when   
   placed in water, Yu    
   said. Additionally, the mice had impaired maintenance of the area of the brain   
   involved in the sense of smell as well as the portion of the hippocampus that   
   enables formation of new memories.   
   The changes, which correlate with aging or illness, were corrected when GD3   
   was restored.   
   "If GD3 is missing, we found these neural stem cells cannot be maintained   
   throughout life; they are reduced by a big percentage even in a one-month-old   
   mouse," said Dr. Jing Wang, MCG postdoctoral fellow and the study's first   
   author. In fact, by one    
   month of life, there was about a 60 percent reduction in the supply and by six   
   months, which is considered aged in a mouse, there were only a handful of   
   neural stem cells remaining, Wang said.   
   The scientists note that in healthy young mice, GD3 is abundant but seems to   
   naturally decrease with age.   
   A Yu and Wang paper published in the journal PNAS in 2013 showed that GD3 is   
   the predominant ganglioside in mouse neural stem cells where it interacts with   
   epidermal growth factor receptors, also found on the cell surface. GD3 plays   
   an important role in    
   growth factor signaling, which, in turn, tells neural stem cells to   
   proliferate or die.   
   "In a normal situation, that growth factor enables the neural stem cells to   
   reproduce more stem cells," Wang said. "This gives us a better idea about how   
   our neural stem cell population is maintained over our life. Our long-term   
   goal is to use endogenous    
   neural stem cells for repair of brain or spinal cord damage, so we need to   
   learn how they proliferate, how to keep them inside the brain."   
   The two are optimistic that one day manipulating levels of growth factors and   
   sugar-containing lipids will enable a more steadfast supply of neural stem   
   cells throughout life, although getting the substances into the brain is a   
   challenge. It's already    
   known that, at least in rats, exercise can also help.   
   Neural stem cells are able to self-renew, in theory at least, forever. Their   
   ability to maintain a steady supply of themselves and to differentiate into   
   different types of brain cells are their most important properties, Yu said.   
   Next steps include examining the role of other growth factors and gangliosides.   
   Yu is the Georgia Research Alliance Eminent Scholar Chair in Molecular and   
   Cellular Neurobiology. The studies were funded by the National Institutes of   
   Health and the Veterans Administration.   
   Story Source:   
   The above story is based on materials provided by Medical College of Georgia   
   at Georgia Regents University. Note: Materials may be edited for content and   
   length.   
   Journal Reference:   
   J. Wang, A. Cheng, C. Wakade, R. K. Yu. Ganglioside GD3 Is Required for   
   Neurogenesis and Long-Term Maintenance of Neural Stem Cells in the Postnatal   
   Mouse Brain. Journal of Neuroscience, 2014; 34 (41): 13790 DOI:    
   0.1523/JNEUROSCI.2275-14.2014   
   Cite This Page:   
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   Medical College of Georgia at Georgia Regents University. "Biological fat with   
   a sugar attached essential to maintaining brain's supply of stem cells."   
   ScienceDaily.    
      
   ScienceDaily, 3 November 2014. .   
      
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