MSGID: 1:317/3 6455d7e3   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    A special omega-3 fatty acid lipid will change how we look at the   
   developing and aging brain    
      
     Date:   
         May 5, 2023   
     Source:   
         Duke-NUS Medical School   
     Summary:   
         Scientists have found a lipid transporter crucial to regulating   
         the cells that make myelin, the nerve-protecting sheath.   
      
      
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   FULL STORY   
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   Scientists from Singapore have demonstrated the critical role played by   
   a special transporter protein in regulating the brain cells that ensure   
   nerves are protected by coverings called myelin sheaths. The findings,   
   reported by researchers at Duke-NUS Medical School and the National   
   University of Singapore in the Journal of Clinical Investigation, could   
   help to reduce the damaging impacts of ageing on the brain.   
      
   An insulating membrane encasing nerves, myelin sheaths facilitate the   
   quick and effective conduction of electrical signals throughout the   
   body's nervous system. When the myelin sheath gets damaged, nerves may   
   lose their ability to function and cause neurological disorders. With   
   ageing, myelin sheaths may naturally start to degenerate, which is often   
   why the elderly lose their physical and mental abilities.   
      
   "Loss of myelin sheaths occurs during the normal ageing process and   
   in neurological diseases, such as multiple sclerosis and Alzheimer's   
   disease," said Dr Sengottuvel Vetrivel, Senior Research Fellow with   
   Duke-NUS' Cardiovascular & Metabolic Disorders (CVMD) Programme and lead   
   investigator of the study. "Developing therapies to improve myelination --   
   the formation of the myelin sheath -- in ageing and disease is of great   
   importance to ease any difficulties caused by declining myelination."   
   To pave the way for developing such therapies, the researchers   
   sought to understand the role of Mfsd2a, a protein that transports   
   lysophosphatidylcholine (LPC) -- a lipid that contains an omega-3 fatty   
   acid - - into the brain as part of the myelination process. From what is   
   known, genetic defects in the Mfsd2a gene leads to significantly reduced   
   myelination and a birth defect called microcephaly, which causes the   
   baby's head to be much smaller than it should be.   
      
   In preclinical models, the team showed that removing Mfsd2a from precursor   
   cells that mature into myelin-producing cells -- known as oligodendrocytes   
   - - in the brain led to deficient myelination after birth. Further   
   investigations, including single-cell RNA sequencing, demonstrated that   
   Mfsd2a's absence caused the pool of fatty acid molecules -- particularly   
   omega- 3 fats -- to be reduced in the precursor cells, preventing these   
   cells from maturing into oligodendrocytes that produce myelin.   
      
   "Our study indicates that LPC omega-3 lipids act as factors within the   
   brain to direct oligodendrocyte development, a process that is critical   
   for brain myelination," explained Professor David Silver, the senior   
   author of the study and Deputy Director of the CVMD Programme. "This   
   opens up potential avenues to develop therapies and dietary supplements   
   based on LPC omega-3 lipids that might help retain myelin in the ageing   
   brain -- and possibly to treat patients with neurological disorders   
   stemming from reduced myelination."  Previously, Prof Silver and his   
   lab discovered Mfsd2a and worked closely with other teams to determine   
   the function of LPC lipids in the brain and other organs. The current   
   research provides further insights into the importance of lipid transport   
   for oligodendrocyte precursor cell development.   
      
   "We're now aiming to conduct preclinical studies to determine if dietary   
   LPC omega-3 can help to re-myelinate damaged axons in the brain," added   
   Prof Silver. "Our hope is that supplements containing these fats can help   
   to maintain -- or even improve -- brain myelination and cognitive function   
   during ageing."  "Prof Silver has been relentless in investigating the   
   far-reaching role of Msdf2a ever since he discovered this important lipid   
   transport protein, alluding to the many possible ways of treating not   
   only the ageing brain but also other organs in which the protein plays a   
   role," said Professor Patrick Casey, Senior-Vice Dean for Research. "It's   
   exciting to watch Prof Silver and his team shape our understanding of the   
   roles that these specialised lipids play through their many discoveries."   
       * RELATED_TOPICS   
             o Health_&_Medicine   
                   # Brain_Tumor # Nervous_System # Healthy_Aging #   
                   Birth_Defects   
             o Mind_&_Brain   
                   # Brain_Injury # Schizophrenia # Disorders_and_Syndromes   
                   # Brain-Computer_Interfaces   
       * RELATED_TERMS   
             o Myelin o Multiple_sclerosis o Axon o Carpal_tunnel o   
             Brain_tumor o Optic_nerve o Sciatic_nerve o Pernicious_anemia   
      
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   Story Source: Materials provided by Duke-NUS_Medical_School. Note:   
   Content may be edited for style and length.   
      
      
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   Journal Reference:   
      1. Vetrivel Sengottuvel, Monalisa Hota, Jeongah Oh, Dwight L. Galam,   
      Bernice   
         H. Wong, Markus R. Wenk, Sujoy Ghosh, Federico Torta, David   
         L. Silver.   
      
         Deficiency in the omega-3 lysolipid transporter Mfsd2a   
         leads to aberrant oligodendrocyte lineage development and   
         hypomyelination. Journal of Clinical Investigation, 2023; DOI:   
         10.1172/JCI164118   
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   Link to news story:   
   https://www.sciencedaily.com/releases/2023/05/230505101659.htm   
      
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