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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