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世界の幹細胞(関連)論文紹介


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Oligodendroglia Cells Can Do Much More Than an Insulator for Neuron

論文紹介著者

Raye Zhan(博士課程 4年)

Raye Zhan(博士課程 4年)
GCOE RA
漢方医学センター

第一著者名・掲載雑誌・号・掲載年月

Youngjin Lee/Nature.vol 487.443-448.11 July 2012

文献の英文表記:著者名・論文の表題・雑誌名・巻・号・ページ・発行年(西暦)

Youngjin Lee, Brett M. Morrison, Yun Li, Sylvain Lengacher, Mohamed H. Farah, Paul N. Hoffman, Yiting Liu, Akivaga Tsingalia, Lin Jin, Ping-Wu Zhang, Luc Pellerin, Pierre J. Magistretti, Jeffrey D. Rothstein. Oligodendroglia metabolically support axons and contribute to neurodegeneration. Nature. 487:443-448.2012

論文解説

Metabolic support for neurons

Blood glucose (orange) can be taken up by non-neuronal brain cells known as oligodendrocytes and astrocytes. Inside the cells, glucose is broken down to lactate (blue), which can then be transferred to neurons and used to generate metabolic energy in the form of ATP molecules (yellow). Lee et al. show that oligodendrocytes supply nerve fibres (axons) with lactate delivered through a transporter protein (MCT1, not shown) located in the myelin, a membranous sheath around the axons. Lactate can also be produced in astrocytes and then transferred to axons by means of small pores (gap junctions, not shown) through the myelin. In addition, blood lactate may reach neurons through astrocytes and oligodendrocytes.

Image Source: reproduced from www.nature.com
http://www.nature.com/nature/journal/v487/n7408/full/487435a.html

Oligodendroglia cells are long considered to be responsible for promoting rapid conduction of action potentials by formation of the fat-rich myelin sheath which surrounds the nerve fibers as an insulating layer. However, researchers at Johns Hopkins University have discovered that the function of the oligodendrocytes goes far beyond simply insulating nerves,they are also vital to the survival of neurons by supplying lactate that axons can take up and use for energy. Damage to Oligodendroglia cells may lead to serious neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). This discovery may provide a new understanding of the role of oligodendrocytes and novel therapeutic target for ALS as well as potentially other neurodegenerative disease.

Firstly, the researchers modified mice to promise whose cells would light up if MCT1 was expressed. The result showed that MCT1 is highly located on oligodendrocytes in the brain and spinal cord. Next, they turned off the activity of the MCT1 gene in cell culture and found that neuron began to die. Similarly, the use of inhibitor for MCT1 in slices of spinal cord grown in a culture dish got the same result. Finally, the research team found that significant loss of MCT1 in brains of people with ALS and mouse models of the disease.

All the findings suggest that this newly discovered axon-feeding mechanism may play an important role in neurodegenerative disease, and therapy focusing on increasing lactate supply may stop or slow down the progression of the neurodegenerative disease.

用語解説

  • ※1 Amyotrophic lateral sclerosis (ALS):
    often referred to as "Lou Gehrig's Disease," is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. Motor neurons reach from the brain to the spinal cord and from the spinal cord to the muscles throughout the body. The progressive degeneration of the motor neurons in ALS eventually leads to their death. When the motor neurons die, the ability of the brain to initiate and control muscle movement is lost. With voluntary muscle action progressively affected, patients in the later stages of the disease may become totally paralyzed.
  • ※2 Monocarboxylate transporters (MCT):
    a family of proton-linked plasma membrane transporters that carry molecules having one carboxylate group (monocarboxylates), such as lactate, pyruvate as well as ketone bodies, across biological membranes. The differences in the properties of MCT isoforms are related to the metabolic requirements of the tissue in which they are expressed.

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