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神経科学学会-神経学会合同シンポジウム:Neuroimmunology Cutting Edge Symposium: Mechanisms of Immune-mediated Neurological Disease
Joint Symposium of the Japan Neuroscience Society and the Japanese Society of Neurology:Neuroimmunology Cutting Edge Symposium:
Mechanisms of Immune-mediated Neurological Disease

開催日 2014/9/13
時間 9:00 - 11:00
会場 Room A(Main Hall)
Chairperson(s) 吉良 潤一 / Jun-ichi Kira (九州大学大学院医学系研究院 神経内科学 / Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Japan)
神田 隆 / Takashi Kanda (山口大学大学院医学系研究科神経内科学 / Department of Neurology and Clinical Neuroscience, Yamaguchi University Graduate School of Medicine, Japan)

Early Disruption of the Glial Syncytium via Connexins and Energy Transporters in Demyelinating Disorders

  • S3-A-1-1
  • 吉良 潤一 / Jun-ichi Kira:1 真崎 勝久 / Katsuhisa Masaki:1 
  • 1:九州大学 / Kyushu University, Japan 

Recently, energy supply to axons via glial cells has received a lot of attention. Nutritional substances such as glucose and lactate are transferred from blood vessels to axons via connexins (Cxs), glucose transporters (GLUTs) and monocarboxylate transporters (MCTs). Cxs form gap junctions between astrocytes, or between astrocytes and oligodendrocytes. Gap junctions form channels for direct intercellular communication through which intracellular second messengers are exchanged. We observed extensive loss of Cx43, Cx32 and Cx47 in demyelinated and myelin-preserved layers of acute lesions from patients with Balos concentric sclerosis, a rare and extremely severe variant of multiple sclerosis (MS). In the leading edge areas, where expression of myelin-associated glycoprotein (MAG) is partly diminished with other myelin proteins well preserved, similar to distal oligodendrogliopathy, astrocytic Cx43 is completely lost. Similar changes were also observed in MS and neuromyelitis optica cases culminating in death within 2 years after disease onset. These findings suggest that early disruption of Cxs may cause the extensive energy failure and contribute to the pathogenesis of demyelinating disorders. To gain a better understanding of the metabolic condition, we studied the expression of GLUTs and MCTs in demyelinating lesions. We pathologically evaluated six autopsied cases with MS and 20 cases with other neurological diseases. We evaluated the expression of GLUT1, 3, 4, 5 and MCT1, 2, 4 relative to expression level of glial fibrillary acidic protein, and the extent of demyelination. We also evaluated immunoreactivities for myelin basic protein, myelin oligodendrocyte glycoprotein, Nogo-A, neurofilament and amyloid precursor protein, and performed lesion staging on the basis of CD68 staining. In active MS lesions, despite massive perivascular lymphocytic cuffing, endothelial MCT1 and GLUT1 were relatively preserved. Conversely, immunoreactivity for astrocytic MCT4 was diminished in the perivascular foot processes. Microglial GLUT5 was up-regulated in activated microglia and foamy macrophages. Immunoreactivity for APP and GLUT3 was found in damaged axons. Our findings indicate that the expression of GLUTs and MCTs is altered in active MS lesions, and this alteration may cause energy failure in the early stage of MS.

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