Recent advances in understanding connexin gap junction pathology in demyelinating diseases

研究成果: Contribution to journalArticle査読

抄録

Multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD) and Baló’s disease (BD) are inflammatory demyelinating diseases of the central nervous system. We previously reported that aquaporin-4 antibody-independent astrocytopathy can occur in heterogeneous demyelinating conditions. We focused on connexins (Cxs), which form gap junctions between astrocytes and oligodendrocytes to form the glial syncytium of the central nervous system. We investigated the pathological expression pattern of Cx43/Cx30 in astrocytes, and Cx47/Cx32 in oligodendrocytes in autopsied samples from MS, NMOSD and BD. Astrocytic Cx43 and oligodendrocytic Cx32/Cx47 were extensively diminished in both demyelinated and myelinated layers in all BD cases. Half of the NMOSD and MS cases showed preferential loss of astrocytic Cx43 in active demyelinating and chronic active lesions, where heterotypic Cx43/Cx47 astrocyte-oligodendrocyte gap junctions were widely lost. Loss of Cx43 was frequently accompanied by distal oligodendrogliopathy, which is characterized by a preferential loss of myelin-associated glycoprotein and apoptotic-like oligodendrocytes. Isolated perivascular lesions in the spinal cord of NMOSD cases showed loss of aquaporin-4 and Cx43, indicating early involvement of Cx43 in NMOSD. Neuronal and glial Cxs were affected in gray matter demyelination in MS and neurodegenerative diseases. Our findings show that Cx43 astrocytopathy and Cx47/Cx32 oligodendrogliopathy can be seen in MS, BD and NMOSD. Furthermore, the loss of astrocytic Cx43 might be associated with disease aggressiveness and distal oligodendrogliopathy in demyelinating conditions. Early disruption of glial gap junctions might disturb the glial syncytium and disrupt intercell communication, thereby inducing oligodendroglial injury and subsequent demyelination.

本文言語英語
ページ(範囲)4-13
ページ数10
ジャーナルClinical and Experimental Neuroimmunology
11
S1
DOI
出版ステータス出版済み - 3 1 2020
外部発表はい

All Science Journal Classification (ASJC) codes

  • 神経科学(その他)
  • 免疫学
  • 免疫学および微生物学(その他)
  • 臨床神経学

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