Recent advances in understanding connexin gap junction pathology in demyelinating diseases

AbstractMultiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD) and Bal ó’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 a nd 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 oligodendrogliopath...
Source: Clinical and Experimental Neuroimmunology - Category: Neurology Authors: Tags: REVIEW ARTICLE Source Type: research