Connexin astrocytopathy in the pathogenesis of demyelination in concentric sclerosis and multiple sclerosis

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To investigate the relationship between astrocytopathy and demyelination, we examined the expression of connexins (Cx). We pathologically evaluated the expressions of astrocytic Cx43/Cx30 and oligodendroglial Cx47/Cx32 among autopsied cases with demyelinating disorders. In Balo’ s disease (BD), Cx43, Cx32 and Cx47 were extensively diminished. In the leading edge of Balo’s lesions, Cx43 and AQP4 loss preceded Cx47 loss. Three cases with multiple sclerosis (MS) and six with neuromyelitis optica (NMO) showed preferential Cx43 and AQP4 loss far beyond the demyelinated areas, while vasculocentric deposition of immunoglobulins or complements was observed in four of the six NMO cases. Some NMO cases showed preferential myelin-associated glycoprotein (MAG) loss in AQP4- and Cx43-diminished active lesions. Our findings indicate that disruption of Cx gap junction and preferential MAG loss could occur in MS, BD and NMO, and could be a common denominator. Inhibition of Cx hemichannels is a possible therapeutic target for demyelinating disorders