title: [Connexin astrocytopathy and novel therapeutic strategy targeting connexin hemichannels in demyelinating disease].
abstract: Recently, we reported aquaporin-4 (AQP4) loss without perivascular deposition of complements or immunoglobulins in autopsied cases with multiple sclerosis (MS), neuromyelitis optica (NMO) and Baló's disease (BD). To investigate the relationship between astrocytopathy and demyelination, we examined the expression of connexins (Cx), which form gap junction channels between astrocytes and oligodendrocytes. We pathologically evaluated the expressions of astrocytic Cx43/Cx30 and oligodendroglial Cx47/Cx32 relative to those of other astrocytic and oligodendrocyte/myelin markers among the autopsied cases. In all BD cases, Cx43, Cx32 and Cx47 were extensively diminished. In the leading edge of Baló's lesions, Cx43 and AQP4 loss preceded Cx47 loss. Two cases with MS and six with 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. The other cases showed AQP4 and Cx43 preservation. 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.
authors.affiliation: Department of Neurology, Graduate School of Medical Sciences, Kyushu University.
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Masaki
mesh_terms: D051401:Aquaporin 4 / Q000032:analysis; D001253:Astrocytes / Q000473:pathology*; D017630:Connexins / Q000032:analysis* / Q000502:physiology; D003711:Demyelinating Diseases / Q000473:pathology* / Q000628:therapy; D002549:Diffuse Cerebral Sclerosis of Schilder / Q000473:pathology; D006801:Humans; D009103:Multiple Sclerosis / Q000473:pathology; D009471:Neuromyelitis Optica / Q000473:pathology; D009836:Oligodendroglia / Q000473:pathology
chemical_list: D051401:Aquaporin 4; D017630:Connexins