Evidence of decreased gap junction coupling between astrocytes and oligodendrocytes in the anterior cingulate cortex of depressed suicides

摘要: ABSTRACT Glial dysfunction is a major feature in the pathophysiology of mood disorders. While altered astrocyte (AS) and oligodendrocyte-lineage (OL) cell functions have been associated with depression, crosstalk between these two glial types has never assessed that context. AS are potent regulators OL cells myelination, part through gap junction-mediated intercellular communication made possible by heterotypic coupling AS-specific (Cx30 Cx43) OL-specific (Cx32 Cx47) connexins, allowing cytosolic transport metabolic support to cells. Because changes expression connexins previously reported brain depressed individuals, this study aimed at addressing integrity AS-OL anterior cingulate cortex (ACC) suicides. Using immunofluorescence confocal imaging, we characterized distribution Cx30 ACC, mapped its onto oligodendrocyte somas myelinated axons as well vasculature post-mortem samples from suicides (N=48) matched controls (N=23). The differential gene key components junction nexus was also screened RNA-sequencing dataset generated our group, validated quantitative real-time PCR. Our results indicate mapping selectively decreased suicides, an effect Cx32 Cx47, downregulation connexin-interacting proteins essential for scaffolding, trafficking function channels. These provide first evidence impaired mediated astrocytes oligodendrocytes ACC individuals likely significant impact on function, may contribute region.