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

Glial dysfunction is a major pathophysiological feature of mood disorders. While altered astrocyte (AS) and oligodendrocyte-lineage (OL) functions have been associated with depression, the crosstalk between these glial cell types has never been assessed in that context. AS are potent regulators of m...

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Published in:Neuropsychopharmacology 2019-11, Vol.44 (12), p.2099-2111
Main Authors: Tanti, Arnaud, Lutz, Pierre-Eric, Kim, John, O'Leary, Liam, Théroux, Jean-François, Turecki, Gustavo, Mechawar, Naguib
Format: Article
Language:English
Subjects:
Astrocytes
Astrocytes - metabolism
Autopsy
Axons
Brain
Connexin 30 - metabolism
Connexin 32
Connexin 43
Connexins
Connexins - metabolism
Cortex (cingulate)
Depressive Disorder - metabolism
Emotional disorders
Fibers
Gene expression
Gyrus Cinguli - metabolism
Humans
Immunofluorescence
Life Sciences
Mental depression
Mood
Myelination
Nerve Fibers, Myelinated - metabolism
Neuroimaging
Oligodendrocytes
Oligodendroglia - metabolism
Regulators
Ribonucleic acid
RNA
Suicide, Completed - psychology
Suicides & suicide attempts
Trafficking
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Summary:Glial dysfunction is a major pathophysiological feature of mood disorders. While altered astrocyte (AS) and oligodendrocyte-lineage (OL) functions have been associated with depression, the crosstalk between these glial cell types has never been assessed in that context. AS are potent regulators of myelination, in part through gap junction (GJ) channels formed by the heterotypic coupling of AS-specific (Cx30 and Cx43) and OL-specific (Cx32 and Cx47) connexins. This study therefore aimed at addressing the integrity of AS/OL coupling in the anterior cingulate cortex (ACC) of depressed suicides. Using immunofluorescence and confocal imaging, we characterized the distribution of Cx30 and mapped its expression onto OL somas, myelinated axons, and brain vasculature in postmortem brain samples from depressed suicides (N = 48) and matched controls (N = 23). Differential gene expression of key components of the GJ nexus was also screened through RNA-sequencing previously generated by our group, and validated by quantitative real-time PCR. We show that Cx30 expression localized onto OL cells and myelinated fibers is decreased in deep cortical layers of the ACC in male-depressed suicides. This effect was associated with decreased expression of OL-specific connexins, as well as the downregulation of major connexin-interacting proteins essential for the scaffolding, trafficking, and function of GJs. These results provide a first evidence of impaired AS/OL GJ-mediated communication in the ACC of individuals with mood disorders. These changes in glial coupling are likely to have significant impact on brain function, and may contribute to the altered OL function previously reported in this brain region.
ISSN:0893-133X
1740-634X
0007-0920
DOI:10.1038/s41386-019-0471-z