Connexin and Pannexin-Based Channels in Oligodendrocytes: Implications in Brain Health and Disease

Abstract

Oligodendrocytes are the myelin forming cells in the central nervous system (CNS). In addition to this main physiological function, these cells play key roles by providing energy substrates to neurons as well as information required to sustain proper synaptic transmission and plasticity at the CNS. The latter requires a fine coordinated intercellular communication with neurons and other glial cell types, including astrocytes. In mammals, tissue synchronization is mainly mediated by connexins and pannexins, two protein families that underpin the communication among neighboring cells through the formation of different plasma membrane channels. At one end, gap junction channels (GJCs; which are exclusively formed by connexins in vertebrates) connect the cytoplasm of contacting cells allowing electrical and metabolic coupling. At the other end, hemichannels and pannexons (which are formed by connexins and pannexins, respectively) communicate the intra- and extracellular compartments, serving as diffusion pathways of ions and small molecules. Here, we briefly review the current knowledge about the expression and function of hemichannels, pannexons and GJCs in oligodendrocytes, as well as the evidence regarding the possible role of these channels in metabolic and synaptic functions at the CNS. In particular, we focus on oligodendrocyte-astrocyte coupling during axon metabolic support and its implications in brain health and disease.

Cellular Environment Remodels the Genomic Fabrics of Functional Pathways in Astrocytes

“…These studies revealed that the brain transcriptomes of Cx43KO mouse and Cx32KO mouse were both 83% altered with respect to the wildtype counterpart, whereas their similarity to the brain of Cx36KO mouse were respectively 12% and 11% [12]. Since astrocytes and oligodendrocytes form heterocellular gap junction channels with each other [14][15][16], but none with neurons has been yet reported in the mouse brain (after our knowledge), these results suggested "panglial transcriptomic continuity". By transcriptomic continuity we understand that transcriptomic changes in one cell type has consequences in another cell type.…”

Connexins-Based Hemichannels/Channels and Their Relationship with Inflammation, Seizures and Epilepsy

“…They mainly contribute to conduction inside neuronal circuits, but they also participate in metabolic supply and ion buffering [81,82]. Oligodendrocytes mainly express Cx29, Cx32, and Cx47; through these connections, they form channels with astrocytes and with themselves (heterotypic unions of Cx30 and Cx32, and of Cx43 and Cx47) [7,83]. These functional unions of Cxs even participate in the release of gliotransmitters, although it is not clear if oligodendrocytes have the necessary molecular machinery to fulfill this task [84].…”

Multiple sclerosis iPSC-derived oligodendroglia conserve their intrinsic properties to functionally interact with axons and glia in vivo

“…These intercellular interactions between competing oligodendroglial cells influence the number and length of myelin internodes as well as the initiation of differentiation (54,55). Oligodendrocytes are also coupled to astrocytes through heterologous gap junctions such as Cx32/Cx30 and Cx47/Cx43 (56). Disruption of oligodendrocytes from each other and from astrocytes, i.e.…”