Directional coupling of oligodendrocyte connexin‐47 and astrocyte connexin‐43 gap junctions

Fasciani, Ilaria; Pluta, Paula; González‐Nieto, Daniel; Martínez‐Montero, Paloma; Molano, Jesús; Paı́no, Carlos Luis; Millet, Óscar; Barrio, Luis C.

doi:10.1002/glia.23471

Cited by 46 publications

(31 citation statements)

References 49 publications

(106 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Gap junctions provide a bidirectional route for interaction between oligodendrocytes and astrocytes [4][5][6], where specific connexin proteins form the intercellular channels in the different cells. Astrocytes express Cx43 (Gja1) and Cx30 (Gjb6), whereas oligodendrocytes express Cx32 (Gjb1) and Cx47 (Gja12), and the two cell types communicate through heterotypic connexin pairing (Cx43:Cx47, Cx30:Cx32) [7].…”

Section: Introductionmentioning

confidence: 99%

Cellular Environment Remodels the Genomic Fabrics of Functional Pathways in Astrocytes

Iacobaş

Stout

et al. 2020

Genes

View full text Add to dashboard Cite

We profiled the transcriptomes of primary mouse cortical astrocytes cultured alone or co-cultured with immortalized precursor oligodendrocytes (Oli-neu cells). Filters between the cell types prevented formation of hetero-cellular gap junction channels but allowed for free exchange of the two culture media. We previously reported that major functional pathways in the Oli-neu cells are remodeled by the proximity of non-touching astrocytes and that astrocytes and oligodendrocytes form a panglial transcriptomic syncytium in the brain. Here, we present evidence that the astrocyte transcriptome likewise changes significantly in the proximity of non-touching Oli-neu cells. Our results indicate that the cellular environment strongly modulates the transcriptome of each cell type and that integration in a heterocellular tissue changes not only the expression profile but also the expression control and networking of the genes in each cell phenotype. The significant decrease of the overall transcription control suggests that in the co-culture astrocytes are closer to their normal conditions from the brain. The Oli-neu secretome regulates astrocyte genes known to modulate neuronal synaptic transmission and remodels calcium, chemokine, NOD-like receptor, PI3K-Akt, and thyroid hormone signaling, as well as actin-cytoskeleton, autophagy, cell cycle, and circadian rhythm pathways. Moreover, the co-culture significantly changes the gene hierarchy in the astrocytes.

show abstract

Section: Introductionmentioning

confidence: 99%

Cellular Environment Remodels the Genomic Fabrics of Functional Pathways in Astrocytes

Iacobaş

Stout

et al. 2020

Genes

View full text Add to dashboard Cite

show abstract

“…In the white and gray matter, Cx47 localizes in the cell body and initial processes of oligodendrocytes, as well as in the abaxonal membrane of myelinated fibers (Nagy et al, 2003; Altevogt and Paul, 2004; Kleopa et al, 2004; Kamasawa et al, 2005). In those cell areas Cx47 may form homotypic Cx47/Cx47 GJCs among oligodendrocytes and heterotypic GJCs with astrocytes expressing Cx43 (see next section; Figure 2; Wasseff and Scherer, 2011; Fasciani et al, 2018).…”

Section: Oligodendrocyte-oligodendrocyte Gap Junctional Communicationmentioning

confidence: 99%

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

Vejar

Oyarzún

Retamal

et al. 2019

Front. Cell. Neurosci.

View full text Add to dashboard Cite

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.

show abstract

“…Astrocytes are the most common cells in the CNS and have multiple functions. In healthy conditions astrocytes regulate the concentration of different neurotransmitters and ions, supply various metabolites and energy, regulate osmolarity, modulate synaptic activity, secrete neurotrophic and neuroprotective factors, promote neurogenesis ( Allen and Eroglu, 2017 ; Verkhratsky et al, 2017 ) and remyelination ( Fasciani et al, 2018 ), play a role in immune-modulation ( Liddelow and Barres, 2017 ) and blood-brain barrier formation ( Sweeney et al, 2019 ) as well as in the glymphatic system ( Louveau et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Rising Stars: Astrocytes as a Therapeutic Target for ALS Disease

Izrael¹,

Slutsky²,

Revel

2020

Front. Neurosci.

View full text Add to dashboard Cite

Amyotrophic lateral sclerosis (ALS) is a multifactorial disease, characterized by a progressive loss of motor neurons that eventually leads to paralysis and death. The current ALS-approved drugs modestly change the clinical course of the disease. The mechanism by which motor neurons progressively degenerate remains unclear but entails a non-cell autonomous process. Astrocytes impaired biological functionality were implicated in multiple neurodegenerative diseases, including ALS, frontotemporal dementia (FTD), Parkinson's disease (PD), and Alzheimer disease (AD). In ALS disease patients, A1 reactive astrocytes were found to play a key role in the pathology of ALS disease and death of motor neurons, via loss or gain of function or acquired toxicity. The contribution of astrocytes to the maintenance of motor neurons by diverse mechanisms makes them a promising therapeutic candidate for the treatment of ALS. Therapeutic approaches targeting at modulating the function of endogenous astrocytes or replacing lost functionality by transplantation of healthy astrocytes, may contribute to the development of therapies which might slow down or even halt the progression ALS diseases. The proposed mechanisms by which astrocytes can potentially ameliorate ALS progression and the status of ALS clinical studies involving astrocytes are discussed.

show abstract

Directional coupling of oligodendrocyte connexin‐47 and astrocyte connexin‐43 gap junctions

Cited by 46 publications

References 49 publications

Cellular Environment Remodels the Genomic Fabrics of Functional Pathways in Astrocytes

Cellular Environment Remodels the Genomic Fabrics of Functional Pathways in Astrocytes

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

Rising Stars: Astrocytes as a Therapeutic Target for ALS Disease

Contact Info

Product

Resources

About