Astroglial Cx30 sustains neuronal population bursts independently of gap‐junction mediated biochemical coupling

Pannasch, Ulrike; Dossi, Elena; Ezan, Pascal; Rouach, Nathalie

doi:10.1002/glia.23591

Cited by 14 publications

(10 citation statements)

References 58 publications

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“…10e). Specific top gene markers representing each subcluster were found across major astroglial functions, including synapse function/plasticity (C1ql2 28,29 , Agt 30 ), neurotransmission (Slc39a12 31,32 ), gap junction (Gjb6 33,34 ), and ion modulation/ binding (Kcnj8 35 , Pln 36 ) (Fig. 10f).…”

Section: Hemorrhagic Stroke Ischemic Strokementioning

confidence: 99%

Stroke subtype-dependent synapse elimination by reactive gliosis in mice

et al. 2021

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The pathological role of reactive gliosis in CNS repair remains controversial. In this study, using murine ischemic and hemorrhagic stroke models, we demonstrated that microglia/macrophages and astrocytes are differentially involved in engulfing synapses in the reactive gliosis region. By specifically deleting MEGF10 and MERTK phagocytic receptors, we determined that inhibiting phagocytosis of microglia/macrophages or astrocytes in ischemic stroke improved neurobehavioral outcomes and attenuated brain damage. In hemorrhagic stroke, inhibiting phagocytosis of microglia/macrophages but not astrocytes improved neurobehavioral outcomes. Single-cell RNA sequencing revealed that phagocytosis related biological processes and pathways were downregulated in astrocytes of the hemorrhagic brain compared to the ischemic brain. Together, these findings suggest that reactive microgliosis and astrogliosis play individual roles in mediating synapse engulfment in pathologically distinct murine stroke models and preventing this process could rescue synapse loss.

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Section: Hemorrhagic Stroke Ischemic Strokementioning

confidence: 99%

Stroke subtype-dependent synapse elimination by reactive gliosis in mice

et al. 2021

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“…and Glastastrocytes in the cortex [8], and coordinated with the different neurons around them. In addition, Cx30astrocytes lack gap junctions and do not express Cx30 but instead express other connexins in the CeC that are relevant to specific functions [52,53]. When driven by Fgfr3, Cre recombinase showed leakage throughout the brain, and this may trigger developmental effects.…”

Section: Discussionmentioning

confidence: 99%

Expression Patterns of Inducible Cre Recombinase Driven by Differential Astrocyte-Specific Promoters in Transgenic Mouse Lines

Chen

Wang

et al. 2019

Neurosci. Bull.

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Astrocytes are the most abundant cell type in the central nervous system (CNS). They provide trophic support for neurons, modulate synaptic transmission and plasticity, and contribute to neuronal dysfunction. Many transgenic mouse lines have been generated to obtain astrocyte-specific expression of inducible Cre recombinase for functional studies; however, the expression patterns of inducible Cre recombinase in these lines have not been systematically characterized. We generated a new astrocyte-specific Aldh1l1-CreER T2 knock-in mouse line and compared the expression pattern of Cre recombinase between this and five widely-used transgenic lines (hGfap-CreER T2 from The Jackson Laboratory and The Mutant Mouse Resource and Research Center, Glast-CreER T2 , Cx30-CreER T2 , and Fgfr3-iCreER T2 ) by crossing with Ai14 mice, which express tdTomato fluorescence following Cre-mediated recombination. In adult Aldh1l1-CreER T2 :Ai14 transgenic mice, tdTomato was detected throughout the CNS, and five novel morphologicallydefined types of astrocyte were described. Among the six evaluated lines, the specificity of Cre-mediated recombination was highest when driven by Aldh1l1 and lowest when driven by hGfap; in the latter mice, co-staining between tdTomato and NeuN was observed in the hippocampus and cortex. Notably, evident leakage was noted in Fgfr3-iCreER T2 mice, and the expression level of tdTomato was low in the thalamus when Cre recombinase expression was driven by Glast and in the capsular part of the central amygdaloid nucleus when driven by Cx30. Furthermore, tdTomato was clearly expressed in peripheral organs in four of the lines. Our results emphasize that the astrocyte-specific CreER T2 transgenic lines used in functional studies should be carefully selected.

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“…Astrocytes also have impaired interactions with cell types other than neurons, as they have fewer vascular contacts and form fewer gap junctions composed of connexin 30 with oligodendrocytes (Ernst et al, 2011;Miguel-Hidalgo et al, 2014;Rajkowska, Hughes, Stockmeier, Javier Miguel-Hidalgo, & Maciag, 2013;Tanti et al, 2019). However, VIM-IR astrocytes have a mostly unaltered morphological profile in MDD patients, and this is surprising given that connexin 30 is known to regulate astrocyte morphology (O'Leary et al, 2021;Pannasch et al, 2019). While altered astrocyte morphology has been previously reported for Golgi staining in the anterior cingulate cortical white matter of depressed suicides, this has not been observed for VIM-IR astrocytes in four other areas of the brain which showed lower VIM-IR astrocyte densities in depressed suicides (O'Leary et al, 2021;Torres-Platas et al, 2011).…”

Section: Astrocyte Loss In Mddmentioning

confidence: 99%

Implication of cerebral astrocytes in major depression: A review of fine neuroanatomical evidence in humans

O’Leary

Mechawar

2021

Glia

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Postmortem investigations have implicated astrocytes in many neurological and psychiatric conditions. Multiple brain regions from individuals with major depressive disorder (MDD) have lower expression levels of astrocyte markers and lower densities of astrocytes labeled for these markers, suggesting a loss of astrocytes in this mental illness. This paper reviews the general properties of human astrocytes, the methods to study them, and the postmortem evidence for astrocyte pathology in MDD. When comparing astrocyte density and morphometry studies, astrocytes are more abundant and smaller in human subcortical than cortical brain regions, and immunohistochemical labeling for the astrocyte markers glial fibrillary acidic protein (GFAP) and vimentin (VIM) reveals fewer than 15% of all astrocytes that are present in cortical and subcortical regions, as revealed using other staining techniques. By combining astrocyte densities and morphometry, a model was made to illustrate that domain organization is mostly limited to GFAP‐IR astrocytes. Using these markers and others, alterations of astrocyte densities appear more widespread than those for astrocyte morphologies throughout the brain of individuals having died with MDD. This review suggests how reduced astrocyte densities may relate to the association of depressive episodes in MDD with elevated S100 beta (S100B) cerebrospinal fluid serum levels. Finally, a potassium imbalance theory is proposed that integrates the reduced astrocyte densities generated from postmortem studies with a hypothesis for the antidepressant effects of ketamine generated from rodent studies.

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Astroglial Cx30 sustains neuronal population bursts independently of gap‐junction mediated biochemical coupling

Cited by 14 publications

References 58 publications

Stroke subtype-dependent synapse elimination by reactive gliosis in mice

Stroke subtype-dependent synapse elimination by reactive gliosis in mice

Expression Patterns of Inducible Cre Recombinase Driven by Differential Astrocyte-Specific Promoters in Transgenic Mouse Lines

Implication of cerebral astrocytes in major depression: A review of fine neuroanatomical evidence in humans

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