An emerging role of astrocytes in aging/neuroinflammation and gut-brain axis with consequences on sleep and sleep disorders

Gudkov, Sergey V.; Burmistrov, Dmitriy; Kondakova, Elena; Sarimov, Ruslan M.; Yarkov, Roman S.; Franceschi, Claudio; Vedunova, Maria

doi:10.1016/j.arr.2022.101775

Cited by 25 publications

(22 citation statements)

References 288 publications

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“…MMCCI was able to provide relevant biological insights into the multimodal aging mouse brain and melanoma datasets that may not have been observable if only one sample or modality was analyzed. In the aging brain, astrocytes were shown to become more active, not only increasing their interaction strength but also the types of LR interactions, which is consistent with the current understanding of the roles of astrocytes in aging [27, 28, 29, 30, 31, 32, 33, 34, 35]. The thinning of the ependymal layer expected in aging was also shown by the observed decrease in ependymal interactions in aging [25, 26].…”

Section: Discussionsupporting

confidence: 76%

MMCCI: multimodal integrative analysis of single-cell and spatial cell-type communications to uncover overarching and condition-specific ligand-receptor interaction pathways

Hockey,

Mulay,

Xiong

et al. 2024

Preprint

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Cell-cell interaction (CCI) analyses are becoming an indispensable discovery tool for cutting-edge single cell and spatial omics technologies, identifying ligand-receptor (LR) targets in intercellular communications at the molecular, cellular, and microenvironment levels. Different transcriptional-based modalities can add complementary information and provide independent validation of a CCI, but so far no robust methods exist to integrate CCI results together. To address this, we have developed a statistical and computational pipeline, Multimodal CCI (MMCCI), implemented in an open-source Python package, which integrates, analyzes, and visualizes multiple LR-cell-type CCI networks between multiple samples of a single transcriptomic-based modality as well as between multiple modalities. MMCCI implements new and in-depth downstream analyses, including comparison between biological conditions, network and interaction clustering, sender-receiver interaction querying, and pathway analysis. We applied MMCCI to integrate CCIs in our spatial transcriptomics datasets of aging mouse brains (from 10X Visium and BGI STOmics) and melanoma (10X Visium, 10X Xenium and NanoString CosMx) and identified biologically meaningful interactions. Using simulated data, we applied MMCCI integration on four popular CCI algorithms, stLearn, CellChat, Squidpy, and NATMI, and detected highly confident interactions while reducing false interaction discoveries through the integration of multiple samples. With MMCCI, the community will have access to a valuable tool for harnessing the power of multimodal single cell and spatial transcriptomics. MMCCI source code and documentation are available at:https://github.com/BiomedicalMachineLearning/MultimodalCCI.

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Section: Discussionsupporting

confidence: 76%

MMCCI: multimodal integrative analysis of single-cell and spatial cell-type communications to uncover overarching and condition-specific ligand-receptor interaction pathways

Hockey,

Mulay,

Xiong

et al. 2024

Preprint

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“…Several studies have demonstrated an increase in the number of GFAP-positive astrocytes [31][32][33], while others have observed a decrease [34,35] or no change [25]. Additionally, both hypertrophy and atrophy of GFAP-positive astrocytes have been observed with regional specificity [2,31,36,37].…”

Section: Discussionmentioning

confidence: 99%

“…Calcium waves enable the regulation of the release of gliotransmitters such as glutamate and ATP and affect the expression of various genes. Consequently, these effects can have an impact on neighboring astrocytes, microglial cells, synaptic plasticity, and neuronal excitability [2,5].…”

Section: Of 17mentioning

confidence: 99%

“…They perform homeostatic functions, including the maintenance of extracellular ion homeostasis, the regulation of energy metabolism of neurons, and neurovascular interaction. Astrocytes are also involved in the regulation of synaptic plasticity and neuronal excitability through the release of neuroactive substances called gliotransmitters [2]. Given their diverse functions, investigating the physiological characteristics of astrocytes is important for gaining insights into the underlying mechanisms of aging and its etiology.…”

Section: Introductionmentioning

confidence: 99%

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Unravelling the Collective Calcium Dynamics of Physiologically Aged Astrocytes under a Hypoxic State In Vitro

Mitroshina,

Krivonosov,

Pakhomov

et al. 2023

IJMS

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Astrocytes serve many functions in the brain related to maintaining nerve tissue homeostasis and regulating neuronal function, including synaptic transmission. It is assumed that astrocytes are crucial players in determining the physiological or pathological outcome of the brain aging process and the development of neurodegenerative diseases. Therefore, studies on the peculiarities of astrocyte physiology and interastrocytic signaling during aging are of utmost importance. Calcium waves are one of the main mechanisms of signal transmission between astrocytes, and in the present study we investigated the features of calcium dynamics in primary cultures of murine cortical astrocytes in physiological aging and hypoxia modeling in vitro. Specifically, we focused on the assessment of calcium network dynamics and the restructuring of the functional network architecture in primary astrocytic cultures. Calcium imaging was performed on days 21 (“young” astrocyte group) and 150 (“old” astrocyte group) of cultures’ development in vitro. While the number of active cells and frequency of calcium events were decreased, we observed a reduced degree of correlation in calcium dynamics between neighboring cells, which was accompanied by a reduced number of functionally connected cells with fewer and slower signaling events. At the same time, an increase in the mRNA expression of anti-apoptotic factor Bcl-2 and connexin 43 was observed in “old” astrocytic cultures, which can be considered as a compensatory response of cells with a decreased level of intercellular communication. A hypoxic episode aggravates the depression of the connectivity of calcium dynamics of “young” astrocytes rather than that of “old” ones.

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“…In addition, morphologically different astrocytes in different parts of the brain have been described. Regional heterogeneity of astrocytes has been shown to underlie different responses to treatment for bacterial infections, stroke, and possibly Norrie disease (Gudkov et al, 2023). Probably, further studies will reveal the features of cell death and the role of heterogeneity of astrocytic populations in various CNS diseases.…”

Section: Necroptosis and Astrocytesmentioning

confidence: 99%

Necroptosis in CNS diseases: Focus on astrocytes

Митрошина

Savyuk

Vedunova

2023

Front. Aging Neurosci.

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In the last few years, necroptosis, a recently described type of cell death, has been reported to play an important role in the development of various brain pathologies. Necroptosis is a cell death mechanism that has morphological characteristics similar to necrosis but is mediated by fundamentally different molecular pathways. Necroptosis is initiated by signaling through the interaction of RIP1/RIP3/MLKL proteins (receptor-interacting protein kinase 1/receptor-interacting protein kinase 3/mixed lineage kinase domain-like protein). RIPK1 kinase is usually inactive under physiological conditions. It is activated by stimulation of death receptors (TNFR1, TNFR2, TLR3, and 4, Fas-ligand) by external signals. Phosphorylation of RIPK1 results in the formation of its complex with death receptors. Further, complexes with the second member of the RIP3 and MLKL cascade appear, and the necroptosome is formed. There is enough evidence that necroptosis plays an important role in the pathogenesis of brain ischemia and neurodegenerative diseases. In recent years, a point of view that both neurons and glial cells can play a key role in the development of the central nervous system (CNS) pathologies finds more and more confirmation. Astrocytes play complex roles during neurodegeneration and ischemic brain damage initiating both impair and protective processes. However, the cellular and molecular mechanisms that induce pathogenic activity of astrocytes remain veiled. In this review, we consider these processes in terms of the initiation of necroptosis. On the other hand, it is important to remember that like other types of programmed cell death, necroptosis plays an important role for the organism, as it induces a strong immune response and is involved in the control of cancerogenesis. In this review, we provide an overview of the complex role of necroptosis as an important pathogenetic component of neuronal and astrocyte death in neurodegenerative diseases, epileptogenesis, and ischemic brain damage.

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An emerging role of astrocytes in aging/neuroinflammation and gut-brain axis with consequences on sleep and sleep disorders

Cited by 25 publications

References 288 publications

MMCCI: multimodal integrative analysis of single-cell and spatial cell-type communications to uncover overarching and condition-specific ligand-receptor interaction pathways

MMCCI: multimodal integrative analysis of single-cell and spatial cell-type communications to uncover overarching and condition-specific ligand-receptor interaction pathways

Unravelling the Collective Calcium Dynamics of Physiologically Aged Astrocytes under a Hypoxic State In Vitro

Necroptosis in CNS diseases: Focus on astrocytes

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