Senescence in Primary Rat Astrocytes Induces Loss of the Mitochondrial Membrane Potential and Alters Mitochondrial Dynamics in Cortical Neurons

Morales-Rosales, Sandra Lizbeth; Santín-Márquez, Roberto; Posadas-Rodríguez, Pedro; Rincón-Heredia, Ruth; Montiel, Teresa; Librado-Osorio, Raúl; Luna–López, Armando; Rivero-Segura, Nadia Alejandra; Torres, Claudio; Cano-Martı́nez, Agustina; Silva-Palacios, Alejandro; Cortés-Hernández, Paulina; Morán, Julio; Massieu, Lourdes; Königsberg, Mina

doi:10.3389/fnagi.2021.766306

Cited by 13 publications

(6 citation statements)

References 52 publications

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“…This deregulated glutamate metabolism in senescent astrocytes is a common feature of NDs (Figure 5) [207]. It was also shown that senescent astrocytes decreased neuronal mitochondrial membrane potential and altered neuronal mitochondria functionality after being cocultured with neurons [175]. The authors suggested that this could be due to the fact that senescent astrocytes either lost their ability to secrete factors required for the proper function of neurons or that they gained neurotoxic effect through the secretion of SASP factors [175].…”

Section: Senescent Astrocytes and Age-related Neurodegenerative Diseasesmentioning

confidence: 96%

“…Due to their proliferative capacity, astrocytes also undergo cellular senescence that Cohen et al, named as "astrosenescence" [174]. Numerous studies show that astrocytes can display senescence after exhausted replication, oxidative stress, proteasome inhibition, high glucose, HIV infection, X radiation, hydrogen peroxide, or in the course of aging [175][176][177]. In contrast to reactive astrogliosis, the cellular senescence of astrocytes is a permanent state [174].…”

Section: Morphological and Molecular Features Of Senescent Astrocytesmentioning

confidence: 99%

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Reactive and Senescent Astroglial Phenotypes as Hallmarks of Brain Pathologies

Lazic

Balint

Ninković

et al. 2022

IJMS

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Astrocytes, as the most abundant glial cells in the central nervous system, are tightly integrated into neural networks and participate in numerous aspects of brain physiology and pathology. They are the main homeostatic cells in the central nervous system, and the loss of astrocyte physiological functions and/or gain of pro-inflammatory functions, due to their reactivation or cellular senescence, can have profound impacts on the surrounding microenvironment with pathological outcomes. Although the importance of astrocytes is generally recognized, and both senescence and reactive astrogliosis have been extensively reviewed independently, there are only a few comparative overviews of these complex processes. In this review, we summarize the latest data regarding astrocyte reactivation and senescence, and outline similarities and differences between these phenotypes from morphological, functional, and molecular points of view. A special focus has been given to neurodegenerative diseases, where these phenotypic alternations of astrocytes are significantly implicated. We also summarize current perspectives regarding new advances in model systems based on astrocytes as well as data pointing to these glial cells as potential therapeutic targets.

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Section: Senescent Astrocytes and Age-related Neurodegenerative Diseasesmentioning

confidence: 96%

Section: Morphological and Molecular Features Of Senescent Astrocytesmentioning

confidence: 99%

Reactive and Senescent Astroglial Phenotypes as Hallmarks of Brain Pathologies

Lazic

Balint

Ninković

et al. 2022

IJMS

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“…Therefore, the accumulation of ASP+ and Rh123 in the mitochondria may reduce by a senescence-induced decrease in the mitochondrial membrane potential. 24) Thus, a decrease in the mitochondrial membrane potential may partially affect the results of the uptake assay.…”

Section: Gradual Induction Of Sa-β-gal Staining By Long-termmentioning

confidence: 99%

Effect of Replicative Senescence on the Expression and Function of Transporters in Human Proximal Renal Tubular Epithelial Cells

Sanagawa

Hotta

Sezaki

et al. 2022

Biological & Pharmaceutical Bulletin

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In the field of cosmetic research, there is a growing interest in alternatives to animal experiments, such as in vitro models using cultured cells. The trend is spreading to the field of food and drugs. Although various types of cells are used as in vitro models, the effect of cellular senescence on the expression and function of transporters in these models is unclear. In the present study, we examined the effect of replicative senescence (by passage culture) on the expression and function of transporters in renal proximal tubular epithelial cells (RPTECs). The increase in senescence-associated-β-galactosidase (SA-β-gal)-positive cells, cell cycle arrest markers, and senescence-associated secretory phenotype (SASP) markers was associated with an increase in passage numbers of RPTECs. Gene expression of various transporters in RPTEC was also altered. The mRNA level of organic cation transporter 2 decreased most rapidly with passage numbers among the transporters. The uptake of fluorescent cationic substrates in SA-β-gal-positive RPTECs was less than that in SA-β-gal-negative RPTECs. However, these changes in the expression of transporters seem to be significantly different from those observed in rodents and human kidneys in many aspects. As cellular senescence is observed in various situations, especially in RPTECs, it may be necessary to exclude it from toxicological and pharmacokinetic evaluations using in vitro models as much as possible. Additionally, when discussing cellular senescence, it is important to note the differences between aging in cells and aging and senescence in individuals.

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“…protein expression in terms of fold changequantitative or semi-quantitativebiogenesis[47]rat testes, leidig cellsfluorescence microscopy of MitoTrackerfluorescence intensitysemi-quantitativebiogenesis[48]rat primary cortical astrocytesmicroscopy, biochemical analyses; Western blottingmitochondria mass; OXPHOS, % relative expression of mt. proteinssemi-quantitativenot tested[49]mouse synaptic boutons of axons; neuronsfluorescence microscopy of MitoTracker; immunogold stainingnormalized to cell area, mitochondria length per length of axon; mean fluorescence (normalized to cell area); mitochondrial areasemi-quantitativenot tested[50]mouse diet-induced fatty liver in C57BL/6J/biochemical analyses; Western blottingCS activity; mt protein: tissue protein; TG contentsemi-quantitativenot tested[51]mouse astrocytes cultured cellsfluorescence microscopy of MitoTrackerfluorescence intensitysemi-quantitativenot tested[52]rat Myc null fibroblastsflow cytometry using MitoTracker and NAOfluorescence intensitysemi-quantitativebiogenesis[53]mouse embryonic fibroblastsflow cytometry analysis; fluorescence microscopy of using MitoTrackerfluorescence intensitysemi-quantitativebiogenesis and mitophagy[54]mouse embryonic fibroblastsflow cytometry analysis; fluorescence microscopy of using MitoTrackerfluorescence intensitysemi-quantitativeautophagy[55]rhesus monkey presynaptic boutonselectron micr...…”

Section: Quantitative Aspect Of Heterogeneity Of Mitochondrial Conten...mentioning

confidence: 99%

Significance of quantitative analyses of the impact of heterogeneity in mitochondrial content and shape on cell differentiation

Agarwala,

Dhabal,

Mitra

2024

Open Biol.

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Mitochondria, classically known as the powerhouse of cells, are unique double membrane-bound multifaceted organelles carrying a genome. Mitochondrial content varies between cell types and precisely doubles within cells during each proliferating cycle. Mitochondrial content also increases to a variable degree during cell differentiation triggered after exit from the proliferating cycle. The mitochondrial content is primarily maintained by the regulation of mitochondrial biogenesis, while damaged mitochondria are eliminated from the cells by mitophagy. In any cell with a given mitochondrial content, the steady-state mitochondrial number and shape are determined by a balance between mitochondrial fission and fusion processes. The increase in mitochondrial content and alteration in mitochondrial fission and fusion are causatively linked with the process of differentiation. Here, we critically review the quantitative aspects in the detection methods of mitochondrial content and shape. Thereafter, we quantitatively link these mitochondrial properties in differentiating cells and highlight the implications of such quantitative link on stem cell functionality. Finally, we discuss an example of cell size regulation predicted from quantitative analysis of mitochondrial shape and content. To highlight the significance of quantitative analyses of these mitochondrial properties, we propose three independent rationale based hypotheses and the relevant experimental designs to test them.

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Senescence in Primary Rat Astrocytes Induces Loss of the Mitochondrial Membrane Potential and Alters Mitochondrial Dynamics in Cortical Neurons

Cited by 13 publications

References 52 publications

Reactive and Senescent Astroglial Phenotypes as Hallmarks of Brain Pathologies

Reactive and Senescent Astroglial Phenotypes as Hallmarks of Brain Pathologies

Effect of Replicative Senescence on the Expression and Function of Transporters in Human Proximal Renal Tubular Epithelial Cells

Significance of quantitative analyses of the impact of heterogeneity in mitochondrial content and shape on cell differentiation

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