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

The decline in brain function during aging is one of the most critical health problems nowadays. Although senescent astrocytes have been found in old-age brains and neurodegenerative diseases, their impact on the function of other cerebral cell types is unknown. The aim of this study was to evaluate...

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Autores principales:	Sandra Lizbeth Morales-Rosales, Roberto Santín-Márquez, Pedro Posadas-Rodriguez, Ruth Rincon-Heredia, Teresa Montiel, Raúl Librado-Osorio, Armando Luna-López, Nadia Alejandra Rivero-Segura, Claudio Torres, Agustina Cano-Martínez, Alejandro Silva-Palacios, Paulina Cortés-Hernández, Julio Morán, Lourdes Massieu, Mina Konigsberg
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	astrocyte cellular senescence redox state aging mitochondria Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/1967aad2ba50444993be67ee6f81dcf4
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spelling	oai:doaj.org-article:1967aad2ba50444993be67ee6f81dcf42021-12-02T00:28:36ZSenescence in Primary Rat Astrocytes Induces Loss of the Mitochondrial Membrane Potential and Alters Mitochondrial Dynamics in Cortical Neurons1663-436510.3389/fnagi.2021.766306https://doaj.org/article/1967aad2ba50444993be67ee6f81dcf42021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fnagi.2021.766306/fullhttps://doaj.org/toc/1663-4365The decline in brain function during aging is one of the most critical health problems nowadays. Although senescent astrocytes have been found in old-age brains and neurodegenerative diseases, their impact on the function of other cerebral cell types is unknown. The aim of this study was to evaluate the effect of senescent astrocytes on the mitochondrial function of a neuron. In order to evaluate neuronal susceptibility to a long and constant senescence-associated secretory phenotype (SASP) exposure, we developed a model by using cellular cocultures in transwell plates. Rat primary cortical astrocytes were seeded in transwell inserts and induced to premature senescence with hydrogen peroxide [stress-induced premature senescence (SIPS)]. Independently, primary rat cortical neurons were seeded at the bottom of transwells. After neuronal 6 days in vitro (DIV), the inserts with SIPS-astrocytes were placed in the chamber and cocultured with neurons for 6 more days. The neuronal viability, the redox state [reduced glutathione/oxidized glutathione (GSH/GSSG)], the mitochondrial morphology, and the proteins and membrane potential were determined. Our results showed that the neuronal mitochondria functionality was altered after being cocultured with senescent astrocytes. In vivo, we found that old animals had diminished mitochondrial oxidative phosphorylation (OXPHOS) proteins, redox state, and senescence markers as compared to young rats, suggesting effects of the senescent astrocytes similar to the ones we observed in vitro. Overall, these results indicate that the microenvironment generated by senescent astrocytes can affect neuronal mitochondria and physiology.Sandra Lizbeth Morales-RosalesSandra Lizbeth Morales-RosalesRoberto Santín-MárquezRoberto Santín-MárquezPedro Posadas-RodriguezPedro Posadas-RodriguezRuth Rincon-HerediaTeresa MontielRaúl Librado-OsorioArmando Luna-LópezNadia Alejandra Rivero-SeguraClaudio TorresAgustina Cano-MartínezAlejandro Silva-PalaciosPaulina Cortés-HernándezJulio MoránLourdes MassieuMina KonigsbergFrontiers Media S.A.articleastrocytecellular senescenceredox stateagingmitochondriaNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENFrontiers in Aging Neuroscience, Vol 13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	astrocyte cellular senescence redox state aging mitochondria Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	astrocyte cellular senescence redox state aging mitochondria Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Sandra Lizbeth Morales-Rosales Sandra Lizbeth Morales-Rosales Roberto Santín-Márquez Roberto Santín-Márquez Pedro Posadas-Rodriguez Pedro Posadas-Rodriguez Ruth Rincon-Heredia Teresa Montiel Raúl Librado-Osorio Armando Luna-López Nadia Alejandra Rivero-Segura Claudio Torres Agustina Cano-Martínez Alejandro Silva-Palacios Paulina Cortés-Hernández Julio Morán Lourdes Massieu Mina Konigsberg Senescence in Primary Rat Astrocytes Induces Loss of the Mitochondrial Membrane Potential and Alters Mitochondrial Dynamics in Cortical Neurons
description	The decline in brain function during aging is one of the most critical health problems nowadays. Although senescent astrocytes have been found in old-age brains and neurodegenerative diseases, their impact on the function of other cerebral cell types is unknown. The aim of this study was to evaluate the effect of senescent astrocytes on the mitochondrial function of a neuron. In order to evaluate neuronal susceptibility to a long and constant senescence-associated secretory phenotype (SASP) exposure, we developed a model by using cellular cocultures in transwell plates. Rat primary cortical astrocytes were seeded in transwell inserts and induced to premature senescence with hydrogen peroxide [stress-induced premature senescence (SIPS)]. Independently, primary rat cortical neurons were seeded at the bottom of transwells. After neuronal 6 days in vitro (DIV), the inserts with SIPS-astrocytes were placed in the chamber and cocultured with neurons for 6 more days. The neuronal viability, the redox state [reduced glutathione/oxidized glutathione (GSH/GSSG)], the mitochondrial morphology, and the proteins and membrane potential were determined. Our results showed that the neuronal mitochondria functionality was altered after being cocultured with senescent astrocytes. In vivo, we found that old animals had diminished mitochondrial oxidative phosphorylation (OXPHOS) proteins, redox state, and senescence markers as compared to young rats, suggesting effects of the senescent astrocytes similar to the ones we observed in vitro. Overall, these results indicate that the microenvironment generated by senescent astrocytes can affect neuronal mitochondria and physiology.
format	article
author	Sandra Lizbeth Morales-Rosales Sandra Lizbeth Morales-Rosales Roberto Santín-Márquez Roberto Santín-Márquez Pedro Posadas-Rodriguez Pedro Posadas-Rodriguez Ruth Rincon-Heredia Teresa Montiel Raúl Librado-Osorio Armando Luna-López Nadia Alejandra Rivero-Segura Claudio Torres Agustina Cano-Martínez Alejandro Silva-Palacios Paulina Cortés-Hernández Julio Morán Lourdes Massieu Mina Konigsberg
author_facet	Sandra Lizbeth Morales-Rosales Sandra Lizbeth Morales-Rosales Roberto Santín-Márquez Roberto Santín-Márquez Pedro Posadas-Rodriguez Pedro Posadas-Rodriguez Ruth Rincon-Heredia Teresa Montiel Raúl Librado-Osorio Armando Luna-López Nadia Alejandra Rivero-Segura Claudio Torres Agustina Cano-Martínez Alejandro Silva-Palacios Paulina Cortés-Hernández Julio Morán Lourdes Massieu Mina Konigsberg
author_sort	Sandra Lizbeth Morales-Rosales
title	Senescence in Primary Rat Astrocytes Induces Loss of the Mitochondrial Membrane Potential and Alters Mitochondrial Dynamics in Cortical Neurons
title_short	Senescence in Primary Rat Astrocytes Induces Loss of the Mitochondrial Membrane Potential and Alters Mitochondrial Dynamics in Cortical Neurons
title_full	Senescence in Primary Rat Astrocytes Induces Loss of the Mitochondrial Membrane Potential and Alters Mitochondrial Dynamics in Cortical Neurons
title_fullStr	Senescence in Primary Rat Astrocytes Induces Loss of the Mitochondrial Membrane Potential and Alters Mitochondrial Dynamics in Cortical Neurons
title_full_unstemmed	Senescence in Primary Rat Astrocytes Induces Loss of the Mitochondrial Membrane Potential and Alters Mitochondrial Dynamics in Cortical Neurons
title_sort	senescence in primary rat astrocytes induces loss of the mitochondrial membrane potential and alters mitochondrial dynamics in cortical neurons
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/1967aad2ba50444993be67ee6f81dcf4
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Senescence in Primary Rat Astrocytes Induces Loss of the Mitochondrial Membrane Potential and Alters Mitochondrial Dynamics in Cortical Neurons

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