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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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-12-01
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| Series: | Frontiers in Aging Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2021.766306/full |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-17T10:46:54Z |
| format | Article |
| id | doaj.art-1967aad2ba50444993be67ee6f81dcf4 |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-12-17T10:46:54Z |
| publishDate | 2021-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-1967aad2ba50444993be67ee6f81dcf42022-12-21T21:52:06ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652021-12-011310.3389/fnagi.2021.766306766306Senescence in Primary Rat Astrocytes Induces Loss of the Mitochondrial Membrane Potential and Alters Mitochondrial Dynamics in Cortical NeuronsSandra Lizbeth Morales-Rosales0Sandra Lizbeth Morales-Rosales1Roberto Santín-Márquez2Roberto Santín-Márquez3Pedro Posadas-Rodriguez4Pedro Posadas-Rodriguez5Ruth Rincon-Heredia6Teresa Montiel7Raúl Librado-Osorio8Armando Luna-López9Nadia Alejandra Rivero-Segura10Claudio Torres11Agustina Cano-Martínez12Alejandro Silva-Palacios13Paulina Cortés-Hernández14Julio Morán15Lourdes Massieu16Mina Konigsberg17Posgrado Biología Experimental, Universidad Autónoma Metropolitana, Mexico City, MexicoDepartamento de Ciencias de la Salud, Universidad Autónoma Metropolitana, Mexico City, MexicoPosgrado Biología Experimental, Universidad Autónoma Metropolitana, Mexico City, MexicoDepartamento de Ciencias de la Salud, Universidad Autónoma Metropolitana, Mexico City, MexicoPosgrado Biología Experimental, Universidad Autónoma Metropolitana, Mexico City, MexicoDepartamento de Ciencias de la Salud, Universidad Autónoma Metropolitana, Mexico City, MexicoInstituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, MexicoInstituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, MexicoDepartamento de Investigación Básica, Instituto Nacional de Geriatría, Mexico City, MexicoDepartamento de Investigación Básica, Instituto Nacional de Geriatría, Mexico City, MexicoDepartamento de Investigación Básica, Instituto Nacional de Geriatría, Mexico City, MexicoDepartment of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, United StatesDepartamento de Fisiología, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, MexicoDepartamento de Biomedicina Cardiovascular, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, MexicoInstituto Mexicano del Seguro Social, Centro de Investigación Biomédica de Oriente, Atlixco, MexicoInstituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, MexicoInstituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, MexicoDepartamento de Ciencias de la Salud, Universidad Autónoma Metropolitana, Mexico City, MexicoThe 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.https://www.frontiersin.org/articles/10.3389/fnagi.2021.766306/fullastrocytecellular senescenceredox stateagingmitochondria |
| spellingShingle | 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 Frontiers in Aging Neuroscience astrocyte cellular senescence redox state aging mitochondria |
| title | 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_short | 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 |
| topic | astrocyte cellular senescence redox state aging mitochondria |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2021.766306/full |
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