Senescence in Primary Rat Astrocytes Induces Loss of the Mitochondrial Membrane Potential and Alters Mitochondrial Dynamics in Cortical Neurons
Por:
Morales-Rosales, Sandra Lizbeth, Santin-Marquez, Roberto, Posadas-Rodriguez, Pedro, Rincon-Heredia, Ruth, Montiel, Teresa, Librado-Osorio, Raul, Luna-Lopez, Armando, Rivero-Segura, Nadia Alejandra, Torres, Claudio, Cano-Martinez, Agustina, Silva-Palacios, Alejandro, Cortes-Hernandez, Paulina, Moran, Julio, Massieu, Lourdes, Konigsberg, Mina
Publicada:
1 dic 2021
Resumen:
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.
Filiaciones:
Morales-Rosales, Sandra Lizbeth:
Univ Autonoma Metropolitana, Posgrad Biol Expt, Mexico City, DF, Mexico
Univ Autonoma Metropolitana, Dept Ciencias Salud, Mexico City, DF, Mexico
Santin-Marquez, Roberto:
Univ Autonoma Metropolitana, Posgrad Biol Expt, Mexico City, DF, Mexico
Univ Autonoma Metropolitana, Dept Ciencias Salud, Mexico City, DF, Mexico
Posadas-Rodriguez, Pedro:
Univ Autonoma Metropolitana, Posgrad Biol Expt, Mexico City, DF, Mexico
Univ Autonoma Metropolitana, Dept Ciencias Salud, Mexico City, DF, Mexico
Rincon-Heredia, Ruth:
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Mexico City, DF, Mexico
Montiel, Teresa:
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Mexico City, DF, Mexico
Librado-Osorio, Raul:
Inst Nacl Geriatr, Dept Invest Basica, Mexico City, DF, Mexico
Luna-Lopez, Armando:
Inst Nacl Geriatr, Dept Invest Basica, Mexico City, DF, Mexico
Rivero-Segura, Nadia Alejandra:
Inst Nacl Geriatr, Dept Invest Basica, Mexico City, DF, Mexico
Torres, Claudio:
Drexel Univ, Coll Med, Dept Neurobiol & Anat, Philadelphia, PA 19104 USA
Cano-Martinez, Agustina:
Inst Nacl Cardiol Ignacio Chavez, Dept Fisiol, Mexico City, DF, Mexico
Silva-Palacios, Alejandro:
Inst Nacl Cardiol Ignacio Chavez, Dept Biomed Cardiovasc, Mexico City, DF, Mexico
Cortes-Hernandez, Paulina:
Ctr Invest Biomed Oriente, Inst Mexicano Seguro Social, Atlixco, Mexico
Moran, Julio:
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Mexico City, DF, Mexico
Massieu, Lourdes:
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Mexico City, DF, Mexico
Konigsberg, Mina:
Univ Autonoma Metropolitana, Dept Ciencias Salud, Mexico City, DF, Mexico
Green Published, gold, Gold, Green
|