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Front Mol Neurosci. 2017 Oct 24;10:330. doi: 10.3389/fnmol.2017.00330. eCollection 2017.

Estradiol Uses Different Mechanisms in Astrocytes from the Hippocampus of Male and Female Rats to Protect against Damage Induced by Palmitic Acid.

Frontiers in molecular neuroscience

Laura M Frago, Sandra Canelles, Alejandra Freire-Regatillo, Pilar Argente-Arizón, Vicente Barrios, Jesús Argente, Luis M Garcia-Segura, Julie A Chowen

Affiliations

  1. Departamento de Pediatría, Universidad Autónoma de Madrid, Madrid, Spain.
  2. Departamento de Endocrinología, Hospital Infantil Universitario Niño Jesús, Madrid, Spain.
  3. Instituto de Investigación Sanitaria Princesa, Madrid, Spain.
  4. Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain.
  5. IMDEA Food Institute, Universidad Autónoma de Madrid, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.
  6. Instituto Cajal, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.
  7. CIBER de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Madrid, Spain.

PMID: 29114202 PMCID: PMC5660686 DOI: 10.3389/fnmol.2017.00330

Abstract

An excess of saturated fatty acids can be toxic for tissues, including the brain, and this has been associated with the progression of neurodegenerative diseases. Since palmitic acid (PA) is a free fatty acid that is abundant in the diet and circulation and can be harmful, we have investigated the effects of this fatty acid on lipotoxicity in hippocampal astrocytes and the mechanism involved. Moreover, as males and females have different susceptibilities to some neurodegenerative diseases, we accessed the responses of astrocytes from both sexes, as well as the possible involvement of estrogens in the protection against fatty acid toxicity. PA increased endoplasmic reticulum stress leading to cell death in astrocytes from both males and females. Estradiol (E2) increased the levels of protective factors, such as Hsp70 and the anti-inflammatory cytokine interleukin-10, in astrocytes from both sexes. In male astrocytes, E2 decreased pJNK, TNFα, and caspase-3 activation. In contrast, in female astrocytes E2 did not affect the activation of JNK or TNFα levels, but decreased apoptotic cell death. Hence, although E2 exerted protective effects against the detrimental effects of PA, the mechanisms involved appear to be different between male and female astrocytes. This sexually dimorphic difference in the protective mechanisms induced by E2 could be involved in the different susceptibilities of males and females to some neurodegenerative processes.

Keywords: astrocytes; endoplasmic reticulum stress; estradiol; hippocampus; palmitic acid

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